FR2606016A1 - Compounds of substituted 2H-2,4-dioxo-1,3,5-oxadiazine type, process for their preparation and their use for the preparation of phenoxybenzoic acid derivatives - Google Patents

Abstract

The invention relates to the compounds of formula I: in which: - A is OPr or - W is NO2, - X1, X2 are the oxygen atoms, - Z represents -N= or a group -C(X')= - X, X', Y, Y', Z' represent the hydrogen atom or a halogen atom or a NO2, CN or CF3 group, - R4 is an alkyl group. Use of these compounds for the preparation of phenoxybenzoic acid derivatives.

Description

 The invention relates to new compounds of substituted 2,4-dioxo 1,3,5-oxadiazine (2H) type, their preparation process and their use for the preparation of compounds derived from phenoxy benzoic acid. The invention also relates to the new compounds useful for the preparation of the abovementioned compounds.

The herbicidal properties of benzoic phenoxy acids or their derivatives are well known. French patent n 2t <9047 thus describes compounds of formula
VIII in which
- Z represents the nitrogen atom or a group -C (X
- W, Y, Y ', X, Z', X 'represent the hydrogen atom or a halogen atom or an NO2 or CN group or a polyhaloalkyl group such as CF3 or an alkyl or alkoxyl group, the various above-mentioned alkyl or alkoxyl groups most often having from 1 to 4 carbon atoms,
- Presents an alkyl group, optionally substituted, (for example by one or more halogen atoms and / or alkoxy groups) or an allyl or propargyl group.

 - X3 represents the oxygen or sulfur atom.

 - represents the hydrogen atom or an alkyl or cycloalkyl or phenyl group, this group being optionally substituted, (for example by one or more halogen atoms and / or alkoxy groups) or an allyl or propargyl group, or a alkylcarbonyl or alkylsulfonyl group.

 - R5 has one of the meanings given for R4 or represents a cation or a group OR6, R6 being the hydrogen atom, or a cation, or an alkyl group optionally substituted (for example by one or more halogen atoms and / or alkoxy groups).

It should be noted now that
- the formulas of the compounds have been grouped together at the end of the description and form an integral part of it.

 - the nomenclature indicated for these compounds is French, apart from the fact that the position of the substituents is indicated before the said substituents.

 An object of the invention is to provide new compounds allowing, in particular, the carrying out of a preparation process with improved yield and reaction conditions.

 Other objects of the invention will appear during the description which follows.

dans lequel X4 représente l'atome d'oxygène ou de soufre, et R7 représente l'atome d'hydrogene, ou un groupe alkyle ou phényle (ce groupe étant éventuellement substitué par un ou plusieurs atomes d'halogène et/ou groupes N02) ou un groupe X4R7 (X4 et R7 ayant la même signification que celle mentionnée ci-avant).Par exemple un groupe éthoxy carbonyle peut convenir.The invention therefore relates primarily to the compounds of formula I in which
either A is a group of formula XIV in which:
- Z represents the nitrogen atom or a group -C (X ') -,
- Y, Y ', X, Z', X 'represent the hydrogen atom or a halogen atom or an NO2 or CN group or a polyhaloalkyl group such as CF3 or an alkyl or alkoxyl group, the various alkyl groups or alkoxyl mentioned above most often having from 1 to 4 carbon atoms,
either A is an OPr group, Pr being a protective group, of the type

in which X4 represents the oxygen or sulfur atom, and R7 represents the hydrogen atom, or an alkyl or phenyl group (this group being optionally substituted by one or more halogen atoms and / or NO2 groups) or a group X4R7 (X4 and R7 having the same meaning as that mentioned above). For example an ethoxy carbonyl group may be suitable.

either A is a hydroxy group or an OM group, M being a metal cation (preferably an alkali or alkaline earth metal),
- W has one of the meanings of Y,
- R4 represents the hydrogen atom or an alkyl or cycloalkyl or phenyl group, this group being optionally substituted (for example by one or more halogen atoms and / or alkoxy groups), or an allyl or propargyl group, or a alkylcarbonyl or alkylsulfonyl group,
X X1 and X2, identical or different, represent the oxygen or sulfur atom.

The invention also relates to a process for preparing the compounds of formula I. This process consists of the following steps
a) VI -------- V
in the presence of a halogenating agent
b) V -------- t IV
in the presence of ammonia or ammonia
c) IV -------- III
in the presence of oxalyl chloride
d) III + Il --- 5 I.

