WO1988000197A1

WO1988000197A1 - Benzopyran and benzothiopyran derivatives and compositions containing them

Info

Publication number: WO1988000197A1
Application number: PCT/HU1987/000027
Authority: WO
Inventors: Rezso^" BOGNA^´R; Csaba JA^´SZBERE^´NYI; Sándor MAKLEIT; András FODOR; Péter DEA^´K; Tibor TIMA^´R
Original assignee: Alkaloida Vegye^´Szeti Gya^´R
Priority date: 1986-06-26
Filing date: 1987-06-24
Publication date: 1988-01-14
Also published as: HU197331B; EP0271550A1; JPH01500429A; ES2006521A6

Abstract

The compounds of general formula (I), wherein R1, R2, R3, n, Q1 and Q2 are as defined in claim 1 as well as their biologically active salts. The invention also relates to fungicide, nematocide, acaricide, bactericide and insecticide compositions containing the compounds of general formula (I) as active ingredients as well as to the process for the preparation of these compounds and compositions.

Description

Benzopyran and benzothiopyran derivatives and compositions containing them

The inven t ion relates to novel benzopyran, and benzothiopyran derivatives, to their intermediates and to compositions containing the novel benzopyran and benzothiopyran derivatives. The invention also relates to the preparation of these compounds, their intermediates and of the compositions containing the novel benzopyran and benzothiopyran derivatives; furthermore, the invention relates to the use of these compositions against nematodes, insects, worms and the like.

In 1976, Bowers et al. [Science 193, 542 (1976)] reported on the isolation of the anti-juvenile hormones of plant origin which were active against insects. After this publication, an intense resea rch was worldwide started in order to obtain compounds surpassing the activity of the two original precocenes, i.e. precocene 1 of formula (A) and precocone 2 of formula (B). During the study on the action mechanism and structure-activity relations, several recognitions arose which promoted the further synthetic work (e.g. G. T. Brooks: Gen. Pharmac. 8, 221 (1977); K. Slama: Acta Entomol. Bohemoslov. 75, 65 (1978), etc.].

The novel benzopyran and benzothiopyran derivatives of the present invention have the general formula (I),

(I)

where in

R¹ and R² are independently from each other hydrogen, an unsubstituted or optionally suitably substituted alkyl or aryl group; or

R¹ and R² together may be a cycloalkyl group;

R³ is hydrogen; an optionally protected hydroxyl group; an alkyl, alkoxy, O-trialkyltin group; a phosphoric acid, thiophosphoric acid or phosphorous acid alkyl or aryl ester group connected through the oxygen atom; an acyloxy, acyloxyalkoxy, O-trialkylsilyl, aryloxy, alkenyloxy, alkynyloxy, cycloalkyloxy, cyclo- alkenyloxy, cycloalkylalkoxy group; an acyloxy or alkoxy group substituted by phosphoric acid, phosphonic acid or their esters; or two adjacent R³ groups together may represent: an -O-(CH₂)_m-O-group, wherein m is 1, 2, 3 or 4; or a condensed aromatic ring; or an -O-(CH₂)_m-(O)_z- group, wherein m is as defined above and z is 0 or 1; or an -O-P(Cl)-O-, -O-P(OC₂H₅)-O-, -O-P=O(OC₂H₅)-O-, -O-P=S(OC₂H₅)-O-, -O-(C=O)-O-, -O-(C=S)-O-, -O-P=O(SC₂H₅)-O-, -O-P=S(SC₂H₅)-O- or an -O-(S=O)-O- group; or a halogen or a haloalkyl, nitro, amino or suitably substituted amino group; an alkoxy group substituted by an alkylamino or a dial- kylamino group; or a nitrile, mercapto, optionally substituted alkylthio group; an optionally ring-substituted aralkyloxy group; an acyl group; or two adjacent R groups together may also represent a -C=C-C(=O)-O- and -C=C-C=(CH₃)₂-O- group; n is 0, 1, 2, 3 or 4, and these R³ groups may have, independdntly from each other, any meaning defined for the R³ groups, Q¹ is oxygen, sulfur, SO or SO₂; Q² is sulfur or selenium.

The compounds of the general formula (I) are new; simultaneously, they contain each structural moieties of the original precocene 1 and precocene 2 molecules which are essential for the biological activity. However, the biotransformation-sensitive double bond is preferably in a protected form.

According to an other aspect of the invention, there is provided a process for the preparation of the novel compounds of the general formula (I) and salts thereof, which comprises a) reacting a compound of the general formula (II),

(II)

wherein Q¹ R¹, R², R³ and n are as defined above, with a compound of the general formula (III),

H₂N-NH-R⁴ (III)

wherein R⁴ means hydrogen, CO-alkyl, CO-aryl, COO-alkyl, COO-aryl, CONH₂, CSNH₂, CONHNH₂, CSNHNH₂, CNHNH₂, CNHNHNH₂, SO₂-alkyl or SO₂-aryl group, and reacting the thus-obtained compound of the general formula (IV), ( IV )

wherein R¹, R² , R³, R⁴, Q¹ and n are as defined above, with selenium dioxide in order to obtain a compound of the general formula (I), wherein

Q² is selenium (as shown in scheme a);

U

or b) reacting a compound of the general formula (V)

(V)

wherein R¹, R² , R³, R⁴ and n are as defined above, with an acid and then with selenium dioxide to obtain a compound of the general formula (I), wherein Q¹ is oxygen and Q² is selenium (as shown in scheme b);

(b)

or c) reacting a compound of the general formula (VI)

(VI)

wherein R¹, R² , R³, Q¹, Q² and n are as defined above, with a diazo-transfer reagent in the presence of a base (as shown in scheme c);

(c)

or d) reacting a compound of the general formula (VII) (VII)

wherein R¹, R² , R³, Q² and n are as defined above, with acetic acid in order to obtain a compound of the general formula (I), wherein Q¹ is oxygen (as shown in scheme d);

(d)

VII

or e) treating a compound of the general formula (VIII)

(VIII)

wherein R¹, R² , R³, Q¹, Q² and n are as defined above and R⁵ means an alkyl, aryl, alkylamino or arylamino group, with a base (as shown in scheme e);

(e)

or f) reacting a compound of the general formula (IX),

(IX)

wherein R³, Q¹, Q² and n are as defined above, with a Grignard reagent of the general formula

R¹MgX and/or R²MgX, wherein R¹ and R² are as defined above and X is halogen, or with a metal alkyl compound (as shown in scheme f) ( f )

IX

and, if desired, oxidizing a thus-obtained compound of the general formula (I), wherein Q¹ is sulfur, to a compound of the general formula (I) wherein Q¹ is an SO or SO₂ group and/or, if desired, converting a compound of the general formula (I) to the salt thereof.

The cyclization of the semicarbazones according to the process a) is known [I. Lalezari, A. Shafiee: Tetrahedron Lett. 5105 (1969); I. Lalezari, A. et al.: Angew. Chem. 82 , 484 (1970); I. Lalezari et al.: J . Org. Chem. 36, 2836 (1971)]. However, these reactions were not extended to the preparation of systems involving more fused heterocycles. The ring systems of the compounds of the invention are new.

A part of semicarbazones having the general formula (II) used as starting substances are also novel compounds.

For carrying out the cyclization selenium dioxide, selenous acid or selenous acid derivatives (e.g. salts) or selenium oxychloride are used in the presence of C_{1- 6} aliphatic carboxylic acids or their mixtures or the mixtures of these acids with suitable selected solvents or in suspensions prepared therefrom. In the most cases, an equimolar amount of 1.1 to 1.3 equivalents of the selenium compound are used for oxidation. The reaction is usually carried out at a temperature of 0 to 120 °C, preferably at 30 to 80 °C.

At the end of the mostly unidirectional reaction, the product is obtained by evaporation, whereby the solvent used for the reaction can be recyclized into the process.

An important part of the substituted or unsubstituted hydrazones, thiosemicarbazones, guanylhydrazones, bis-carbohydrazones or bis-thiocarbohydrazones used as starting substances in process b) are also novel compounds. Thus, the invention also relates to the compounds of the general formulae (V), (X)

(X)

and (XI)

(XI)

as well as to the preparation of these compounds. Similarly to the process a), the cyclizing reaction is accomplished by using selenium dioxide, selenous acid or selenium oxychloride. The selenium- containing reagent is preferably used in an amount of 1.0 to 1.5 equivalents and optionally given in several portions to the compound to be cyclized. This reaction is usually carried out at 0 to 120 ºC, preferably between 20 °C and 80 °C. The product is separated by evaporating or pouring the reaction mixture into water optionally followed by extraction.

According to process c) , a compound o f the general formula ( VI ) i s reacted with a suitably selected diazo-transfer reagent [M. Regitz: Recent Synthetic Methods in Diazo Chemistry, Synthesis 1972, 351].

In the process d), a compound of the general formula (VII) is cyclized according to the first step of process b), i.e. by using an aliphatic carboxylic acid or an inorg anic acid , opt ion ally in a miscible solvent under heating.

In process e), the cyclization is carried out by treating a compound of the general formula (VIII) with a base. The ring closure proceeds through a non- -isolated intermediate.

According to process f) of the invention, a compound of the general formula (IX) is reacted with an R¹MgX or R²MgX Grignard reagent. This method is well known in the chemistry of coumarins [J. Houben: Chem. Ber. 37, 489 (1904)] which has been investigated in detail [H. Decker and T. Fellenberg: Liebigs Ann. Chem. 356, 281 (1907); R. L. Shriner and A. G. Sharp.: 3 . Org. Chem. 4, 575 (1939); L. I. Smith and P. M. Rouff: 3 . Amer. Chem. Soc. 62, 145 (1940)] and is also being used today [H. P. Pommier et al.: Can. J. Chem. 51, 1377 (1979); M. V. Naidu and G. S. Krishna-Rao: Proc. Ind. Acad. Sci. 88, 197 (1979)].

A particularly preferred but not exclusive use of the above substituents is as follows: 4-Phenyl-4H-selenadiazolo[5,4-c][1]benzopyran, 4-phenyl-4H-selenadiazolo[5,4-c][1]benzothiopyran, 4-phenyl-4H-selenadiazolo[5,4-c][1]bentzhoiopyran-5-oxide, 4-phenyl-4H-selenadiazolo[5,4-c][1]bentzhoiopyran-5,5-dioxide, 4-phenyl-4H-thiadiazolo[5,4-c][1]benzopyran, 4-phenyl-4H-thiadiazolo[5,4-c][1]benzothiopyran,

4-phenyl-4H-thiadiazolo[5,4-c][1]benzothiopyran-5-oxide, 4-phenyl-4H-thiadiazolo[5,4-c][1]benzothiopyran-5,5- -dioxide, 4H-selenadiazolo[5,4-c][1]benzopyran, 4H-selenadiazolo[5,4-c][1]benzothiopyran,

4H-selenadiazolo[5,4-c][1]benzothiopyran-5-oxide, 4H-selenadiazolo[5,4-c][1]benzothiopyran-5,5-dioxide, 4,4-dimethyl-7-methoxy-4H-selenadiazolo[5,4-c][1]benzo- pyran, 4,4-dimethyl-7-methoxy-4H-selenadiazolo[5,4-c][1]benzo- thiopyran,

4,4-dimethyl-7-methoxy-4H-selenadiazolo[5,4-c][1]benzo- thiopyran-5-oxide, 4,4-dimethyl-7-methoxy-4H-selenadiazolo[5,4-c][1]benzo- thiopyran-5,5-dioxide,

4H-thiadiazolo[5,4-c][1]benzopyran, 4H-thiadiazolo[5,4-c][1]benzothiopyran, 4H-thiadiazolo[5,4-c][1]benzothiopyran-5-oxide, 4H-thiadiazolo[5,4-c][1]benzothiopyran-5,5-dioxide, 4,4-dimethyl-7-methoxy-4H-thiadiazolo[5,4-c][1]benzo- pyran,

4,4-dimethyl-7-methoxy-4H-thiadiazolo[5,4-c][1]benzo- thiopyran, 4,4-dimethyl-7-methoxy-4H-thiadiazolo[5,4-c][1]benzo- thiopyran-5-oxide,