In formulas II to VI mentioned above A,
Y, Y ', Z, X, Z', X ', X1, X2, W, R4, -M, Pr, X4, R7 have the same meaning as for formula I already described.

In the process according to the invention it is entirely possible at certain stages to transform the group
A. Thus it is possible to transform one of the compounds of formula IV and VI in which A corresponds to OPr into corresponding compounds where A is the group of formula XIV.

The latter are formed by dgprotecting the phenol function so as to obtain the corresponding phenol salt, in particular an alkali or alkaline earth metal salt, for example by the action of an organic or inorganic base then by reacting in a suitable solvent said salt with a derivative of formula VII in which Hal corresponds to a halogen atom and Z, Z ', X, X', Y, Y 'have the same meaning as that indicated for formula VIII.

When A is OH the compounds of formulas IV and VI can be prepared by bringing the compounds where A is OPr in the presence of an organic or inorganic base, the medium then being acidified for example using hydrochloric or sulfuric acid or phosphoric. We can also switch from phenols to the corresponding compounds where
A is the group of formula XIV by prior action of an organic or inorganic base, in order to obtain the compounds where A is OM, then by reaction of the salt as indicated above. The attachment of a protective group is carried out in a manner known per se, for example by esterification reaction.

 As typical examples of inorganic bases, mention may be made of sodium or potassium hydroxide, sodium or potassium carbonate, or others.

 As examples of organic bases, mention may be made of alkali metal or alkaline earth metal alcoholates, or others.

 An equivalent of organic or inorganic base is then necessary.

 In the case where one passes from OPr to OM and then to A of formula VIII, the phenol salts can optionally be prepared in a solvent different from that used for the reaction with the compound of formula VII. For example, the salts can be prepared in methanol. When a protic solvent such as methanol is used for the preparation of the salts, it may or may not be necessary to remove this solvent before the reaction with the derivative of formula IX begins. It is not necessary to prepare the phenol salts separately before carrying out the process according to the invention. It may be preferable, for example, to react the protected phenols with the compound VII in the presence of a base, for example a carbonate or an alkali metal hydroxide (such as sodium or potassium hydroxide or carbonate), so the phenol salts react with the compounds VII as they form in contact with the base.

 The reaction of the phenol salts with compound VII is usually carried out between 20 and 1800C, preferably between 60 and 1400C, in a polar aprotic solvent such as dimethylsulfoxide, dimethylformamide, tetramethylenesulfone, N-methylpyrrolidinone, hexamethylphosphoramide and dimethyl acetamide.

Generally, the phenol salts and compound VII are used in equimolar amounts, but an excess (up to 1.5 to 1) of either reagent can be used. Reaction times usually vary between 1 hour and 100 hours, preferably between 2 hours and 24 hours. When the reaction is complete, the product can be isolated by usual treatments.

 The phenols can be prepared from the compounds where A is OPr placed in the presence of an organic or inorganic base (as mentioned above), the reaction medium then being acidified, for example using hydrochloric acid or sulfuric or phosphoric.

Regarding the preparation process described above:
The reaction of step d) is advantageously carried out between 0 and 1200C in an inert solvent such as an aliphatic or aromatic hydrocarbon, optionally halogenated such as dichloromethane, 1,2-dichloroethane, toluene.

 The amount of isocyanate or isothiocyanate of formula II used is preferably between 1 and 5 moles for one mole of compound of formula III.

 Reaction c) is carried out between 0 and 1200C in the same solvents as those mentioned for reaction d) preferably in a molar ratio of oxalyl chloride: IV of between 1 and 1.2.

 Reaction b) is preferably carried out between 0 and 20 ° C. in the same solvents as those mentioned for reaction d) preferably in an ammonia: V molar ratio of between 2 and 2.1.

 Reaction a) is carried out in a known manner in the presence of one of the known halogenating agents; SOCl2, POC13, PCl3 may be cited, preferably between 20 and 1200C, in a halogenating agent: VI molar ratio of between 1 and 1.2.

 Preferably steps a), b), c), d) will be carried out with A equal to OPr, the transformation of A only taking place later.

The invention also relates to the use of the compounds of formula I for the preparation of compounds of formula VIII described above, apart from the fact that
R5 is the hydrogen atom. This use is characterized in that a compound of formula I is reacted with a compound of formula R3 X3H in which X3 and R3 have the meaning already indicated and in that in the case where A is different from formula XIV, we transform it into this said grouping.

The addition reaction of the compound of formula
R3X3H is advantageously carried out between 10 and 1500C, in an alcohol or thiol of formula R3X3H, in the presence or not of an alcoholate or thiolate of formula R 3X3M which can be used in catalytic amount up to the equimolar. The molar ratio I: R3X3H is advantageously between 0.01 and 1.

 The transformation of group A is carried out as indicated previously.

The present invention also relates to the compounds of formulas I, III, IV, in which A, X1,
X2, Y, Y ', X, X', Z, Z ', W, R4, M, Pr, X4, R7 have the same meaning as that indicated above.

The invention also relates to another process for the synthesis of the compounds of formula VIII already mentioned and described above, characterized in that a compound of formula IX is reacted in which
-R3 represents an alkyl group, this group being optionally substituted (for example by one or more halogen atoms and / or alkoxy groups), or an allyl or propargyl group.

- R4 represents the hydrogen atom or an alkyl or cycloalkyl or phenyl group, this group being optionally substituted, (for example by one or more halogen atoms and / or alkoxy groups) or an allyl or propargyl group, or a alkylcarbonyl or alkylsulfonyl group,
- R5 has one of the meanings given for R4 or represents a cation or a group OR6, R6 being the hydrogen atom, or a cation, or an optionally substituted alkyl group,
- X3 represents the oxygen or sulfur atom.

 - W represents the hydrogen atom or a halogen atom or an NO2 or CN group or a polyhaloalkyl group such as CF3 or an alkyl or alkoxyl group, the various above-mentioned alkyl or alkoxyl groups most often having from 1 to 4 carbon atoms.

 - A1 is OH, OM, M being a metal cation (preferably an alkali or alkaline earth metal), or OPr, Pr being a protective group, with a compound of formula VII described above.

 The operating conditions for transformation of group A as described above are directly applicable to this reaction.

It is thus possible to deprotect the OPr function so as to obtain the corresponding phenol salt, in particular an alkali or alkaline earth metal salt, for example by the action of an organic or inorganic base, then react the said salt with a derivative in an appropriate solvent. of formula
VII in which Hal corresponds to a halogen atom and
Z, Z ', X, X', Y, Y 'have the same meaning as that indicated for formula VIII.

The compound of formula VII can also be prepared by reacting a compound of formula X, in which
A1, W, X3, R3 have the same meaning as for the compound of formula IX, with phosgene so as to obtain in situ an intermediate of formula XI generally not isolated from the reaction medium.

The reaction is advantageously carried out between -30 and + 30 ° C. in a solvent, preferably an aliphatic or aromatic hydrocarbon, optionally halogenated, such as dichloromethane, 1,2-dichloroethane, toluene, chlorobenzene; one operates in the presence of an acid acceptor such as:
- the compound of formula X itself, in which case two molar equivalents of this compound are necessary for one molar equivalent of phosgene or
- a tertiary amine (for example 2,6-lutidine or 2,4,6-collidine).

The intermediate of formula XI is then reacted with a compound of formula
R5R4NH
so as to produce the compound of formula IX. The reaction is usually carried out between -30 and + 300C in an inert solvent and in the presence of an acid acceptor such as
- a tertiary amine (for example triethylamine or pyridine), or
- the compound of formula R5R4NH itself, in which case two molar equivalents of this compound are necessary for one molar equivalent of compound of formula XI.

 The solvent is generally the same as that in which the compound of formula XI has been prepared.

The compounds of formula X are prepared using methods known per se (see in particular: S. PATAI, "The
Chemistry of Amidines and Imidates ", 1975, Interscience publication, John WILEY and sons).

 For example by 0 or S-alkylation of benzamides or thiobenzamides of formula XII using an alkylating agent such as a dialkyl sulfate, or a trialkyloxonium salt, or an alkyl fluorosulfonate, or others.

 The reaction is usually carried out, between 0 and 120 C, in an inert solvent such as an aliphatic or aromatic hydrocarbon, optionally halogenated such as dichloromethane, 1,2-dichloroethane, toluene.

 The alkyl benzimidates or thiobenzimidates can then be released from their salts of formula XIII in which R3, X3, W, M, Pr, A1, X4, 7 have the same meaning as above and Q represents a halide anion, in particular chloride, bromide, iodide, or a tetrafluoroborate anion, or other various anions derived from protonic acids, in particular strong acids, according to methods known per se, for example by the action of a mineral base such as a hydroxide or a carbonate alkaline, in a solvent medium, most often simply at room temperature.