4,4-dimethyl-7-methoxy-4H-thiadiazolo[5,4-c][1]benzo- thiopyran-5,5-dioxide,

7,8-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]-benzopyran, 7,8-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzothiopyran, 7,8-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]-benzothiopyran-5-oxide, 7,8-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]-benzothiopyran-5,5-dioxide, 7,8-dimethoxy-4,4-dimethyl-4H-thiadiazolo[ 5 , 4 -c ][ 1]b en zo-pyran, 7,8-dimethoxy-4,4-dimethyl-4H-thiadiazolo[ 5 , 4 -c ][ 1]b en zo-thiopyran, 7,8-dimethoxy-4,4-dimethyl-4H-thiadiazolo[5,4-c][1]benzo-thIopyran-5-oxide, 7,8-dimethoxy-4,4-dimethyl-4H-thiadiazolo[5,4-c][1]benzo-thiopyran-5,5-dioxide, 4,4-dimethyl-7-ethoxy-8-methoxy-4H-selenadiazolo[5,4-c]-[1]benzopyran, 4,4-dimethyl-7-ethoxy-8-methoxy-4H-selenadiazolo[5,4-c]-[1]benzothiopyran, 4,4-dimethyl-7-ethoxy-8-methoxy-4H-selenadiazolo[5,4-c]-[1]benzothiopyran-5-oxide, 4,4-dimethyl-7-ethoxy-8-methoxy-4H-selenadiazolo[5,4-c]-[1]benzothiopyran-5,5-dioxide, 4,4-dimethyl-7-ethoxy-8-methoxy-4H-thiadiazolo[5,4-c]-[1]benzopyran, 4,4-dimethyl-7-ethoxy-8-methoxy-4H-thiadiazolo[5,4-c]-[1]benzothiopyran, 4,4-dimethyl-7-ethoxy-8-methoxy-4H-thiadiazolo[5,4-c]-[1]benzothiopyran-5-oxide, 4,4-dimethyl-7-ethoxy-8-methoxy-4H-thiadiazolo[5,4-c]-[1]benzothiopyran-5,5-dioxide, 4,4-dimethyl-8-ethoxy-7-methoxy-4H-selenadiazolo[5,4-c]-[1]benzopyran, 4,4-dimethyl-8-ethoxy-7-methoxy-4H-selenadiazolo[5,4-c]-[1]benzothiopyran, 4,4-dimethyl-8-ethoxy-7-methoxy-4H-selenadiazolo[5,4-c]-[1]benzothiopyran-5-oxide, 4,4-dimethyl-8-ethoxy-7-methoxy-4H-selenadiazolo[5,4-c]-[1]benzothIopyran-5,5-dioxide, 4,4-dimethyl-8-ethoxy-7-methoxy-4H-thiadiazolo[5,4-c]- [1]benzopyran, 4,4-dimethyl-8-ethoxy-7-methoxy-4H-thiadiazolo[5,4-c][1]- benzothiopyran, 4,4-dimethyl-8-ethoxy-7-methoxy-4H-thiadiazolo[5,4-c]- [1]benzothiopyran-5-oxide, 4,4-dimethyl-8-ethoxy-7-methoxy-4H-thiadiazolo[5,4-c][1]- benzothiopyran-5,5-dioxide, 4,4-dimethyl-7-(2',2',2'-trifluoroethoxy)-4H-selena- diazolo[5,4-c][1]benzopyran, 4,4-dimethyl-7-(2',2',2'-trifluoroethoxy)-4H-selena- diazolo[5,4-c][1]benzothiopyran, 4,4-dimethyl-7-(2',2',2'-trifluoroethoxy)-4H-selena- diazolo[5,4-c][1]benzothiopyran-5-oxide, 4,4-dimethyl-7-(2',2',2'-trifluoroethoxy)-4H-selena- diazolo[5,4-c][1]benzothiopyran-5,5-dioxide, 7,8-diethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, 4,4-dimethyl-7-ethoxy-4H-selenadiazolo[5,4-c][1]benzo-pyran, 4,4-dimethyl-7-propoxy-4H-selenadiazolo[5,4-c][1]benzo¬pyran, 4,4-dimethyl-7-isopropoxy-4H-selenadiazolo[5,4-c][1]-benzopyran, 7-n-butoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]benzo¬pyran, 7-sec.-butoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]-benzopyran, 4,4-dimethyl-7-isobutoxy-4H-selenadiazolo[5,4-c][1]-benzopyran, 7-amyloxy-4,4-dimethyl-4--selenadiazolo[5,4-c][1]benzo-pyran, 4,4-dimethyl-7-n-octyloxy-4H-selenadiazolo[5,4-c][1]-benzopyran, 4,4-dimethyl-7-n-dodecyloxy-4H-selenadiazolo[5,4-c][1]-benzopyran, 4,4-dimethyl-7-n-octadecyloxy-4H-selenadiazolo[5,4-c]-[1]benzopyran, 4,4-dimethyl-7-(methoxy)methoxy-4H-selenadiazolo[5,4-c]-[1]benzopyran, 7-cyclopropyloxy-4,4-dimethyl-4H-selenadiazolo[5,4-c]-[1]benzopyran, 7-cyclobutyloxy-4,4-dimethyl-4H-selenadiazolo[5,4-c]-[1]benzopyran, 7-cyclopentyloxy-4,4-dimethyl-4H-selenadiazolo[5,4-c]-[1]benzopyran, 7-cyclohexyloxy-4,4-dimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran, 7-benzyloxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]ben-zopyran, 7-(2-chlorobenzyloxy)-4,4-dimethyl-4H-selenadiazolo[5,4-c]-[1]benzopyran, 7-benzyloxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]-benzothiopyran, 7-(3-chlorobenzyloxy)-4,4-dimethyl-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-(4-chlorobenzyloxy)-4,4-dimethyl-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-(l-naphthylmethoxy)-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-(2,3-dichlorobenzyloxy)-4,4-dimethyl-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-(2,4-dichlorobenzyloxy)-4,4-dimethyl-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-(2-naphthylmethoxy)-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-(l-tetralinyloxy)-4H-selenadiazolo[5,4-c]-[1]benzopyran, 4,4-dimethyl-7-(2-tetralinyloxy)-4H-selenadiazolo[5,4-c]-[1]benzopyran, 4,4-dimethyl-7-hydroxy-4H-seIenadiazolo[5,4-c][1]benzo¬pyran, 7,8-dihydroxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, 4,4-dimethyl-7-hydroxy-4H-selenadiazolo[5,4-c][1]- benzopyran, 7,8-dihydroxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzothiopyran, 7,9-dihydroxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, 6,7-dihydroxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, 4,4-dimethyl-7-hydroxy-6-methoxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, 6,7-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran 7,9-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, 7-allyloxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, 4,4-dimethyl-7-prenyloxy-4H-selenadiazolo[5,4-c][1]- benzopyran, 7-(3-cyclopentenyloxy)-4,4-dimethyl-4H-selenadiazolo- [5,4-c][1]-benzopyran, 7-(3-cyclohexenyloxy)-4,4-dimethyl-4H-selenadiazolo-[5,4-c][1]-benzopyran, 4,4-dimethyl-7-propargyloxy-4H-selenadiazolo[5,4-c][1]-benzopyran, 7-chloro-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]benzo¬pyran, 7-bromo-4,4-dimethyl-4H-selenadiazolo[5,4-c][1[benzo-pyran, 4,4-dimethyl-7-trifluoromethylthio-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-methylthio-4H-selenadiazolo[5,4-c][1]-benzopyran, 4,4-dimethyl-7-ethylthio-4H-selenadiazolo[5,4-c][1]benzo-pyran, 4,4-dimethyl-7-(2',2',2'-trifluoroethylthio)-4H-selena¬diazolo[5,4-c][1]benzopyran, 7-allylthio-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]benzo¬pyran, 4,4-dimethyl-7-propargylthio-4H-selenadiazolo[5,4-c][1]-benzopyran, 4,4-dimethyl-7-prenylthio-4H-selenadiazolo[5,4-c][1]-benzopyran, 4,4-dimethyl-7-propylthio-4H-selenadiazolo[5,4-c][1]-benzopyran, 4,4-dimethyl-7-isopropylthio-4H-selenadiazolo[5,4-c][1]-benzopyran, 7-butylthio-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]-benzopyran, 4,4-dimethyl-7-isobutylthio-4H-selenadiazolo[5,4-c][1]-benzopyran, 7-sec.-butylthio-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]-benzopyran, 4,4-dimethyl-7-(2-dimethylaminoethoxy)-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-(2-dimethylaminoethylthio)-4H-selena-diazolo[5,4-c][1]benzopyran, 7-(2-diethylamInoethylthio)-4,4-dimethyl-4H-selena-diazolo[5,4-c][1]benzopyran, 7-(2-diethylaminoethooy)-4,4-dimethyl-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-(2-pyrrolidInoethoxy)-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-(2-piperidinoethoxy)-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-(2-morpholinoethoxy)-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-(N-methylpiperazinoethoxy)-4H-selena-diazolo[5,4-c][1]benzopyran, 4,4-dimethyl-7-(N-ethylpiperazinoethoxy)-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-(N-benzylpiperazinoethoxy)-4,4-dimethyl-4H-seIenadiazolo[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-(2',2',2'-trifluoroethoxy)- -4H-selenadiazolo[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-propoxy-4H-selenadiazolo[5,4-c]- [1]benzcpyran, 4,4-dimethyl-7-isopropoxy-8-methoxy-4H-selenadiazolo- [5,4-c][1]benzopyran, 7-n-butoxy-4,4-dimethyl-8-methoxy-4H-selenadiazolo- [5,4-c][1]benzopyran, 7-sec.-butoxy-4,4-dimethyl-8-methoxy-4H-selenadiazolo- [5,4-c][1]benzopyran, 4,4-dimethyl-7-isobutoxy-8-methoxy-4H-selenadiazolo- [5,4-c][1]benzopyran, 4,4-dimethyl-7-isobutoxy-8-methoxy-4H-selenadiazolo- [5,4-c][1]benzothiopyran. 7-amyloxy-4,4-dimethyl-8-methoxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, 4,4-dimethyl-8-methoxy-7-n-octyloxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-n-dodecyloxy-8-methoxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-n-octadecyloxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-(methoxy)methoxy-4H-selenadiazolo[5,4-c][1]benzothiopyran, 4,4-dimethyl-8-methoxy-7-methoxyethoxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-cyclopropyloxy-4,4-dimethyl-8-methoxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-cyclopropylmethoxy-4,4-dimethyl-8-methoxy-4H-selena-diazolo[5,4-c][1]benzopyran, 7-cyclobutyloxy-4,4-dimεthyl-8-methoxy-4H-selenadiazolo-[5,4-c][1]benzcpyran, 7-cyclopentyloxy-4,4-dimethyl-8-methoxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-cyclohexyloxy-4,4-dimethyl-8-methoxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-benzyloxy-4,4-dimethyl-8-methoxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-(2-chlorobenzyloxy)-4,4-dimethyl-8-methoxy-4H-selena-diazolc[5,4-c][1]benzopyran, 7-(3-chlorobenzyloxy)-4,4-dimethyl-8-methoxy-4H-selena-diazolo[5,4-c][1]benzopyran, 7-(4-chlorobenzyloxy)-4,4-dimethyI-8-methoxy-4H-selena-diazolo[5,4-c][1]benzopyran, 7-(2,3-dichlorobenzyloxy)-4,4-dimethyl-8-methoxy-4H-selenadiazolo[5,4-c][1]benzopyran, 7-(2,4-dichlorobenzyloxy)-4,4-dimethyl-8-methoxy-4H-selenadiazolo[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-(1-naphthylmethoxy)-4H-selena-diazolo[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-(2-naphthylmethoxy)-4H-selena-diazolo[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-(1-tetralinyloxy)-4H-selena-diazolo[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-(2-tetralinyloxy)-4H-selena-diazolo[5,4-c][1]benzopyran, 4,4-dimethyl-7-hydroxy-8-methoxy-4H-selenadiazolo[5,4-c]-[1]benzopyran, 4,4-dimethyl-7-hydroxy-9-methoxy-4H-selenadiazolo[5,4-c]-[1]benzopyran, 4,4-dimethyl-7-hydroxy-6-methoxy-4H-selenadiazolo[5,4-c]-[1]benzopyran, 7-methoxy-4,4,6-trimethyl-4H-selenadiazolo[5,4-c][1]benzo-pyran, 7-methoxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c][1]benzo-pyran, 7-ethoxy-4,4,6-trimethyl-4H-selenadiazolo[5,4-c][1]benzo-pyran, 7-propargyloxy-4,4,6-trimethyl-4H-seIenadiazolo[5,4-c][1]-benzopyran, 7-ethoxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c][1]benzo¬pyran, 7-propargyloxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c]- [1]-benzopyran, 7-allyloxy-4,4-dimethyl-8-methoxy-4H-selenadiazolo- [5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-prenyloxy-4H-selenadiazolo- [5,4-c][1]benzopyran, 7-(3-cyclopentenyloxy)-4,4-dimethyl-8-methoxy-4H-selena- diazolo[5,4-c][1]benzopyran, 7-(3-cyclohexenyloxy)-4,4-dimethyl-8-methoxy-4H-selena- diazolo[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-propargyloxy-4H-selenadiazolo- [5,4-c][1]benzopyran, 7-chloro-4,4-dimethyl-8-methoxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, 7-bromo-4,4-dimethyl-8-methoxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, 4,4-dimethyl-8-methoxy-7-trifluoromethoxy-4H-selena-diazolo[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-trifluoromethylthio-4H-selena-diazolo[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-methylthio-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-ethylthio-8-methoxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-methylthio-8-(2',2',2'-trifluoroethylthio)- -4H-selenadiazolo[5,4-c7[1]benzopyran, 7-allylthio-4,4-dimethyl-8-methoxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-propargylthio-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-prenylthio-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-8-methoxy-7-propylthio-4H-selenadiazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-isopropylthio-8-methoxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-butylthio-4,4-dimethyl-8-methoxy-4H-selenadIazolo-[5,4-c][1]benzopyran, 4,4-dimethyl-7-isobutylthio-8-methoxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-sec.-butylthio-4,4-dirnethyl-8-methoxy-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-(2-diethylaminoethylthio)-4,4-dimethyl-8-methoxy- -4H-selenadiazolo[5,4-c][1]benzopyran, 4,4-dimethyl-7-tributylstannyloxy-4H-selenadiazolo[5,4-c]-[1]benzopyran, 4,4-dimethyl-8-methoxy-7-tributylstannyloxy-4H-selena-diazolo[5,4-c][1]benzopyran, 7-diethoxyphosphoroyloxy-4,4-dimethyl-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-diethoxyphosphoroyloxy-4,4-dimethyl-8-methoxy-4H-selenadiazolo[5,4-c][1]benzopyran, 4,4-dimethyl-4H-dioxolo[4,5-h]selenadiazolo[5,4-c][1]ben¬zopyran, 4,4-dimethyl-4H-[1,4]-dioxano[2,3-h]selenadiazolo[5,4-c]-[1]benzopyran, 4,4-dimethyl-4H-[1,3[-dioxolo[4,5-g]selenadiazolo[5,4-c]-[1]benzopyran, 4,4-dimethyl-4H-[1,4]-dioxano[2,3-g]seIenadiazolo[5,4-c]-[1]benzopyran, 7-methoxy-5-spirocyclopropyl-4H-selenadiazolo[5,4-c]-[1]benzopyran, 7,8-dimethoxy-4-spirocyclopropyl-4H-selenadiazolo[5,4-c]-[1]benzopyran, 8-ethoxy-7-methoxy-4-spirocyclopropyl-4H-selenadiazolo-[5,4-c][1]benzopyran, 7-ethoxy-8-methoxy-4-spirocyclopropyl-4H-selenadiazolo-[5,4-c][1]benzopyran, 7'-methoxy-spiro[cycloproane-1,4'-(4'H-selenadiazolo-[5,4-c][1]benzopyran)[ spiro[cyclopropane-1,4'-(4'H-[I,3[-dioxolo[4,5-g[selena-diazolo[5,4-c][1]benzopyran)[ spiro[cyclobutane-1,4'-(4'H-[1,3]-dioxolo[4,5-g]selena- diazolo[5,4-c][1]benzopyran], spiro[cyclopropane-1,4'-(4'H-[1,4]-dioxano[2,3-g]selena- diazolo[5,4-c][1]benzopyran)], spiro[cyclopentane-1,4'-(4'H-[1,4]-dioxano[2,3-h]selena- diazolo[5,4-c][1]benzopyran)], spiro[cyclohexan-1,4'-(4'H-[1,3]-dioxoln[4,5-g]selena- diazolo[5,4-c][1]benzopyran, spiro[cyclooctane-1,4'-(4'H-[1,3]-dioxolo[4,5-h]selena- diazolo[5,4-c][1]benzopyran.

The invention is illustrated in detail by the aid of the following non-limiting Examples. The compounds prepared were characterized also by their IR, ¹H-NMR and mass spectra.

Example 1

Preparation of 2,2-dimethyl-7-methoxy-4- -chromanone semicarbazone This compound was prepared or referred to, respectively (W. Bridge et al.: J . Chem. Soc. 1937, 1530)

A mixture containing 8.24 g (40 mmoles) of 2,2-dimethyl-7-methoxy-4-chromanone , 4.8 g of semicarbazide hydrochloride and 5 g of ammonium acetate in 100 ml of ethanol is refluxed for 12 hours, then evaporated and the solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p..: 224-226 °C (literature m.p.: 226 °C). R_f: 0.12 (benzene/ethyl acetate 1:1)

0.41 (toluene /ethyl acetate/formic acid 7:3:1) 0.36 (chloroform/ethanol 9:1) Analysis: Calculated for C₁₃H₁₇N₃O₃ (molecular weight 263) C % = 61,71; H % = 6,77; N % = 16,61; Found: C % = 61,9 ; H % = 6,65; N % = 16,8 ;

Example 2 Preparation of 2,2-dimethyl-6,7-dimethoxy- -4-chromanone semicarbazone A mixture containing 9.44 g (40 mmoles) of 2,2-dimethyI-6,7-dimethoxy-4-chromanone , 4.8 g of semicarbazide hydrochloride and 5 g of ammonium acetate in 100 ml of ethanol are refluxed until the most part of the starting substance has been transformed [as detected by thin layer chromatography (TLC)]. Then, the mixture is evaporated, the solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 208ºC which is useful for the next step without any purification. R_f: 0,07 (benzene/ethyl acetate 1:1)

0,28 (toluene/ethyl acetate/formic acid 7:3:1) 0.35 (chloroform/ethanol 9:1) Analysis:

Calculated for C₁₄H₁₉N₃O₄ (molecular weight: 293) C % = 57.38; H % = 6.53; N % = 14.34;

Found: C % = 57.7 ; H % = 6.4 ; N % = 14.5 ;

Example 3 Preparation of 7-methoxy-2,2,8-trimethyl- -4-chromanone semicarbazone

8.8 g (40 mmoles) of 7-methoxy-2,2,8-trimethyl--4-chromanone , 4.8 g of semicarbazide hydrochloride and 5 g of ammonium acetate are refluxed In 100 ml of ethanol till the transformation of the most part of the starting substance (as detected by TLC). Then, the mixture is evaporated, the solid residue is washed with water and with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 186-188 °C, which is useful for the next step without any purification. R_f = 0.14 (benzene/ethyl acetate = 1:1) 0.47 (toluene/ethyl acetate/formic acid 7:3:1) 0.37 (chloroform/ethyl acetate = 9:1) Analysis:

Calculated for C₁₄H₁₉N₃O₃ (molecular weight: 277) C % = 60.7 ; H % = 6.91; N % = 15.17; Found: C % = 60.9 ; H % = 6.9 ; N % = 15.3 ;

Example 4

Preparation of 7-methoxy-2,2,5-trimethyl- -4-chromanone semicarbazone The process and working up described in

Example 3 are followed, except that 8.8 g (40 mmoles) of 7-methoxy-2,2,5-trimethyl-4-chromanone are used as starting material to give the title compound, m.p.: 220-222 °C. R_f = 0.13 (benzene/ethyl acetate = 1:1)

0.47 (toluene/ethyl acetate/formic acid = 7:3:1) 0.38 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₄H₁₉N₃O₃ (molecular weight: 277) C % = 60.7 ; H % = 6.91; N % = 15.17;

Found: C % = 60.8 ; H % = 6.9 ; N % = 15.2 ;

Example 5

Preparation of 7,8-dimethoxy-2,2-dimethyl- -4-chromanone semicarbazone

9.44 g (40 mmoles) of 7,8-dimethoxy-2,2- -dimethyl-4-chromanone , 4.8 g of semicarbazidehydrochloride and 4 g of ammonium formiate are refluxed in 100 ml of methanol till the transformation of the most part of the starting substance (as detected by TLC). Then, the mixture is evaporated and the solid residue is washed with water to give the title compound, m.p.: 183-185 °C, which is useful for the next step without any purification. R_f = 0.10 (benzene/ethyl acetate = 1:1)

0.30 (toluene/ethyl acetate:formic acid = 7:3:1)

0.35 (chloroform:ethanol = 9:1)

Analysis:

Calculated for C₁₄H₁₉N₃O₄ (molecular weight: 293)

C % = 57.38; H % = 6.53; N % = 14.34; Found: C % = 57.5 ; H % = 6.5 ; N % = 14.5 ;

Example 6

Preparation of 5,7-dimethoxy-2,2-dimethyl- -4-chromanone semicarbazone 9.44 g (40 mmoles) of 5,7-dimethoxy-2,2- dimethyl-4-chromanone are refluxed with 4.8 g of semicarbazide hydrochloride and 5 g of ammonium acetate in 100 ml of n-propanol till the transformation of the most part of the starting substance (as detected by TLC). Then, the mixture is evaporated, the solid residue is washed with water and with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 181-182 °C, which is useful for the next step without any purification. R_f = 0.09 (benzene/ethyl acetate = 1:1) 0.43 (chloroform/ethanol = 9:1)

0.39 (toluene/ethyl acetate/formic acid = 7:3:1) Analysis:

Found: C % = 57.6 ; H % = 6.5 ; N % = 14.4 ;

Example 7

Preparation of 2 ,2-dimethyl-7-ethoxy-4-chroma- none semicarbazone

2.2 g (10 mmoles) of 2,2-dimethyl-7-ethoxy- -4-chromanone are refluxed with 1.2 g of semicarbazide hydrochloride and 1.25 g of ammonium propionate in 25 ml of isopropanol up to the transformation of the most part of the starting substance (as detected by TLC), then the mixture is evaporated, the solid residue is washed with water and dried to give the title compound, m.p.: 183-185 °C, which is useful for cyclization or as intermediate for other reactions, too. R_f = 0.13 (benzene/ethyl acetate 1:1)

0.52 (benzene/ethyl acetate/acetic acid 7:3:1) 0.42 (chloroform/ethanol 9:1) Analysis : Calculated for C₁₄H₁₉N₃O₃ (molecular weight: 277) C % = 60.7 ; H % = 6.91; N % = 15.17;

Found: C % = 60.9 ; H % = 6.8 ; N % = 15.3 ;

Example 8

Preparation of 2,2-dimethyl-7-ethoxy-6-methoxy- -4-chromanone semicarbazone

5.0 g (20 mmoles) of 2,2-dimethyl-7-ethoxy- -6-methoxy-4-chromanone are refluxed with 2.4 g of semicarbazide hydrochloride and 2.5 g of ammonium acetate in 50 ml of ethanol till the transformation of the most part of the starting substance (as detected by TLC), then evaporated and the solid residue is washed with water and with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 205-207 °C, which is useful for the next step without any purification.

R_f = 0.07 (benzene/ethyl acetate 1:1)

0.54 (benzene: ethyl acetate/glacial acetic acid 7:3:1) 0.49 (chloroform:ethanol 9:1) Analysis: Calculated for C₁₅H₂₁N₃O₄ (molecular weight: 307) C % = 58.68; H % = 6.89; N % = 13.69; Found: C % = 58.5 ; H % = 6.7 ; N % = 13.8 ;

Example 9 Preparation of 2,2-dimethyl-7-isopropoχy-

-6-methoxy-4-chromanone semicarbazone 2.64 g (10 mmoles) of 2,2-dimethyl-7-iso- propoxy-6-methoxy-4-chromanone are refluxed with 1.2 g of semicarbazide hydrochloride and 1.25 g of ammonium acetate In 25 ml of ethanol till the transformation of the most part of the starting substance (as detected by TLC), then the mixture is evaporated, the solid residue is washed with water and with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 158-160 ºC, which is useful for the next step without any purification. R_f = 0.12 (benzene/ethyl acetate 1:1)

0.49 (benzene/ethyl acetate/glacial acetic acid 7:3:1) 0.48 (chloroform/ethanol 9:1) Analysis: Calculated for C₁₆H₂₃N₃O₄ (molecular weight: 321)

C % = 59.86; H % = 7.22; N % = 13.09; Found: C % = 60.1 ; H % = 7.3 ; N % = 13.1 ;

Example 10

Preparation of 2,2-dimethyl-7-propargyloxy- -4-chromanone semicarbazone

9.2 g (40 mmoles) of 2,2-dimethyl-7-propargyl- oxy-4-chromanone are refluxed with 4.8 g of semicarbazide hydrochloride and 5 g of ammonium acetate in 100 ml of ethanol up to the transformation of the most part of the starting substance (as detected by TLC). Then, the mixture is evaporated, the solid residue is washed with water and with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 174-176 ºC which is useful for the next step without any purification. R_f = 0.12 (benzene/ethyl acetate 1:1)

0.54 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)

0.44 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₅H₁₇N₃O₃ (molecular weight: 287) C % = 62.77; H % = 5.97; N % = 14.64; Found: C % = 63.1 ; H % = 6.05; N % = 14.8 ;

Example 11

Preparation of 7-n-butoxy-2,2-dimethyl-4- -chromanone semicarbazone 9.92 g (40 mmoles) of 7-n-butoxy-2,2-dimethyl-

-4-chromanone are refluxed with 4.8 g of semicarbazide hydrochloride and 5 g of ammonium acetate in 80 ml of ethanol up to the transformation of the most part of the starting substances (as detected by TLC). Then, the mixture is evaporated, the solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 148-151 °C, which is useful for the next step or as intermediate for other reactions without any purification.

R_f = 0.14 (benzene/ethyl acetate = 1:1)

0.51 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.49 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₆H₂₃N₃O₃ (molecular weight: 305)

C % = 63 ; H % = 7.6 ; N % = 13.78; Found: C % = 63.2 ; H % = 1.6 ; N % = 13.9 ; E x a mp l e 12

Preparation of 2.2-dimethyl-7-n-propoxy-4- -chromanone semicarbazone

2.34 g (10 mmoles) of 2,2-dimethyl-7-n-propoxy- -4-chromanone are refluxed with 1.2 g of semicarbazide hydrochloride and 1.25 g of ammonium acetate In 25 ml of ethanol up to the transformation of the most part of the starting substance (as detected by TLC). Then, the mixture is evaporated, the solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 194-196 °C, which is useful for cyclization without any purification. R_f = 0.12 (benzene/ethyl acetate = 1:1) 0.52 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.45 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₅H₂₁N₃O₃ (molecular weight: 291) C % = 61.9 ; H % = 7.27; N % = 14.44;

Found: C % = 61.9 ; H % = 7.3 ; N % = 14.5 ;

Example 13

Preparation of 2 ,2-dimethyl-4-chromanone semicarbazone

1.76 g (10 mmoles) of 2,2-dimethyl-4-chromanone are refluxed with 1.2 g of semicarbazide hydrochloride and 1.25 g of ammonium acetate in 20 ml of ethanol up to the transformation of the most part of the starting substance (as detected by TLC). Then, the mixture is evaporated, the solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound m.p.: 193- 195 °C, which is useful for further transformations without any purification R_f = 0.19 (benzene/ethyl acetate = 1:1)

0.58 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.49 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₂H₁₅N₃O₂ (molecular weight: 233)

C % = 61.85; H % = 6.49; N % = 18.03; Found: C % = 61.6 ; H % = 6.6 ; N % = 18.2 ;

Example 14

Preparation of 4-chromanone semicarbazone 2.5 g (16.9 mmoles) of 4-chromanone are refluxed with 1.88 g (17 mmoles) of semicarbazide hydrochloride and 2.12 g of ammonium acetate in 42 ml of ethanol till the transformation of the most part of the starting substance (as detected by TLC). Then, the mixture is evaporated and the solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound in a yield of 86.7 %, m.p.: 205-208 ºC, which is useful for the cyclization without recrystallization or other purification. R_f = 0.08 (benzene/ethyl acetate = 1:1)

0.51 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)

0.37 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₀H₁₁N₃O₂ (molecular weight: 205) C % = 58.58; H % = 5.41; N % = 20.5 ; Found: C % = 58.4 ; H % = 5.32; N % = 20.7 ;

Example 15

Preparation of 7-allyloxy-2,2-dimethyl-4- -chromanone semicarbazone 18.56 g (80 mmoles) of 7-allyloxy-2,2-dimethyl-

-4-chromanone are refluxed with 9.6 g of semi- carbazide hydrochloride and 10 g of ammonium acetate in 200 ml of ethanol till the transformation of the most part of the starting substance (as detected by TLC). Then, the mixture is evaporated and the solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 173-175 ºC, which is chromatographically uniform and useful for cycllzations with any further purification. R_f = 0.08 (benzene/ethyl acetate = 1:1)

0.54 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.49 (chloroform/ethanol = 9:1) Analysis: Calculated for C₁₅H₁₉N₃O₃ (molecular weight: 289) C % = 62.27; H % = 6.62; N % = 14.52; Found: C % = 62.1 ; H % = 6.5 ; N % = 14.6 ;

Example 16 Preparation of 7-propargyloxy-2,2,5-trimethyl-

-4-chromanone semicarbazone

2.44 g (10 mmoles) of 7-propargyloxy-2,2,5-

-trimethyl-4-chromanone are refluxed with 1.2 g of semicarbazide hydrochloride and 1.2 g of ammonium acetate in 25 ml of ethanol till the transformation of the most part of the starting substance (as detected by TLC), thenthe mixture is evaporated. The solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 195-198 °C, which is useful for further transformations without any purification. R_f = 0.11 (benzene/ethyl acetate = 1:1)

0.51 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1) 0.44 (chloroform/ethanol = 9:1) Analysis :

Calculated for C₁₆H₁₉N₃O₃ (molecular weight: 301) C % = 63.84; H % = 6.36; N % = 13.96;

Found C% = 64.1 ; H%= 6.5 N% = 14.1 ;

Example 17

Preparation of 7-propargyloxy-2,2,8-trimethyl- -4-chromanone semicarbazone 9.77 g (40 mmoles) of 7-propargyloxy-2,2,8- -trimethyl-4-chromanone are refluxed with 4.8 g of semicarbazide hydrochloride and 5 g of ammonium acetate in 100 ml of ethanol till the transformation of the most part of the starting substance (as detected by TLC) and evaporated. The solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 193-196 °C, which is useful as intermediate for further reactions without any purification. R_f = 0.15 (benzene/ethyl acetate = 1:1) 0.56 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.46 (chloroform/ethanol = 9:1) Analysis:

Found: C % = 64 ; H % = 6.5 ; N % = 13.9 ;

Example 18

Preparation of 2,2-dirnethyl-6,7-ethylenedioxy-

-4-chromanone semicarbazone

2.34 g (10 mmoles) of 2,2-dimethyl-6,7-ethylene- dioxy-4-chromanone . are refluxed with 1.2 g of semicarbazide hydrochloride and 1.2 g of ammonium acetate in 20 ml of ethanol till the transformation of the most part of the starting substance (as detected by TLC), then evaporated. The solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate to give the title compound, m.p.: 203-206 ºC, which is useful for cyclization reactions without any purification. R_f = 0.12 (benzene/ethyl acetate = 1:1)

0.53 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)

0.44 (chloroform/ethanol = 1:1) Analysis: Calculated for C₁₄H₁₇N₃O₄ (molecular weight: 291

C % = 57.78; H % = 5.89; N % = 14.44 found: C % = 57.6 ; H % = 5.9 ; N % = 14.3

Example 19

Preparation of 2,2-dimethyl-6,7-methylenedioxy-

-4-chromanone semicarbazone

8.8 g (40 mmoles) of 2 ,2-dimethyl-6,7-methylene- dioxy-4-chromanone are refluxed with 4.8 g of semicarbazide hydrochloride and 5 g of ammonium acetate in 100 ml of ethanol till the transformation of the most part of the starting substance (as detected by

TLC), then evaporated. The solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 188-191 °C, which is useful for further reactions without any purification.

R_f = 0.08 (benzene/ethyl acetate = 1:1)

0.70 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.41 (chloroform/ethanol = 9:1)

Analysis:

Calculated for C₁₃H₁₅N₂O₄ (molecular weight: 277)

C % = 56.36; H % = 5.46; N % = 15.17; found: C % = 56.5 ; H % = 5.6 ; N % = 15.3 . Ex a mp le 20

Preparation of 2,2-dimethyl-7,8-ethylenedioxy- -4-chromanone semicarbazone

2.34 g (10 mmoles) of 2,2-dimethyl-7,8-ethylene dioxy-4-chromanon are refluxed with 1.2 g of semicarbazide hydrochloride and 1.25 g of ammonium acetate in 25 ml of isopropanol till the transformation of the most part of the starting substance (as detected by TLC), then evaporated. The solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 236-238 °C, which can be used without any purification.

R_f = 0.07 (benzene/ethyl acetate = 1:1) 0.50 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1) 0.43 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₄H₁₇N₃O₄ (molecular weight: 291) C % = 57.78; H % =.5.89; N % = 14.44; found: C % = 57.6 ; H % = 5.7 ; N % = 14.4 .

Example 21

Preparation of 2 ,2-dimethyl-7,8-methylenedioxy- -4-chromanone semicarbazone

2.2 g (10 mmoles) of 2,2-dimethyl-7,8-methylene- dioxy-4-chromanone are refluxed with 1 . 2 g o f semicarbazi de hydrochloride and 1 . 25 g o f ammonium acetate in 25 ml of ethanol till the transformation of the most part of the starting substance (as detected by TLC), then evaporated. The solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate an dried to give the title compound, m.p.: 194-197 ºC, which is chromatographically uniform and useful for further transformations without any purification. R_f = 0.07 (benzene/ethyl acetate = 1:1)

0.52 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.61 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₃H₁₅N₃O₄ (molecular weight: 277)

C % = 56.36; H % = 5.46; N % = 15.17; found: C % = 56.2 ; H % = 5.4 ; N % = 15.3 . IR (KBr): 3490, 3150, 3050, 2980, 1679, 1643, 1458, 1408, 1357, 1059 cm^-1.

MS (El, 70 eV): 277 (M⁺, 70 %), 219 (91 %), 189 (38 %),

161 (16 %), 77 (21 %), 36 (100 %). 1H-NMR (200 MHz, DMSO-d₆, δ PPm as related to DSS): 1.25 (s, 6H, gem. dimethyl); 2.8 (s, C-3 CH₂, 2H); 6.0 (s, 2H, -O-CH₂-O-); 6.5 (d,

1H, aromatic); 7.3 (2H, NH₂); 7.8 (d, 1H, aromatic); 9.3 (s, 1H, NH). 1³C-NMR (50.3 (MHz, DMSO-d₆, δ ppm): 26.3, 35.2, 76.2.

101.8, 115.7, 118 139, 149, 157.

Example 22

Preparation of 2-phenyl-4-chromanone semicarbazone

A solution of 60 g of sodium acetate and 11.4 g (0.1 mole) of semicarbazide hydrochloride in 150 ml of water is added to a solution of 22.4 g (0.1 mole) of 4-flavanone in 500 ml of ethanol, then the mixture is refluxed till the complete transformation of the starting substance and then evaporated. The residue is diluted with water, the product is filtered, washed with water and dried to give the title compound in a yield of 19.5 g + 5.1 g (i.e. in a total yield of 87.2 %) which may be recrystallized from ethanol, however, it Is useful for cyclization without purification, m.p.: 192-194 °C. Analysis:

Calculated for C₁₆H₁₅N₃O₂ (molecular weight: 281)

C % = 68.3 ; H % = 5.37; N % = 14.94; found: C % = 68.3 ; H % = 5.5 ; N % = 15.0 .

Example 23

Preparation of 2,2-dimethyl-6,7-dipropargyl- oxy-4-chromanone semicarbazone 11.36 g (40 mmoles) of 2,2-dimethyl-6,7-di- propargyloxy-4-chromanone are refluxed with 4.8 g of semicarbazide hydrochloride and 5 g of ammonium acetate in 100 ml of ethanol for 12 hours, then evaporated. The solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 190-193 °C. R_f = 0.16 (benzene/ethyl acetate = 1:1)

0.46 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.4 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₈H₁₉N₃O₄ (molecular weight: 341)

C % = 63.39; H % = 5.61; N % = 12.32; found: C % = 63 ; H % = 5.7 ; N % = 12.2 .

Example 24

Preparation of 2 ,2-dimethyl-6-ethoxy-7-methoxy- -4-chromanon semicarbazone 10 g (40 mmoles) of 2,2-dimethyl-6-ethoxy- -7-methoxy-4-chromanone are refluxed with 4.8 g of semicarbazide hydrochloride and 5 g of ammonium acetate in 100 ml of ethanol for 12 hours, then evaporated. The solid residue is washed with water and then with an 1:1 mixture of benzene and ethyl acetate and dried to give the title compound, m.p.: 185-188 °C. R_f = 0.12 (benzene/ethyl acetate = 1:1)

0.51 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.35 (chloroform/ethanol = 9:1) Ana lysi s : Calculated for C₁₅H₂₁N₃O₄ (molecular weight: 307) C % = 58.68; H % = 6.9 ; N % = 13.69; found: C % = 57 ; H % = 6.0 ; N % = 13.75.

Example 25

Preparation of 4-phenyl-4H-selenadiazolo- [5,4-c][1]benzopyran

14.06 g (0.05 mole) of 2-phenyl-4-chromanone semicarbazone (prepared as described in Example 22) is heated in the solution of 5.55 g (0.05 mole) of selenium dioxide in 50 ml of glacial acetic acid at 80 °C for 3 hours under stirring. Then, the mixture Is diluted with water, extracted with chloroform and the combined organic phase is dried and evaporated under vacuum. When necessary, the thus-obtained title product is recrystallized (e.g. from methanol, ethanol, petroleum ether or ethyl acetate), m.p.: 168-171 ºC. R_f = 0.22 (benzene/ethyl acetate = 1:1) 0.60 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.52 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₅H₁₀N₂OSe (molecular weight: 313) C % = 57.51; H % = 3.22; N % = 8.95 ; found: C % = 57.43; H % = 3.30; N % = 9.12 .

Example 26

Preparation of 4 ,4-dimethyl-7-methoxy-4H-selena- diazolo[5,4-c][1]benzopyran

5.1 g (20 mmoles) of 2,2-dimethyl-7-methoxy- -4-chromanone semicarbazone and 2.22 g (20 mmoles) of selenium dioxide are heated in 50 ml of glacial acetic acid under stirring until the gas evolution ceases, then evaporated. The residue is washed with water. On rubbing, the product solidifies, m.p.: 57- -60 °C. R_f = 0.68 (benzene/ethyl acetate = 1:1)

0.71 (benzene/ethyl acetate/glacial acetic acid = 7:3:1)

0.78 (chloroform/ethanol = 9:1) Analysis: Calculated for C₁₂H₁₂N₂O₂Se (molecular weight: 295)

C % = 48.85 H % = 4.10; N % 9.49 ; found : C % = 49.0 ; H % = 4.1 ; N % 9.6 .

Example 27 Preparation of 7 ,8-dimethoxy-

-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]benzo- pyran

5.87 g (20 mmoles) of 6,7-dimethoxy-2,2-di- methyl-4-chromanone semicarbazone and 2.5 g (22 mmoles) of selenium dioxide are heated in 50 ml of glacial acetic acid under stirring until the gas evolution ceases. The mixture is evaporated, the oily residue is dissolved in chloroform, washed with sodium hydrogen carbonate solution and then with water, dried, filtered through celite and then evaporated to give the title compound, m.p.: 98-100 °C. R_f = 0.62 (benzene/ethyl acetate = 1:1)

0.69 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)

0.86 (chloroform/ethanol = 9:1) Analysis: Calculated for C₁₃H₁₂N₂O₃Se (molecular weight: 325)

C % = 48.04; H % = 4.34; N % = 8.62 ; found: C % = 48.3 ; H % = 4.4 ; N % = 8.6 .

Example 28

Preparation of 4,4-dimethyl-7-ethoxy-8-methoxy- -4H-selenadiazolo[5,4-c][1]benzopyran 1.6 g (5 mmoles) of 2,2-dimethyl-6-methoxy-

-7-ethoxy-4-chromanone are heated in 12 ml of formic acid under stirring, whilst 0.6 g (about 5.4 mmoles) of selenium dioxide are added in several portions. After cessation of the gas evolution, the mixture is evaporated, the residue is dissolved in an 1:1 mixture of benzene and ethyl acetate and filtered through a silicagel layer. After evaporation, the residue solidifies (eventually rubbing is necessary), m.p.: 84-87 °C. R_f = 0.68 (benzene/ethyl acetate = 1:1)

0.68 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)

0.77 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₄H₁₆N₂O₃Se (molecular weight: 339) C % = 49.6 ; H % = 4.76; N % = 8.26 ; found: C % = 49.4 ; H % = 4.9 ; N % = 8.3 .

Example 29

Preparation of 6 ,7-dimethoxy-4,4-dimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran 2.93 g (10 mmoles) of 7,8-dimethoxy-2,2-di- methyl-4-chromanone semicarbazone are heated in 25 ml of propionic acid under stirring, whilst 1.33 g (12 mmoles) of selenium dioxide are portionwise added. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated and the product is recrystallized to give the title compound, m.p.: 225-227 °C. R_f = 0.66 (benzene/ethyl acetate = 1:1)

0.71 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)

0.77 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₃H₁₄N₂O₃Se (molecular weight: 325) C % =48.04; H % = 4.34; N % = 8.62 ; found: C % = 48.2 ; H % = 4.3 ; N % = 8.8 . E x amp le 30

Preparation of 7-methoxy-4.4,9-trimethy1- -4H-selenadiazolo[5,4-c][1]benzopyran To a heated solution of 27.7 g (100 mmoles) of 7-methoχy-2,2,5-trimethyl-4-chromanone semicarbazone in 250 ml of glacial acetic acid, 13.3 g (12 mmoles) of selenium dioxide are portionwise added under stirring and reacted until cessation of the gas evolution. The complet ion o f the cyclizat ion i s control led by TLC . The mixture is evaporated and the oily residue is crystallized by rubbing to give the title compound, m.p.: 90-93 °C. R_f = 0.72 (benzene/ethyl acetate = 1:1)

0.75 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)

0.75 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₃H₁₄N₂O₂Se (molecular weight: 309) C % = 50.53; H % = 4.57; N % = 9.07 ; found: C % = 50.7 ; H % = 4.5 ; N % = 9.2 .

Example 31

Preparation of 7-methoxy-4,4,6-trimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran 2.77 g (10 mmoles) of 7-methoxy-2,2,8-trimethyl-

-4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and control by TLC, the mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for the cyclization.) The oily residue is crystallized to give the title compound in a yield of 85.8 % , m.p.: 50-53 °C. R_f = 0.73 (benzene/ethyl acetate = 1:1) 0.77 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.77 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₃H₁₄N₂O₂Se (molecular weight: 309).

C % = 50.53; H % 4.57; N % = 9.07 ; found: C % = 50.3 ; H % 4.5 ; N % = 9.2 .

Example 32

Preparation of 7-propargyloxy- -4,4,9-trimathyI-4H-selenadiazolo[5,4-c][1]- benzopyran 3.01 g (10 mmoles) of 7-propargyloxy-2,2,5-

-trimethyl-4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used in the cyclization reaction). The oily residue is crystallized to give the title compound, m.p.: 63-65 ºC. R_f = 0.69 (benzene/ethyl acetate = 1:1) 0.72 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.76 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₅H₁₄N₂O₂Se (molecular weight: 333) C % = 54.1 ; H % = 4.24; N % = 8.41 ; found: C % = 54 ; H % = 4.4 ; N % = 8.3 .

Example 33

Preparation of 7 ,9-dimethoxy-4,4-dimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran

29.3 g (0.1 mole) of 5,7-dimethoxy-2,2-dimethyl- -4-chromanone semicarbazone dissolved in 250 ml of glacial acetic acid are reacted with 14.43 g of selenium dioxide added in several portions while heating and stirring. After cessation of the gas evolution, the mixture is filtered, evaporated and the residue is washed with water to give the title compound, m.p.: m.p. : 113-114 °C.

R_f = 0.67 (benzene/ethyl acetate = 1:1)

0.66 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1) 0.86 (chloroform/ethanol = 9:1) Analysis: Calculated for C₁₃H₁₄N₂O₃Se (molecular weight: 325)

C % = 48.04; H % = 4.34; N % = 8.62 ; found: C % = 48.0 ; H % = 4.3 ; N % = 8.7 .

Example 34

Preparation of 4,4-dimethyl-7,8-dipropargyl- oxy-4H-selenadiazolo[5,4-c][]benzopyran 3.41 g (10 mmoles) of 2,2-dimethyl-6,7-di- propargyloxy-4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 78-81 °C. R_f = 0.71 (benzene/ethyl acetate = 1:1)

0.71 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1)

0.74 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₇H₁₄N₂O₃Se (molecular weight: 373) C % = 54.74; H % = 3.78; N % = 7.51 ; found: C % = 54.4 ; H % = 4.0 ; N % = 7.4 .

Example 35

Preparation of 7-propargyloxy-4,4,6-trimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran 3.01 g (10 mmoles) of 7-propargyloxy-2,2,8-

-trimethyl-4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 113-115 ºC. R_f = 0.74 (benzene/ethyl acetate = 1:1)

0.74 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)

0.74 (chloroform/ethanol = 9:1) Analysis: Calculated for C₁₅H₁₄N₂O₂Se (molecular weight: 333)

C % = 54.1 ; H % = 4.24; N % = 8.41 ; found: C % = 54.21; H % = 4.04; N % = 8.5 .

Example 36

Preparation of 4,4-dimethyl-8-ethoxy-7-methoxy- -4H-selenadiazolo[5,4-c][1]benzopyran 3.07 g (10 mmoles) of 2,2-dimethyl-6-ethoxy- -7-methoxy-4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 70-72 °C. R_f = 0.69 (benzene/ethyl acetate = 1:1)

0.67 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1)

0.74 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₄H₁₆H₂O₃Se (molecular weight: 339) C % = 49.6 ; H % = 4.76; N % = 8.26; found: C % = 48.8 ; H % = 4.6 ; N % = 8.1 . E x amp le 37

Preparation of 4,4-dimethyl-selenadiazolo- [5,4-c]-dioxano[2,3-f]-4H-[1]benzopyran 2.91 g (10 mmoles) of 2,2-dimethyl-7,8-dioxano- -4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 127-131 °C. R_f = 0,6 (benzene/ethyl acetate = 1:1)

0,73 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)

0,55 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₃H₁₂N₂O₃Se (molecular weight: 323) C % = 48.34; H % = 3.75; N % = 8.67; found: C% = 48.0 H % = 4.1 ; N % = 8.7 .

Example 38

Preparation of 4 ,4-dimethylselenadiazolo- [5,4-c]-dioxolo[4,5-f]-4H-[1]benzopyran 2.77 g (10 mmoles) of 2,2-dimethyl-7,8-methy- lenedioxy-4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 151-154 °C . R_f = 0 . 64 ( benzene/ethy l aceta te = 1 : 1 )

0.7 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.73 (chloroform/ethanol = 9:1) Ana lysis :

Calculated for C₁₂H₁₀N₂O₃Se (molecular weight: 309)

C % = 46.64; H % = 3.26; N % = 9.07 ; found: C % = 46.4 ; H % = 3.0 ; N % = 9.1 .

Example 39

Preparation of 4 ,4-dimethylselenadiazolo- [5,4-c]-dioxano[2,3-e]-4H-[1]benzopyran 2.91 g (10 mmoles) of 2,2-dimethyl-6,7-dioxano- -4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 102-106 °C. R_f = 0.64 (benzene/ethyl acetate = 1:1)

0.76 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)

0.64 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₃H₁₂N₂O₃Se (molecular weight: 323) C % = 48.34; H % = 3.75; N % = 8.67 ; found: C % = 48.4 ; H % = 4.1 ; N % = 8.3 .

Example 40

Preparation of 4 ,4-dimethylselenadiazolo- [5,4-c]-dioxolo[4,5-e]-4H-[1]benzopyran 2.77 g (10 mmoles) of 2,2-dimethyl-6,7-methy- lenedioxy-4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 87-104 °C. R_f = 0.83 (benzene/ethyl acetate = 1:1)

0.75 (benzene/ethyl acetate/glacial acetic acid

= 7:3:1) 0.75 (chloroform/ethanol = 9:1) Analysis: Calculated for C₁₂H₁₀N_2O3Se (molecular weight: 309)

C % = 46.64; H % = 3.26; N % = 9.07 ; found: C % = 46.4 ; H % = 3.0 ; N % = 9.17 .

Example 41

Preparation of 6,7-dimethoxy-2,2-dimethyl- -4-chromanone acetylhydrazone 2.36 g (10 mmoles) of 6,7-dimethoxy-2,2-di- methyl-4-chromanone and 0.8 g (11 mmoles) of acetyl- hydrazine are refluxed in 25 ml of ethanol till the complete transformation. Then, the solvent is evaporated and the residue is recrystallized to give the title compound, m.p.: 98-102 °C.

R_f = 0.54 (benzene/ethyl acetate = 1:1)

0.52 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.48 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₅H₂₀N₂O₄ (molecular weight: 292)

C % = 61.64; H % = 6.85; N % = 9.59 ; found: C % = 61.4 : H % = 6.8 ; N % = 9.4 .

Example 42

Preparation of 7,9-dimethoxy-4,4-dimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran 33.6 g (0.1 mole) of 5,7-dimethoxy-2,2-dimethyl- -4-chromanone isopropyloxycarbonylhydrazone in 300 ml of glacial acetic acid are cyclized by portionwise adding 12.2 g (0.11 mole) of seleniumdioxide while mildly heating and stirring. The completion of the reaction is controlled by TLC. Then, the solvent is e.vaporated under vacuum and, if necessary, the residue is purified by recrystallization to give the title compound, m.p.: 113-114 ºC.

R_f = 0.67 (benzene/ethyl acetate = 1:1)

0.66 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.86 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₃H₁₄N₂O₃Se (molecular weight: 325)

C % = 48.04; H % = 4.34; N % = 8.62 ; found: C % = 48.0 ; H % = 4.4 ; N % = 8.7 .

Example 43

Preparation of 7 ,8-dimehoxy-4,4-dimethyI- -4H-selenadiazolo[5,4-c][1]benzopyran To 3.09 g (10 mmoles) of 6,7-dimethoxy-2,2- -dimethyl-4-chromanone thiosemicarbazone dissolved in 25 ml of tetrahydrofuran, 10 ml (13 mmoles) of selenous acid solution are dropwise added while stirring. The stirring is continued till the complete transformation (as detected by TLC). Then, the mixture is partially evaporated and water and chloroform are added to the residue. The organic phase is separated, washed with water, dried and evaporated to give the title compound, m.p.: 98-100 ºC.

R_f = 0.62 (benzene/ethyl acetate = 1:1)

0.69 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.86 (chloroform/ethanol = 9:1) Analysis: Calculated for C₁₃H₁₄N₂O₃Se (molecular weight: 325)

C % = 48.04; H % = 4.34; N % = 8.62 ; found: C % = 48.2 ; H % = 4.3 ; N % = 8.7 . Example 44

Preparation of 7-methoxy-4,4,9-trimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran 2.93 g (10 mmoles) of 7-methoxy-2,2,5-trimethyl- -2H-4-chromanone thiosemicarbazone are suspended in

15 ml of dioxane and cyclized by adding 1 ml (13 mmoles) of selenous acid under stirring. The end of the reaction is observed on the cessation of the gas evolution and by TLC control. The product is obtained by extraction or evaporation. In the most cases, the oily residue contains only the target compound and crystallizes readily to give the title compound, m.p.: 90 - 92.5 °C. R_f = 0.72 (benzene/ethyl acetate = 1:1)

0.75 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)

0.75 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₃H₁₄N₂O₂Se (molecular weight: 309) C % = 50.53; H % = 4.57; N % = 9.07 ; found C% 50.7 ; H % = 4.6 ; N % = 9.0 .

Example 45

Preparation of 4 , 4-dimethyl-7-ethoxy-4H- -selenadiazolo[5,4-c][1]benzopyran 1.44 g (13 mmoles) of selenium dioxide are portionwise added to the solution of 3.06 g (10 mmoles) of 2,2-dimethyl-7-ethoxy-4-chromanone N-ethoxycarbonyl- hydrazone in 25 ml of glacial acetic acid while heating and stirring. After completion of the reaction, the mixture is filtered and the solution is evaporated under vacuum for recovering the solvent. The oily residue becomes crystalline; it is uniform according to TLC and can directly be used in this form or as intermediate for further transformations without any purification, m.p 104-106 ºC. R_f = 0.75 (benzene/ethyl acetate = 1:1)

0.72 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.72 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₃H₁₄N₂O₂Se (molecular weight: 309)

C % = 50.53; H % = 4.57; N % = 9.07 ; found: C % = 50.4 ; H % = 4.5 ; N % = 9.2 .

Example 46

Preparation of 4-phenyl-4H-selenadiazolo- [5,4-c][1]benzopyran

1.33 g (12 mmoles) of selenium dioxide are portionwise added to the solution of 2.97 g (10 mmoles) of 2-phenyl-4-chromanone thiosemicarbazone in 25 ml of glacial acetic acid at 60 °C under stirring. The stirring is continued until the cessation of gas evolution and complete transformation of the starting material (as detected by TLC). Then, the mixture is evaporated and the recoved glacial acetic acid is used for the next cyclization. The residue is dissolved in chloroform, washed with alkali, dried and evaporated. If necessary, the residue is recrystallized to give the title compound, m.p.: 168-171 ºC. R_f = 0.22 (benzene/ethyl acetate = 1:1)

0.60 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.52 (chloroform/ethanol = 9:1) Analysis: Calculated for C₁₅H₁₀N₂OSe (molecular weight: 313) C % = 57.51; H % = 3.22; N % = 8.95 ; found: C % = 57.30; H % = 3.3 ; N % = 9.10 . Example 47

Preparation of 7-methoxy-4,4,6-trimethyl-4H- -selenadiazolo[5,4-c][1]benzopyran 2.92 g (10 mmoles) of 7-methoxy-2,2,8-trimethyl- -4-chromanone N-methoxycarbonylhydrazone in the mixture of 30 ml of dioxane and 10 ml of water are cyclized by adding 5 ml (11 mmoles) of selenous acid under stirring. The completion of the reaction is followed by TLC. Then, the reaction mixture is filtered, evaporated and recrystallized from benzene, if necessary, to give the title compound, m.p.: 58-60 ºC. The thus-obtained product can directly be used in this form or as intermediate.

R_f = 0.68 (benzene/ethyl acetate = 1:1) 0.71 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.78 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₃H₁₄N₂O₂Se (molecular weight: 309) C % = 48.85; H % = 4.10; N % = 9.49 ; found: C % = 49.0 ; H % = 4.2 ; N % = 9.6 .

Example 48

Preparation of 4,4-dimethyl-7-methoxy-4H- -selenadiazolo[5,4-c][1]benzopyran

2.78 g (10 mmoles) of 2,2-dimethyl-7-methoxy- -4-chromanone N-methoxycarbonylhydrazone are stirred with 1.33 g (12 mmoles) of selenium dioxide in 25 ml of glacial acetic acid under mildly stirring till the cessation of the gas evolution. The stirring is continued up to completion of the reaction (as detected by TLC), then filtered and evaporated to give the title compound, m.p.: 58-60 ºC, which can directly be used in this form or as intermediate R_f = 0.68 (benzene/ethyl acetate = 1:1)

0.71 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.78 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₂H₁₂N₂O₂Se (molecular weight: 295)

C % = 48.85; H % = 4.10; N % = 9.49 ; found: C % = 48.9 ; H % = 4.2 ; N % = 9.6 .

Example 49

Preparation of 7-allyloxy-4,4-dimethyl-4H- -selenadiazolo[5,4-c][1]benzopyran 11.52 g (40 mmoles) of 7-allyloxy-2,2-dimethyl- -4-chromanone acetylhydrazone in 100 ml of propionic acid are cyclized by portionwise adding 5.0 g (45 mmoles) of selenium dioxide. After cessation of the gas evolution and completion of the reaction (as detected by TLC), the mixture is evaporated, whereby 90 to 95 % of the propionic acid are recovered. The working-up may be carried out in such a way that the thus-obtained product is dissolved in ethyl acetate, the organic phase is washed with alkali, dried and evaporated to give the title compound in a yield of 88 % , m.p.: 63- -65 ºC after recrystallization from a mixture of benzene and ethyl acetate).

R_f = 0.69 (benzene/ethyl acetate = 1:1)

0.78 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.70 (chloroform/ethanol = 9:1) Analysis: Calculated for C₁₄H₁₄N₂O₂Se (molecular weight: 321)

C % = 52.33; H % = 4.36; N % = 8.72 ; found: C % = 52.2 ; H % = 4.2 ; N % = 8.8 . E xa mp le 50

Preparation of 4,4-dimethyl-7-proparqyloχy- -4H-selenadiazolo[5,4-c][1]benzopyran 39.8 g (0.1 mole) of 2,2-dimethyl-7-propargyl- oxy-2H-4-chromanone tosylhydrazone are suspended in 150 ml of dioxane and 10 ml of water and cyclized by adding 13.32 g (0.12 mole) of selenium dioxide while stirring. The completion of the reaction is controlled by TLC. Then, the reaction mixture is evaporated and the oily residue is crystallized to give the title compound, m.p.: 83-85 ºC. R_f = 0.7 (benzene/ethyl acetate = 1:1)

0.73 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1) 0.66 (chloroform/ethanol = 9:1) Analysis: Calculated for C₁₄H₁₂N₂O₂Se (molecular weight: 319)

C % = 52.71; H % = 3.79; N % = 8.78 ; found: C % = 52.4 ; H % = 3.7 ; N % = 8.9 .

Example 51

Preparation of 6,7-dimethoxy-4,4-dimethyl-4H- -selenadiazolo[5,4-c][1]benzopyran 2.5 g of 7,8-dimethoxy-2,2-dimethyl-4-chroma- none hydrazone are cyclized in 25 ml of tetrahydrofuran by portionwise adding 2.0 g (12 mmoles) of selenium oxychloride while stirring. After the complete transformation of the starting material (as detected by TLC), the reaction mixture is heated under stirring for one additional hour, then evaporated, if necessary, and the residue is recrystallized from a suitable solvent to give the title compound. R_f = 0.66 (benzene/ethyl acetate = 1:1)

0.71 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)

0.77 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₃H₁₄N₂O₃Se (molecular weight: 325)

C % = 48.04; H % = 4.34; N % = 8.62 ; found: C % = 48.2 ; H % = 4.3 ; N % = 8.7 .

Example 52

Preparation of 4,4-dimethyl-7-ethoxy-8- -methoxy-4H-selenadiazolo[5,4-c][1]benzopyran 34.2 g (0.1 mole) of 2,2-dimethyl-6-methoxy- -7-ethoxy-4-chromanone N-methanesulfonylhydrazone are cyclized in 350 ml of formic acid by portionwise adding 14.43 g (0.13 mole) of selenium dioxide while stirring. After TLC control, the reaction mixture Is diluted with water, neutralized and the product is separated by extraction into chloroform. After evaporation, the title product becomes crystalline, m.p.: 85-87 ºC, and can be used either directly in this form or as intermediate.

R_f = 0.68 (benzene/ethyl acetate = 1:1) 0.68 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.77 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₄H₁₆N₂O₃Se (molecular weight: 339) C % = 49.6 ; H % = 4.76; N % = 8.26 ; found C % = 49.4 ; H % = 4.8 N% = 8.4

Example 53

Preparation of 4,4-dimethyl-7,8-dipropargyl- oxy-4H-selenadiazolo[5,4-c][1]benzopyran 3.41 g (10 mmoles) of 2, 2-dimethyl-6,7-di- propargyloxy-4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 78-81 ºC. R_f = 0.71 (benzene/ethyl acetate = 1:1)

0.71 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.74 (chloroform/ethanol = 9:1) Analysis: Calculated for C₁₇H₁₄N₂O₃Se (molecular weight: 373) C % = 54.74; H % = 3.78; N % = 7.51 ; found: C % = 54.4 ; H % = 4.0 ; N % = 7.4 .

Example 54 Preparation of 4,4-dimethyl-8-ethoxy-7-methoxy-

-4H-selenadiazolo[5,4-c][1]benzopyran 3.07 g (10 mmoles) of 2,2-dimethyl-6-ethoxy- -7-methoxy-4--chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 70-72 °C. R_f = 0.69 (benzene/ethyl acetate = 1:1)

0.67 (benzene/ethyl acetate/glacial acetic acid = 0.74 = 7:3:1)

(chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₄H₁₆N₂O₃Se3 (molecular weight: 339)

C % = 49.6 ; H % = 4.76; N % = 8.26 ; found: C % = 48.8 ; H % = 4.6 ; N % = 8.1 . Example 55

Preparatin of 4,4-dimethylselenadiazolo- [5,4-c]-dioxolo[4,5-e]-4H-[1]benzopyran 2.77 g (10 mmoles) of 2,2-dimethyl-6,7-methyle- nedioxy-4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture Is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 87-104 ºC. R_f = 0.83 (benzene/ethyl acetate = 1:1)

0.75 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.75 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₂H₁₀N₂O₃Se (molecular weight: 309) C % = 46.64; H % = 3.26; N % = 9.07 ; found: C % = 46.4 H % = 3.0 N % = 9.17

Example 56

Preparation of 4 ,4-dimethylselenadiazolo- [5,4-c]-dioxolo[4,5-f]-4H-[1]benzopyran 2.77 g (10 mmoles) of 2,2-dimethyl-7,8-methyle- nedioxy-4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 151-154 °C. R_f = 0.64 (benzene/ethyl acetate = 1:1)

0.7 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.73 (chloroform/ethanol = 9:1) Analysis: Calculated for C ₁₂H₁₀N₂O₃Se (molecular weight: 309)

Example 57

Preparation of 4,4-dimethylselenadiazolo- [5,4-c]-dioxano[2,3-f]-4H-[1]benzopyran 2.91 g (10 mmoles) of 2,2-dimethyl-7,8-dioxano- -4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 127-131 ºC. R_f = 0.6 (benzene/ethyl acetate = 1:1)

0.73 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)

0.55 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₃H₁₂N₂O₃Se (molecular weight: 323) C% = 48.34; H % = 3.75; N % = 8.67; found: C % = 48.0 ; H % = 4.1 ; N % = 8.7 .

Example 58

Preparation of 4 ,4-dimethylselenadiazolo- [5,4-c]-dioxano[2,3-e]-4H-[1]benzopyran 2.91 g (10 mmoles) of 2,2-dimethyl-6,7-dioxano- -4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cycliza- tion.) The oily residue is crystallized to give the title compound, m.p.: 102-106 ºC.

R_F = 0.64 (benzene/ethyl acetate = 1:1)

0.76 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)

0.64 (chloroform/ethanol = 9:1) Analysis: Calculated for C₁₃H₁₂N₂O₃Se (molecular weight: 323)

C % = 48.34; H % = 3.75; N % = 8.67 ; found: C % = 48.4 ; H % = 4.1 ; N % = 8.3 .

Example 59

Preparation of 7-propargyloxy-4,4,9-trimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran 3.01 g (10 mmoles) of 7-propargyloxy-2,2,5-

-trimethyl-4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound, m.p.: 63-65 ºC. R_f - 0.69 (benzene/ethyl acetate = 1:1)

0.72 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.76 (chloroform/ethanol = 9:1) Analysis: Calculated for C₁₅H₁₄N₂O₂Se (molecular weight: 333)

C % = 54.1 ; H % = 4.24; N % = 8.41 ; found: C % = 54.0 ; H % = 4.4 ; N % = 8.3 .

Example 60

Preparation of 7-propargyloxy-4,4,6-trimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran 3.01 g (10 mmoles) of 7-propargyloxy-2,2,8- -trimethyl-4-chromanone semicarbazone in 20 ml of glacial acetic acid are oxidized by portionwise adding 1.33 g (12 mmoles) of selenium dioxide while heating and stirring. After cessation of the gas evolution and TLC control, the reaction mixture is evaporated. (The recovered glacial acetic acid may repeatedly be used for cyclization.) The oily residue is crystallized to give the title compound m. p 113-115

R_f = 0.74 (benzene/ethyl acetate = 1:1)

0.74 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.74 (chloroform/ethanol = 9:1) Analysis:

Calculated for C_{1 5}H₁₄N₂O₂Se (molecular weight: 333)

C % = 54.1 H % = 4.24; N % = 8.41 ; found C% = 54.21; H % = 4.04; N % = 8.5 .

Example 61

Preparation of 4-phenyl-4H-selenadiazolo- [5,4-c][1]benzopyran

A mixture containing 2.87 g (10 mmoles) of 2-phenyldihydrobenzopyran-3-selenone, 1.11 g (11 mmoles) of triethylamine, and 2.18 g (11 mmoles) of tosyl azide in 15 ml of acetonitrile is kept at 22 °C for one day, then evaporated and the residue is recrystallized to give the title compound in a yield of 94 % m.p.: 168- -171 °C. R_f = 0.22 (benzene/ethyl acetate = 1:1)

0.60 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.52 (chloroform/ethanol = 9:1) Analysis: Calculated for C₁₅H₁₀N₂OSe (molecular weight: 313)

C % = 57.51; H % = 3.22; N % = 8.95 ; found: C % = 57.43; H % = 3.30; N % = 9.12 . Example 62

Preparation of 4,4-dimethyl-7-methoxy-4H-selena diazolo[5,4-c][1]benzopyran A mixture containing 2.69 g (10 mmoles) of 2,2-dimethyl-7-methoxy-dihydrobenzopyran-3-selenone,

2.18 g (11 mmoles) of tosyl azide and 1.11 g of triethylamine in 15 ml of dioxane is stirred at 20 to 25 °C for 20 hours, then evaporated and the residue is recrystallized to give the title compound in a yield of 92 %, m.p.: 57-60 °C.

R_f = 0.68 (benzene/ethyl acetate = 1:1)

0.71 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.78 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₂H₁₂N₂O₂Se (molecular weight: 295)

C % = 48.85; H % = 4.10; N % = 9.49 ; found: C % = 49.0 ; H % = 4.1 ; N % = 9.6 .

Example 63

Preparation of 7,8-dimethoxy-4,4-dimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran A mixture containing 29.9 g (0.1 mole) of 6,7-dimethoxy-2,2-dimethyldihydrobenzopyran-3-selenone, 11.1 g (110 mmoles) of triethylamine and 21.8 g (110 mmoles) of tosyl azide in 150 ml of acetonitrile is kept at 22 ºC for 22 hours, then evaporated and the residue is recrystallized to give the title compound in a yield of 92 %, m.p.: 98-100 °C. R_f = 0.62 (benzene/ethyl acetate = 1:1)

0.69 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.86 (chloroform/ethanol = 9:1) Analysis: Calculated for C₁₃H₁₄N₂O₃Se (molecular weight: 325) C % = 48.04; H % = 4.34; N % = 8.62 ; found: C % = 48.3 ; H % = 4.4 ; N % = 8.6 . E xamp le 64

Preparation of 4,4-dimethyl-7-ethoxy-8-methoxy-

-4H-selenadiazolo[5,4-c][1]benzopyran A mixture containing 3.13 g (10 mmoles) of 2,2-dimethyl-7-ethoxy-6-methoxydihydrobenzopyran-3- -selenone, 1.11 g (11 mmoles) of triethylamine and 2.18 g (11 mmoles) of tosyl azide in 20 ml of acetonitrile is kept at 20 °C for 20 hours. The solvent is recovered by evaporation under vacuum and the residue is crystallized to give the title compound, m.p.: 84-87 °C. R_f = 0.68 (benzene/ethyl acetate = 1:1)

0.68 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1) 0.77 (chloroform/ethanol = 9:1) Analysis: Calculated for C₁₄H_{1 6}N₂O₃Se (molecular weight: 339)

C % = 49.6 ; H % = 4.76; N % = 8.26 ; found: C % = 49.4 ; H % = 4.9 ; N % = 8.3 .

Example 65

Preparation of 6,7-dimethoxy-4,4-dimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran 2.18 g (11 mmoles) of tosyl azide are added to the solution of 2.99 g (10 mmoles) of 7,8-dimethoxy- -2,2-dimethyldihydrobenzopyran-3-selenone and 1.11 g (11 mmoles) of N-methylmorpholine in 15 ml of tetrahydrofuran, the mixture is kept at 15 to 25 °C for one day, then the solvent is recovered by evaporation and the product is recrystallized to give the title compound, m.p.: 225-227 °C. R_f = 0.66 (benzene/ethyl acetate = 1:1)

0.71 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1) 0.77 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₃H_{1 4}N₂O₃Se (molecular weight: 325)

C % = 48.04; H % = 4.34; N % = 8.62 ; found: C % = 48.2 ; H % = 4.3 ; N % = 8.8 .

Example 66

Preparation of 7,9-dlmethoxy-4,4-dimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran A mixture of 2.99 mg (1 mmole) of 5,7-dimethoxy- -2,2-dimethyl-dihydrobenzopyran-3-selenone, 0.111 g of triethylamine and 218 mg of tosyl azide in 3.0 ml of acetonitrile is kept at 20 to 25 °C for one day, then diluted with water, the precipitate is filtered and recrystallized to give the title compound in a yield of 88 %, m.p.: 113-114 °C.

R_f = 0.67 (benzene/ethyl acetate = 1:1)

0.66 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.86 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₃H_{1 4}N₂O₃Se (molecular weight: 325)

Example 67

Preparation of 7-methoxy-4,4,6-trimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran A mixture of 2.83 g (10 mmoles) of 7-methoxy- -2,2,8-trimethyldihydrobenzopyran-3-selenone, 1.1 g of N-methylpiperidine and 2.18 g of tosyl azide in 15 ml of acetonitrile is kept at 20 to 25 °C for 20 hours, then the solvent is recovered by evaporation under vacuum and the residue is recrystallized to give the title compound in a yield of 89% m .p 50-53 R_f = 0.73 (benzene/ethyl acetate = 1:1)

0.77 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.77 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₃H₁₄N₂O₂Se (molecular weight: 309)

C % = 50.53; H % = 4.57; N % = 9.07 ; found: C % = 50.3 ; H % = 4.5 ; N % = 9.2 .

Example 68

Preparation of 7-methoxy-4,4,9-trimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran A solution of 2.83 g (10 mmoles) of 7-methoxy- -2,2,5-trimethyl-dihydrobenzopyran-3-selenone, 1.0 g of piperidine and 2.18 g of tosyl azide in 25 ml of ethanol is reacted at 25 °C for 24 hours, then the solvent is recovered by distillation under vacuum and the residue is recrystallized to give the title compound in a 96 % yield, m.p.: 90-93 °C. R = 0.72 (benzene/ethyl acetate = 1:1)

0.75 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.75 (chloroform/ethanol = 9:1) Analysis: Calculated for C₁₃H₁₄N₂O₂Se (molecular weight: 309) C % = 50.53; H % = 4.57; N % = 9.07 ; found: C % = 50.7 ; H % = 4.5 ; N % = 9.2 .

Example 69

Preparation of 7-proparqyloxy-4,4,9-trimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran 3.07 g (10 mmoles) of 7-propargyloxy-2,2,5- -trimethyldihydrobenzopyran-3-selenone are reacted with 2.18 g of tosyl azide and an equimolar amount of phenyllithium in 30 ml of ether at 20 °C. The reac tion is followed by TLC. After the completion of the reaction, the solvent is evaporated under vacuum, the residue is dissolved in chloroform, washed with acid and then with saturated sodium chloride solution, then dried and evaporated to give the title compound in a yield of 76 % , m.p.: 63-65º C.

R_f = 0.69 (benzene/ethyl acetate = 1:1)

0.72 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.76 (chloroform/ethanol = 9:1)

Analysis:

Calculated for C₁₅H₁₄N₂O₂Se (molecular weight: 333)

C % =.54.1 ; H % = 4.24; N % = 8.41 ; found: C % = 54.0 ; H % = 4.4 ; N % = 8.3 .

Example 70

Preparation of 4,4-dimethyl-7,8-dipropargyl- oxy-4H-selenadiazolo[5,4-c][1]benzopyran

3.47 g (10 mmoles) of 2,2-dimethyl-6,7-di- propargyloxydihydrobenzopyran-3-selenone are reacted with 0.95 g (11 mmoles) of piperidine and 2.18 g (11 mmoles) of tosyl azide in 25 ml of dichloromethane at 20 to 25 °C. The completion of the reaction is detected by TLC. Then, the solvent is evaporated and the residue. is recrystallized to give the title compound in a yield of 85 %, m.p.: 78-81 °C.

R_f = 0.71 (benzene/ethyl acetate = 1:1)

0.71 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.74 (chloroform/ethanol = 9:1)

Analysis:

Calculated for C₁₇H₁₄N₂O₃Se (molecular weight: 373)

C % = 54.74; H % = 3.78; N % = 7.51 ; found: C % = 54.4 ; H % = 4.0 ; N % = 7.4 . E x amp le 71

Preparation of 4,4-dimethyl-8-ethoxy-7-methoxy- -4H-selenadiazolo[5,4-c][1]benzopyran A mixture containing 3.13 g (10 mmoles) of 2,2-dimethyl-6-ethoxy-7-methoxydihydrobenzopyran-3-

-selenone, 0.65 g (11 mmoles) of trimethylamine, 2.18 g (11 mmoles) of tosyl azide and 30 ml of acetonitrile is reacted at 20 to 25 °C for 20 hours. Then, the solvent is recovered by evaporation under vacuum and the residue is recrystallized to give the title compound in a yield of 88 %, m.p.: 70-72 °C. R_f = 0.69 (benzene/ethyl acetate = 1:1)

0.67 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1) 0.74 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₄H₁₆N₂O₃Se (molecular weight: 339) C % = 49.6 ; H % = 4.76; N % = 8.26 ; found: C % = 48.8 ; H % = 4.6 ; N % = 8.1 .

Example 72

Preparation of 4,4-dimethylselenadiazolo- [5,4-c]-dioxolo[4,5-f]-4H-[1]benzopyran A mixture of 2.83 g (10 mmoles) of 2,2-di- methyl-7,8-methylenedioxydihydrobenzopyran-3-selenone, 0.81 g (11 mmoles) of diethylamine, 2.18 g (11 mmoles) of tosyl azide and 20 ml of ethanol is reacted. The reaction is followed by TLC. After completion of the reaction, the solvent is recovered by evaporation and the residue is recrystallized to give the title compound in a yield of 94 %, m.p.: 151-154 °C. R_f = 0.64 (benzene/ethyl acetate = 1:1)

0.7 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1) 0.73 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₂H₁₀N₂O₃Se (molecular weight: 309)

Example 73

Preparation of 4,4-dimethylselenadiazolo- [5,4-c]-dioxano[2,3-e]-4H-[1]benzopyran A mixture of 2.97 g (10 mmoles) of 2,2-dlmethyl- -6,7-dioxanodihydrobenzopyran-3-selenone, 25 ml of diethylamine and 2.18 g (11 mmoles) of tosyl azide is reacted. The reaction is followed by TLC. After completion of the reaction, the solvent is evaporated (and again used). The residue is recrystallized to give the title compound in a yield of 92 %, m.p.: 102- -106 °C. R_f = 0.64 (benzene/ethyl acetate = 1:1)

0 .76(benzene/ethyl acetate/glacial acetic acid_.= = 7:3:1) 0.64 (chloroform/ethanol = 9:1) Analysis: Calculated for C₁₃ H₁₂N₂O₃Se (molecular weight: 323)

C % = 48.34; H % = 3.75; N % = 8.67 ; found: C % = 48.4 : H % = 4.1 ; N % = 8.5 .

Example 74

Preparation of 4,4-dimethylselenadiazolo- [5,4-c]-dioxolo[4,5-e]-4H-[1]benzopyran A mixture of 2.83 g (10 mmoles) of 2,2-dimethyl- -6,7-methylenedioxydihydrobenzopyran-3-selenone, 0.94 g (11 mmoles) of piperidine, 2.18 g of tosyl azide and 20 ml of acetonitrile is reacted at 20 to 25 °C for 20 hours. After completion of the reaction, the solvent is evaporated and again employed. The residue is recrystallized to give the title compound in a yield of 96 %, m.o.: 97-104 °C. R_f = 0.83 (benzene/ethyl acetate = 1:1)

0.75 (benzene/ethyl acetate/glacial acetic acid

= 7:3:1) 0.75 (chloroform/ethanol = 9:1) Analysis: Calculated for C₁₂H₁₀N₂O₃Se (molecular weight: 309)

Example 75

Preparation of 4,4-dimethylselenadiazolo- [5,4-c]-dioxano[2,3-f]-4H-[1]benzopyran A mixture containing 2.97 g (10 mmoles) of 2,2-dimethyl-6,7-dioxanodihydrobenzopyran-3-selenone, 1.11 g (11 mmoles) of triethylamine, 2.18 g (11 mmoles) of tosyl azide and 20 ml of acetonitrile is reacted at 20 °C for 20 hours. Then, the solvent is recovered by evaporation under vacuum and the product is recrystallized to give the title compound in a yield of 82 %, m.p.: 127-131 °C.

R_f = 0.6 (benzene/ethyl acetate = 1:1)

0.73 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.55 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₃H₁₂N₂O₃Se (molecular weight: 323) C % = 48.34; H % = 3.75; N % = 8.67 ; found: C% = 48.0 H % = 4.1 N % = 8.7

Example 76

Preparation of 7-propargyloxy-4,4,6-trimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran A mixture containing 3.07 g (10 mmoles) of 7-propargyloxy-2,2,8-trimethyldihydrobenzopyran-3-sele- none, 1.11 g (11 mmoles) of triethylamine, 2.18 g (11 mmoles) of tosyl azide and 25 ml of metanol is reacted at 20 to 25 °C for 24 hours. Then, the solvent is recovered by evaporation under vacuum and the product is recrystallized to give the title compound in a yield of 91 %, m.p.: 113-115 °C. R_f = 0.74 (benzene/ethyl acetate = 1:1)

0.74 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.74 (chloroform/ethanol = 9:1) Analysis: Calculated for C₁₅H₁₄N₂O₂Se (molecular weight: 333) C % = 54.1 ; H % = 4.24; N % = 8.41 ; found: C % = 54.21; H % = 4.04; N % = 8.5 .

Example 77 Preparation of 4-phenyl-4H-selenadiazolo- [5,4-c][1]benzothiopyran

2.18 g (11 mmoles) of tosyl azide are added to a mixture of 3.03 g (10 mmoles) of 2-phenyldihydro- benzothiopyran-3-selenone, 1.11 g (11 mmoles) of triethyl- amine and 30 ml of dichloromethane, then the mixture is let stand for 20 hours. The solvent is recovered by evaporation and the residue is recrystallized to give the title compound in a yield of 82 %, m.p.: 55- -58 °C. R = 0.73 (benzene/ethyl acetate = 1:1)

0.78 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.79 (chloroform/ethanol = 9:1) Analysis: Calculated for C₁₅H₁₀N₉SeS (molecular weight: 329)

C % = 54.765 H % = 3.06; N % = 8.52 ; found: C % = 55.1 ; H % = 3.13; N % = 8.38 . E x amp l e 78

Preparation of 7,8-dimethoxy-4,4-dimethyl- thiadiazolo[5,4-c][1]benzopyran A mixture containing 2.52 g (10 mmoles) of 6,7-dimethoxy-2,2-dimethyl-3,4-dihydro-2H-benzopyran- -3-thione, 0.96 g (11 mmoles) of morpholine, 2.18 g (11 mmoles) of tosyl azide and 25 ml of ethanol is reacted at 20 to 25 °C for 24 hours. The solvent is recovered by evaporation and the residue is recrystallized to give the title compound in a yield of 79 % , m.p.: 118-120 °C. R_f = 0.62 (benzene/ethyl acetate = 1:1)

0.59 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1) 0.86 (chloroform/ethanol = 9:1) Analysis: Calculated for C₁₃H₁₄N₂O₃Se (molecular weight: 278)

C % = 56.16; H % = 5.07; N % = 10.08; found: C % = 56.4 ; H % = 5.0 ; N % = 10.20.

Example 79

Preparation of 6,7-dimethoxy-2,2-dimethyl- -3,4-dihydro-2H-benzopyran-3-thione 2.36 g (10 mmoles) of 6,7-dimethoxy-2,2- -dimethyl-3,4-dihydro-2H-benzopyran-3-on and 4.44 g (20 mmoles) of phosphorus pentasulfide are refluxed in 50 ml of pyridine for 3 hours, and after completion of the reaction, the mixture is poured into 250 ml of ice-water. The precipitate is thoroughly triturated, filtered and dried to give the title compound in a yield of 88 %.

IR: 2960, 1620, 1520, 1260, 865 cm^-1 1H-NMR (

ppm, DMSO-d₆): 1.8 (6H), 3.6 (6H), 4.2 (2H),

7.2 (1H), 7.4 (1H) Analysis

Calculated for C₁₃H₁₆O₃S (molecular weight: 252)

C % = 61.96; H % = 6.4 ; S % = 12.7 ; found: C % = 62.0 ; H % = 6.51; S % = 11.68.

Example 80

Preparation of 6,7-dimethoxy-2,2-dimethyl- -3,4-dihydro-2H-benzopyran-3-selenone 2.36 g (10 mmoles) of 6,7-dimethoxy-2,2-di- methyl-3,4-dihydro-2H-benzopyran-3-one are refluxed with 9.2 g (20 mmoles) of phosphorous pentaselenide in 50 ml of pyridine for 3 hours, then poured in 200 ml of ice-cold 1:1 hydrochloric acid, and the product separated is extracted into chloroform, or benzene. The combined organic phase Is dried over anhydrous calcium chloride and evaporated to give the title compound in a yield of 92 %, which is pure enough for the next step.

IR: 2960, 1615, 1530, 1100, 870 cm^-1 1H-NMR (

ppm, DMSO-d₆): 2.0 (6H), 3.6 (6H), 4.2 (2H), 7.3 (1H), 7.5 (1H) Analysis:

Calculated for C₁₃H₁₆O₃Se (molecular weight: 299) C % = 52.22; H % = 5.39; found: C % = 53.0 ; H % = 5.46;

Example 81 Preparation of 4,4-dimethyl-7-methoxy-4H- selenadiazolo[5,4-c][1]benzopyran A solution of 2.81 g (10 mmoles) of 3-hydroxy- -1-(2'-hydroxy-4-methoxyphenyl)-3-methylbutanon-1-one semicarbazone in 25 ml of glacial acetic acid is boiled for one hour, then 1.11 g (10 mmoles) of selenium dioxide are portionwise added under continuous heating and stirring. The stirring and heating are continued until the gas evolution ceases and the starting substance disappears (as detected by TLC). Then, the acetic acid is evaporated under vacuum and the residue is recrystallized from ethanol or from a hydrocarbon to give the title compound, m.p.: 57-60 °C. R_f = 0.68 (benzene/ethyl acetate = 1:1)

0.71 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1)

N % = 9.49; found: N % = 9.6 .

The following compunds were prepared by using method described in Example 81:

4-Phenyl-4H-selenadiazolo[5,4-c][1]benzopyran, m.p.: 168-171 °C;

4,4-dimethyl-7-ethoxy-8-methoxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, m.p.:84-87 ºC;

6,7-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 125 - 127 °C;

7,9-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]ben- zopyran, m.p.: 113-114 °C;

7-methoxy-4,4,6-trimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 50-53 °C;

7-methoxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 90-93 °C;

7-propargyloxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran, m.p.: 63-65 °C;

4,4-dimethyl-7,8-dipropargyloxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, m.p.: 78-81 °C; and 4,4-dimethyl-8-ethoxy-7-methoxy-4H-selenadiazolo[5,4-c][1] be nzop yr an , m . p . : 70 -72 °C. 4,4-dimethyl-7,8-dimethoxy-4H-selenadiazolo[5,4-c[1]benzopyran, m.p. 98-100ºC Example 82

Preparation of 4,4-dimethylselenadiazolo- [5,4-c]-dioxolo[4,5-f]-4H-[1]benzopyran A solution containing 3.27 g (10 mmoles) of 5-(1'-hydroxy-1'-methyl)ethyl-4-(2-hydroxy-3,4- -methylenedioxy)phenyl-1,2,3-selenadiazole in 30 ml of glacial acetic acid is boiled for one hour, then set aside overnight. Then, the acetic acid is recovered by distillation (under atmospheric or reduced pressure) and the residue is recrystallized or dissolved in a water-immiscible solvent (e.g. chloroform) and washed with water to give the title compound, m.p.: 151-154 °C. R_f = 0.64 (benzene/ethyl acetate = 1:1)

0.70 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.73 (chloroform/ethanol = 9:1) Analysis: Calculated for C₁₂H₁₀N₂O₃Se (molecular weight: 309)

C % = 46.64; H % = 3.26; N % = 9.07; found: C % = 46.4; H % = 3.0; N % = 9.1.

The following compounds were prepared by using the process described in Example 82: 7,8-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 98-100 °C;

4,4-dimethylselenadiazolo[5,4-c]-dioxano[2,3-e]-4H-[1]- benzopyran, m.p.: 102-106 °C;

4,4-dimethylselenadiazolo[5,4-c]-dioxolo[4,5-e]-4H-[1]- benzopyran, m.p.: 87-104 °C;

4,4-dimethylselenadiazolo[5,4-c]-dioxano[2,3-f]-4H-[1]- benzopyran, m.p.: 127-131 °C;

7-propargyloxy-4,4,6-trimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 113-115 °C; 4,4-dimethyl-8-ethoxy-7-methoxy-4H-selenadiazolo[5,4-c]-[1]-benzopyran, m.p.: 70-72 °C; 4,4 -dimethyl-7-ethoxy-8-methoxy-4H-selenadiazolo[5,4-c]-[1]benzopyran, m.p. : 84-87 °C;

4,4-dimethyl-7-methoxy-4H-selenadiazolo[5,4-c][1]benzo- pyran, m.p. : 57-60 °C;

6,7-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p. : 125-127 °C; and

7-propargyloxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c][1] benzopyran, m.p. : 63-65 °C.

Example 83

Preparation of 4-phenyl-4H-selenadiazoIo- [5,4-c][1]benzothiopyran A mixture containing 3.90 g (10 mmoles) of

N-nitroso-N-(thiaflavanon-3-selenon-4-yl)urea, 50 ml of tetrahydrofuran and 10 ml of 10 % potassium hydroxide solution is stirred at 25 °C for 2 hours, then the solvent is evaporated under vacuum and the residue is purified by chromatography on a Kieselgel column to give the title compound, m.p.: 55-58 °C. R_f = 0.73 (benzene/ethyl acetate = 1:1)

0,78 (benzene/ethyl acetate/glacial acetic acid = = 7:3:1) 0.79 (chloroform/ethanol = 9:1) Analysis: Calculated for C₁₅H₁₀N₂SSe (molecular weight: 329)

N % = 8.52 ; found: N % = 8.38 .

The following compounds were prepared by using the process described in Example 83: 4-Phenyl-4H-selenadiazolo[5,4-c][1]benzopyran, m.p.: 168-171; 4,4-dimetnyl-7-methoxy-4H-selenadiazolo[5,4-c][1]benzo- pyran, m.p.: 57-60 ºC.

7,8-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 98-100 °C;

4,4-dimethyl-7-ethoxy-8-methoxy-4H-seIenadiazolo[5,4-c]- [1]benzopyran, m.p.: 84-87 °C.

6, 7-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 125-127 °C;

7,9-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 113-114 °C; 7-methoxy-4,4,6-trimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 50-53 °C; 7-methoxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 90-93 °C;

7-propargyloxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran, m.p. : 63-65 °C; 4,4-dimethyl-7,8-dipropargyloxi-4H-selenadiazolo[5,4-c]- [1]benzopyran, m.p.: 78-81 °C;

4,4-dimethyl-8-ethoxy-7-methoxy-4H-selenadiazolo[5,4-c]- [1[benzopyran, m.p.: 70-72 °C;

4,4-dimethylselenadiazolo[5,4-c]-dioxolo[4,5-f]-4H- -[1]benzopyran, m.p.: 151-154 °C;

4,4-dimethylselenadiazolo[5,4-c]-diσxano[2,3-e]-4H-

-[1]benzopyran, m.p.: 102-106 °C;

7-ρropargyloxy-4,4,6-trimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran, m.p.: 113-115 °C; and 7,8-dimethoxy-4,4-dimethyl-4H-thiadiazolo[5,4-c][1]benzo- pyran, m.p.: 118-120 °C.

Example 84

Preparation of 7,8-dimethoxy-4,4-dimethyl- -4H-selenadiazolo[5,4-c][1]benzopyran A mixture containing 3.11 g (10 mmoles) of 7,8-dimethoxy-4H-selenadiazolo[5,4-c][1]benzopyran- -4-one in 50 ml of anhydrous ether is added to the solution of 20 mmoles of methyl magnesium iodide in 20 ml of ether, then the mixture is refluxed for 2 hours under stirring and then evaporated. To the residue 25 ml of glacial acetic acid are added, the mixture is refluxed for one hour and then mixed with water and extracted with chloroform. The organic phase is washed with sodium carbonate solution, dried and evaporated to give the title compound in a yield of 85 %, m.p.: 98-100 °C. R_f = 0.62 (benzene/ethyl acetate = 1:1)

0.69 (benzene/ethyl acetate/glacial acetic acid =

= 7:3:1) 0.86 (chloroform/ethanol = 9:1) Analysis:

Calculated for C₁₃H₁₄N₂O₃Se (molecular weight: 325)

C % = 48.04; H % = 4.34; N% = 8.62 found: C % = 48.3 ; H% = 4.4 : N % = 8.6

The following compounds were prepared by using the process described in Example 84: 4,4-dimethyl-7,8-dipropargyloxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, m.p.: 78-81 °C; 4,4-dimethyl-8-ethoxy-7-methoxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, m.p.: 70-72 °C; 7,8-diethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: < 50 °C;

7-allyloxy-4,4-dImethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 63-65 °C;

7,8-dimethoxy-4,4-dimethyl-4H-thiadiazolo[5,4-c7[1]benzo- pyran, m.p.: 118-120 °C;

7-propargyloxy-4,4,6-trimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran, m.p.: 113-115 °C; 7-propargyloxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran, m.p.: 63-65 °C;

4,4-dimethyl-7-propargyloxy-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 83-85 °C;

4,4-dimethyl-7-ethoxy-8-methoxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, m.p.: 84-87 °C;

4,4-dimethyl-7-ethoxy-4H-selenadiazolo[5,4-c7[1]benzo- pyran, m.p.: 104-106 °C;

7,9-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c7[1]- benzopyran, m.p.: 113-114 °C; 7-methoxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, m.p.: 90-93 °C;

6,7-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]-benzopyran, m.p.: 30-32 °C; and

7-methoxy-4,4,6-trimethyl-4H-selenadiazolo[5,4-c][1]-benzopyran, m.p.: 50-53 °C. Biological action

The effects of the compounds of the invention were studied by using the following biological tes t systems: 1) the in vivo insecticide and allatocide action on freshly shedded L4-stage locust (Locusta migratoria) nymphs;

2) the in vitro allatocide action on the corpora allata taken from freshly shedded L5-stage locust nymphs by using the method of Shoeneveld (1982);

3) the nematocide action on synchronized Ll-stage larvae of Caenorhabditis elegans Cb 678 strain;

4) the insecticide action on the large white butterfly (Pieris brassicae), fall webworm (Hyphantria cunea), potato beetle (Leptinotarsa decemlineata) and pea green-fly aphis (Acyrthosiphon pisum);

5) in other bactericidal, fungicidal and insecticidal including acaricidal tests.

1) In vivo tests on locusts

The locusts were bred and kept according to the international standards, in rooms thermostated at 29 °C under a stable moisture content, with a day- -part change of the temperature. The L4 nymphs of the locust (Locusta migratoria) freshly shedded within

24 hours were topically treated with the test compounds dissolved in acetone. The animals were anaesthetized by carbon dioxide. The control animals were treated only with acetone. The locusts were daily observed for 21 days and the time and number of the perishments and sheddings were registered. After 21 days, the presence of the eventual adultoids were also investigated.

The effects of the compounds tested were as follows: 4,4-dimethyl-7-methoxy-4H-selenadiazolo[5,4-c][1]benzopyran:

On using a dose of 50 μg/ anima l , one ou t o f 40 animals on ly surv ived , whereas the perishment was total by using a higher dose.

4,4-dimethyl-7-ethoxy-8-methoxy-4H-selenadiazolo[5,4-c]- [1]benzopyran:

The LC₅₀ value of this compound is at a dose of 25 to 50 μg/animal. Survival was observed even at a dose of 100 μg/animal.

6,7-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran: Nearly no survival was observed at a dose of 50 μg/animal.

7-Methoxy-4,4,6-trimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran: The lethality is 95 to 100 % by using a dose of 400 or 100 μg/animal.

2) In vitro CA test

These investigations were carried out by using Schoeneveld's in vitro test (1982). Most of the test compounds were used at four dose levels (5, 10, 50 or 100 μg/ml of medium). The surviving glands were not stained by using a vital dye (acridine orange) after 24 hours, whereas the perished organs showed a staining.

The results of the in vitro CA test determined by using the above method are summarized in Table 1.

Notes to Table 1:

* These values are expressed as μg of selenium. + It is important that no allatocide effect is observed in vitro up to 100 μg.

0: No effect Not determined

The chemical names of the numbered compounds in Table 1 are as follows:

1: 4,4-dimethyl-7-methoxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, 2: 7,8-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran, 3: 4-phenyl-4H-selenadiazolo[5,4-c][1]benzopyran,

4: 7-methoxy-4,4,6-trirnethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran, 5: 6,7-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran,

6: 7-methoxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran, 7: 7,9-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran, 8: 4,4-dlmethyl-7-ethoxy-8-methoxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, 9: 4,4-dimethyl-7-propargyloxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, 10: 7-propargyloxy-4,4,6-trimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran,

11: 4,4-dimethyl-4H-[1,4]-dioxano[2,3-g]selenadiazolo- [5,4-c][1]benzopyran, 12. 4,4-dimethyl-4H-[1,4[-dioxano[2,3-h[selenadiazolo- [5,4-c][1]benzopyran, 13: 4,4-dimethyl-4H-[1,3[-dioxolo[4,5-g]selenadiazolo- [5,4-c][1]benzopyran and 14: selenium dioxide.

3) Study of the nematocide effect Synchronized L1-stage larvae obtained by the hypochlorite method from Caenorhabditis elegans (C. elegans, laboratory threadworm) CB 678 strain were put onto NGM agar chilled in the holes of a microtitrator sheet (Brenner, 1974) also containing the test substance in the appropriate concentrations. Usually, a dilution in the dose interval between 0 and 1000, or between 0 and 500 μg/ml, respectively was used. A part of the compounds was subjected to a preceeding experiment with concentrations of 5, 50, 500 and 5000 μg/ml. Four repetitions were carried out for each concentration with 15 to 20 animals for each repetition. The sheets also contained E. coli OP 50 bacterial nutriment. After 48 hours, the number of the living, normally developed animals was determined. The percentage ratio of this number related to the control represents the percentage of the survival. In the majority of the cases, this ratio was useful for the approximately accurate calculation of the LD₅₀ and LD₉₅ values.

The results of the nematocide test are summarized in Table 2. The numbering of the compounds in Table 2 is the same as shown in Table 1. Further substances are as follows: 15: 4,4-dimethyl-7-ethoxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, 16: KSeCN, 17: 7-allyloxy-4,4-dimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran, and 18: 4,4-dimethyl-4H-[1,3]-dioxolo[4,5-h]selenadiazolo- [5,4-c][1]benzopyran.

/ /

Claims

What we claim is

1. Compounds of the general formula (I)

(I)

wherein R¹ and R² are independently from each other hydrogen, an unsubstituted or optionally suitably substituted alkyl or aryl group; or

R¹ and R² together may be a cycloalkyl group; R³ is hydrogen; an optionally protected hydroxyl group; an alkyl, alkoxy, O-trialkyltin group; a phosphoric acid, thiophosphoric acid or phosphorous acid alkyl or aryl ester group connected through the oxygen atom; an acyloxy, acyloxyalkoxy, O-trialkylsilyl, aryloxy, alkenyloxy, alkynyloxy, cycloalkyloxy, cyclo- alkenyloxy, cycloalkylalkoxy group; an acyloxy or alkoxy group substituted by phosphoric acid, phosphonic acid or their esters; or two adjacent R³ groups together may represent: an -O-(CH₂)_m-O-group, wherein m is 1, 2, 3 or 4; or a condensed aromatic ring; or an -O-(CH₂)_m-(O)_z- group, wherein m is as defined above and z is 0 or 1; or an -O-P(Cl)-O-, -O-P(OC₂H₅)-O-, -O-P=O(OC₂H₅)-O-, -O-P=S(OC₂H₅)-O-, -O-(C=O)-O-, -O-(C=S)-O-, -O-P=O(SC₂H₅)-O-, -O-P=S(SC₂H₅)-O- or an -O-(S=O)-O- group; or a halogen or a haloalkyl, nitro, amino or suitably substituted amino group; an alkoxy group substituted by an alkylamino or a dialkylamino group; or a nitrile, mercapto, optionally substituted alkylthio group; an optionally ring-substituted aralkyloxy group; an acyl group; or two adjacent R³ groups together may also represent a -C=C-C(=O)-O- and -C=C-C=(CH₃)₂-O- group; is 0, 1, 2, 3 or 4, and these R³ groups may have, independently from each other, any meaning defined for the R³ groups, Q¹ is oxygen, sulfur, SO or SO₂; Q² is sulfur or selenium as well as their salts having valuable biological effects

2. A compound as claimed in claim 1, wherein R¹ and R² are each a methyl group.

3. A compound as claimed in claim 1 wherein

R³ is a methoxy group.

4. A compound as claimed in claim 1 wherein R³ is a methoxy group and n is 2.

5. A compound as claimed in claim 1, wherein

R¹ and R² are each a methyl group and R³ means a methoxy group.

6. A compound selected from the group consisting of 4-phenyl-4H-selenadiazolo[5,4-c][1]benzopyran, 4,4-dimethyl-7-methoxy-4H-selenadiazolo[5,4-c][1]benzo¬pyran, 7,8-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c]-[1]benzopyran, 4,4-dimethyl-8-ethoxy-7-methoxy-4H-selenadiazolo[5,4-c]- [1]beneopyran, 4,4-dimethyl-7-ethoxy-8-methoxy-4H-selenadiazolo[5,4-c]-[1]benzopyran, 6,7-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c]-[1]benzopyran, 7,9-dimethoxy-4,4-dimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran,

7-methoxy-4,4,6-trimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, 7-methoxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c][1]- benzopyran, 7-propargyloxy-4,4,9-trimethyl-4H-selenadiazolo[5,4-c] [1]benzopyran, 4,4-dimethyl-7,8-dipropargyloxy-4H-selenadiazolo[5,4-c]- [1]benzopyran, 4,4-dimethylselenadiazolo[5,4-c]-dioxolo[4,5-f]-4H- -[1]benzopyran,

4,4-dimethylselenadiazolo[5,4-c]-dioxano[2,3-e]-4H- -[1]benzopyran, 4,4-dimethylselenadiazolo[5,4-c]-dioxolo[4,5-e]-4H- -[1]benzopyran,

4,4-dimethylsεlenadiazolo[5,4-c]-dioxano[2,3-f]-4H- -[1]benzopyran,

7-propargyloxy-4,4,6-trimethyl-4H-selenadiazolo[5,4-c]- [1]benzopyran,

4-phenyl-4H-selenadiazolo[5,4-c][1]benzothiopyran, 7,8-dimethoxy-4,4-dimethyl-4H-thiadiazolo[5,4-c][1]- benzopyran and the salts of these compounds. 7. A fungicide, nematocide, acaricide, bactericide and insecticide composition which comprises as active ingredient a 4H-selenadiazolo[5,4-c][1]benzopyran derivative of the general formula (I), or a salt thereof in an amount of 0.0C1 to 99.5 % and optionally other active ingredients in admixture with solid and/or liquid carriers and/or vehicles and/or surface active additives, preferably a dispersing, emulsifying or wetting agent and/or other auxiliary materials.

8. A fungicide, nematocide, acaricide, bactericide and insecticide composition which comprises as active ingredient a 4H-selenadia.zolo[5,4-c][1]benzothio- pyran derivative of the general formula (I), or a salt thereof in an amount of 0.001 to 99.5 % and optionally other active ingredients in admixture with solid and/or liquid carriers and/or vehicles and/or surface active additives, preferably a dispersing, emulsifying or wetting agent and/or other auxiliary materials.

9. A fungicide, nematocide, acaricide, bactericide and insecticide composition which comprises as active ingredient a 4H-thiadiazolo[5,4-c][1]benzo- pyran derivative of the general formula (I), or a salt thereof in an amount of 0.001 to 99.5 % and optionally other active ingredients in admixture with solid and/or liquid carriers and/or vehicles and/or surface active additives, preferably a dispersing, emulsifying or wetting agent and/or other auxiliary materials.

10. A fungicide, nematocide, acaricide, bactericide and insecticide composition which comprises as active ingredient a 4H-thiadiazolo[5,4-c][1]benzothio- pyran derivative of the general formula (I), or a salt thereof in an amount of 0.001 to 99.5 % and optionally other active ingredients in admixture with solid and/or liquid carriers and/or vehicles and/or surface active additives, preferably a dispersing, emulsifying or wetting agent and/or other auxiliary materials.

11. An acaricide composition, which comprises as active ingredient a compound of the general formula (I) or a salt thereof in an amount of 0.001 to 99.5 % and optionally other active ingredients in admixture with solid and/or liquid carriers and/or vehicles and/or surface active additives, preferably a dispersing, emulsifying or wetting agent and/or other auxiliary materials.

12. A fungicide, nematocide, acaricide, bactericide and insecticide composition, which comprises as active ingredient a compound of the general formula (I), wherein Q¹ is oxygen, Q² is selenium and R¹ as well as R² are each a methyl group, whereas R³ and n are as defined in claim 1 or a salt thereof in an amount of 0.001 to 99.5 % and optionally other active ingredients in admixture with solid and/or liquid carriers and/or vehicles and/or surface active additives, preferably a dispersing, emulsifying or wetting agent and/or other auxiliary materials.

13. A process for the preparation of the novel compounds of the general formula (I),

(I)

wherein R¹ and R² are independently from each other hydrogen, an unsubstituted or optionally suitably substituted alkyl or aryl group; or R¹ and R² together may be a cycloalkyl group; R³ is hydrogen; an optionally protected hydroxyl group; an alkyl, alkoxy, O-trialkyltio group; a phosphoric acid, thiophosphoric acid or phosphorous acid alkyl or aryl ester group connected through the oxygen atom; an acyloxy, acyloxyalkoxy, O-trialkylsilyl, aryloxy, alkenyloxy, alkynyloxy, cycloalkyloxy, cycloalkenyloxy, cycloalkylalkoxy group; an acyloxy or alkoxy group substituted by phosphoric acid, phosphonic acid or their esters; or two adjacent R³ groups together may represent: an -O-(CH₂)_m-O-group, wherein m is 1, 2, 3 or 4; or a condensed aromatic ring; or an -O-(CH₂)_m-(O)_z- group, wherein m is as defined above and z is 0 or 1; or an -O-P(Cl)- -O-, -O-P(OC_2H5)-O-, -O-P=O(OC₂H₅)-O-, -O-P=S(OC₂H₅)-O-, -O-(C=O)-O-, -O-(C=S)-O-, -O-P=O(SC₂H₅)-O-, -O-P=S(SC₂H₅)-O- or an -O-(S=O)-O- group; or a halogen or a haloalkyl, nitro, amino or suitably substituted amino group; an alkoxy group substituted by an alkylamino or a dial- kylamino group; or a nitrile, mercapto, optionally substituted alkylthio group; an optionally ring-substituted aralkyloxy group; an acyl group; or two adjacent R³ groups together may also represent a -C=C-C(=O)-O- and -C=C-C=(CH₃)₂-O- group; is 0, 1, 2, 3 or 4, and these R³ groups may have, independently from each other, any meaning defined for the R groups, Q¹ is oxygen, sulfur, SO or SO₂; Q² is sulfur or selenium as well as their salts having valuable biological effects which comprises transforming a compound of the general formula (IV),

(IV)

wherein R¹, R², R³, Q¹ and n are as defined above; and R⁴ is hydrogen, an aliphatic carboxylic acid ester group, an alkyl or aryl group, or a

-(C=O)-NH₂, -(C=S)-NH₂, -(C=O)-NH-NH₂, -(C=S)-NHNH₂, -(C=O)-NHR⁶. -(C=S)-NHR⁶, -(C=O)-NH-NHR⁶ , -(C=S)-NH-NHR⁶ , -(C=NH)-NH₂,

-(C=NH)-(NH-NH₂) or an -SO₂-R⁶ group; is an optionally substituted alkyl or aryl group or -(C=O)-NH₂ group;

to a benzopyran or benzothiopyran derivative of the general formula (I) and, if desired, converting the thus-obtained compound of the general formula (I) to a salt thereof.

14. A process for the preparation of the novel compounds of the general formula (I), wherein R¹, R², R³, Q¹, Q² and n are as defined in claim 13, which comprises transforming an appropriately substituted ketone of the general formula (II),

(II)

wherein R¹, R², R³, Q¹ and n are as defined in claim

12, with a suitable reactant of the general formula

(III)

H₂N-NH-R⁴

(III)

wherein R⁴ is as defined in claim 13, to a ketone derivative of the general formula (IV), wherein R¹, R², R³, R⁴, Q¹ and n are as defined in claim 13 and cyclizing the thus-obtained compound of the general formula (IV) by using a suitably selected selenium-containing reagent, preferably selenium dioxide.

15. A process for the preparation of the compounds of the general formula (IV), wherein R¹, R¹, R², R³, and n are as defined in claim 13 and Q¹ is oxygen, which comprises cyclizing a compound of the general formula (V),

(v)

wherein R¹, R², R³, R⁴ and n are as defined in claim 13, by using an acid.

16. A process for the preparation of the novel compounds of the general formula (I), wherein R¹, R², R³, Q¹, Q² and n are as defined in claim 13, which comprises reacting a compound of the general formula (VI),

(VI)

wherein R¹, R², R³, Q¹, Q² and n are as defined in claim 13, with a diazo-transfer reagent in the presence of a base and spontaneously cyclizing the thus-obtained non-isolated intermediate product.

17. A process for the preparation of the novel compounds of the general formula (I), wherein

R¹, R², R³, Q¹, Q² and n are as defined in claim 13, which comprises cyclizing a compound of the general formula (VII),

(VII)

wherein R¹, R², R³, Q² and n are as defined in claim

13, by using an acid, preferably acetic acid.

18. A process for the preparation of the novel compounds of the general formula (I), wherein R¹, R², R³, Q¹, Q² and n are as defined in claim 13, which comprises cyclizing a compound of the general formula (VIII),

(VIII)

wherein R¹, R², R³ , R⁵, Q¹, Q² and n are as defined in claim 13, through a non-isolated intermediate by using an alkaline reagent, preferably potassium hydroxide, sodium hydroxide or calcium hydroxide.

19. A process for the preparation of the novel compounds of the general formula (I), wherein

R¹, R², R³, Q¹, Q² and n are as defined in claim 13, which comprises reacting a coumarin derivative of the general formula (IX),

(IX)

wherein R³, Q¹, Q² and n are as defined in claim 13, with a Grignard reagent of the general formula R¹ MgX and/or R²MgX or a metal alkyl, wherein R¹ and R² are as defined In claim 13.

20. A process for the preparation of the compounds of the general formula (X),

(X)

which comprises cyclizing a ketone derivative of the general formula (IV), wherein one R³ means a chain connecting two ketones and R¹, R², R⁴, Q¹ and n are as defined in claim 13, by using an appropriately selected selenium-containing reagent, preferably selenium dioxide, selenous acid, selenites or selenium oxychloride.

21. A process for the preparation of the novel compounds of the general formula (I), wherein R¹, R², R³, Q¹ and n are as defined in claim 13, which comprises cyclizing a ketone derivative of the general formula (XI),

(XI)

wherein R¹, R², R³, Q¹ and n are as defined in claim 13 and R⁴ is for a C=O, C=S, or C=NH group.

22. A process for the preparation of the novel compounds of the general formula (I), wherein R¹, R², R³, Q², and n are as defined in claim 13, whereas

Q¹ is an SO or SO₂ group, which comprises oxidizing a compound of the general formula (I), wherein Q¹ means a sulfur atom and R¹, R², R³, Q² and n are as defined in claim 13.

23. A process as claimed in claim 13, which comprises cyclizing the compounds of the general formula (IV) by using selenium dioxide.

24. A process as claimed in claim 13, which comprises cyclizing the compounds of the general formula (IV) by using selenous acid.

25. A process as claimed in claim 13, which comprises cyclizing the compounds of the general formula (IV) by using selenites.

26. A process as claimed in claim 13, which comprises cyclizing the compounds of the general formula (IV) by using selenium oxychloride.

27. A process as claimed in any one of the claims 13, 15, 17, 20, 21, or 23 to 26, which comprises carrying out the cyclization in a C_1-6 aliphatic carboxylic acid, or in a mixture thereof, or in a mixture of such a carboxylic acid and an other solvent.

28. A process as claimed in any one of the claims 13, 20, 21 or 23 to 27, which comprises using the selenium-containing reagent in an amount of 1.0 to 1.5 equivalents.

29. A process as claimed in any one of the claims 13, 20, 21 or 23 to 28, which comprises carrying out the reaction resulting in a cyclization at a temperature of 0 to 120 °C, preferably at 20 to 80 °C.

30. A process as claimed in any one of the claims 13, 15, 17, 20, 21 or 23 to 29, which comprises obtaining the compound of the general formula (I), wherein R¹, R², R³, Q¹, Q² and n are as defined in claim 13 by evaporation and using repeatedly the thus-

-recovered solvent for the cyclization reaction.

31. A process as claimed in any one of the claims 13 to 29, which comprises obtaining the reaction product by filtration or extraction after pouring into water.

32. A process as claimed in claim 16, which comprises preparing the compounds of the general formula (I), wherein R¹, R², R³, Q¹, Q² and n are as defined in claim 13, by using tosyl azide in the presence of triethylamine.

33. A process as claimed in claim 16, which comprises carrying out the cyclization by using tosyl azide in the presence of trimethylamine.

34. A process as claimed in claim 16, which comprises carrying out the cyclization by using tosyl azide in the presence of morpholine.

35. A process as claimed in claim 16, which comprises carrying out the cyclization by using tosyl azide in the presence of N-methyl-piperidine.

36. A process as claimed in claim 16, which comprises carrying out the cyclization by using tosyl azide in the presence of piperidine.

37. A process as claimed in claim 16, which comprises carrying out the cyclization by using tosyl azide in the presence of phenyllithium.

38. A process as claimed in claim 16, which comprises carrying out the cyclization by using tosyl azide in diethylamine or in the presence of diethyl- amine.

39. A process as claimed in claim 16, which comprises carrying out the cyclization by using a diazo- -transfer reagent in the presence of an alkaline metal alkoxide.

40. A process as claimed in claim 16, which comprises using an appropriately selected organic nitrogen compounds as a base and/or as solvent.

41. A process as claimed in claim 16, which comprises using a diazo-transfer reagent differing from tosyl azide, preferably 4-azidosulfonylbenzoic acid.

42. A process as claimed in any one of the claims 16 or 32 to 39, or 41 which comprises using a C_1-6 alcohol, acetonitrile, a halogenated hydrocarbon, aliphatic ether, a cyclic ether, an organic base or an aprotic dipolar liquid as solvent.

43. A process as claimed in any one of the claims 16, or 32 to 42, which comprises carrying out the reaction at a temperature between 0 °C and 120 °C, suitably but not exclusively at 20 to 25 °C.

44. A process for the preparation of a fungicide, nematocide, acaricide, bactericide and insecticide composition, which comprises mixing as active ingredient a novel compound of the general formula (I), wherein R¹ , R², R³, Q¹, Q² and n are as defined in claim 13, or a biologically active salt thereof in an amount of 0.001 to 99.5 %, prepared as claimed in any one of the claims 13, 14, 16, to 19, 21 or 22 optionally with other active ingredients and solid and/or liquid carriers, and/or vehicles and/or surface active additives, preferably a dispersing, emulsifying or wetting agent and/or other auxiliary materials.