The invention also relates to a process for the preparation of the compounds of formula XV as described above in which
- Z represents the nitrogen atom or a group -C (X ') =,
- W, Y, Y ', X, Z', X 'represent the hydrogen atom or a halogen atom or an NO2 or CN group or a polyhaloalkyl group such as CF3 or an alkyl or alkoxyl group, the various above-mentioned alkyl or alkoxyl groups most often having from 1 to 4 carbon atoms,
-R3 represents an alkyl group, optionally substituted, (for example by one or more halogen atoms and / or alkoxy groups) or an allyl or propargyl group.

 - X2, X3 represent the oxygen or sulfur atom.

 - R4 represents the hydrogen atom or an alkyl or cycloalkyl or phenyl group, this group being optionally substituted, (for example by one or more halogen atoms and / or alkoxy groups) or an allyl or propargyl group, or a alkylcarbonyl or alkylsulfonyl group.

 - R5 represents the hydrogen atom.

 It is characterized in that a compound of formula II as defined above is reacted with a compound of formula X as defined above.

This latter reaction is advantageously carried out between 10 and 1500C in an inert solvent such as an aliphatic or aromatic hydrocarbon, optionally halogenated, or an ether, or a nitrile, and in the presence or not of a catalyst. As catalysts, there may be mentioned without limitation
- tertiary amines such as triethylamine, pyridine, N, N-dimethylaniline and
N, N-diethylaniline, 1,4-diazabicyclo (2,2,2) octane, or
- tin derivatives, and in particular alkyltin salts such as dibutyltin diacetate, or dibutyltin dilaurate.

 The isocyanates or isothiocyanates of formula II are prepared according to methods known per se.

 In the case where A is different from formula XIV, A is transformed into this group as described above.

The invention also relates to the compounds of formulas IX to XIII in which A1, R3, R4, R5,
W, X3, M, Pr, Q, X4, R7 have the meaning mentioned above.

 The examples below illustrate the invention without, however, limiting it.

Example 1: Preparation of 5-ethoxyearbonyloxy-2-nitro-benzamide. A solution of 600 g (2.35 moles) of 5-ethoxycarbonyloxy-2-nitro-benzoic acid in 1300 cm3 of 1,2-dichloroethane, supplemented with 2 cm3 of dimethylformamide, is heated to reflux of the solvent. Then poured dropwise, with stirring, 446 g (3.75 moles) of thionyl chloride. At the end of the pouring, the mixture is allowed to stir, at reflux of the solvent, until the end of the gaseous evolution of SO 2 and HCl (approximately 1 hour 15 minutes).

The reaction mixture is then allowed to cool to ambient temperature, then the excess of thionyl chloride and the solvent are removed on a rotary evaporator. The residue is dissolved in 5000 cm3 of dichloromethane. The solution is stirred, then 80 g (4.7 moles) of ammonia are introduced, while maintaining the reaction medium at a temperature below 300C. At the end of the addition, the reaction medium is stirred for 1 hour at room temperature. 1000 cm3 of water are added, then the inorganic phase is separated, before washing with 2 times 1000 cm3 of 5% HCl, then with 2 times 1000 cm3 of water. The chloromethylenic phase is dried over magnesium sulphate, then concentrated on a rotary evaporator. This gives 320 g (yield 64
Z) of a white solid of 5-ethoxycarbonyloxy-2nitro-benzamide melting at 149 "C.

Example 2: Preparation of 6- (5'-ethoxycarbonyloxy-2'-nitro-phenyl) -3-methyl-3,4-dihydro -2,4-dioxo-1,3,5-oxadiazine (2H).

A suspension of 20.3 g (0.08 mole) of 5-ethoxycarbonyloxy2-nitro-benzamide in 175 cm3 of dichloromethate is heated to reflux of the solvent. 11.2 g (0.088 mole) of oxalyl chloride are poured in dropwise with stirring.

At the end of the pouring, the stirring is continued, at the reflux of the solvent, until the end of the gaseous evolution of CO and HCl (about 2 hours). Then poured dropwise, with stirring, 15.4 g (0.27 mole) of methyl isocyanate and the stirring is continued for 24 hours at reflux of the solvent. The reaction mixture is allowed to cool to ambient temperature, then the excess oxalyl chloride, methyl isocyanate and the solvent are removed on a rotary evaporator. The residue is taken up in 200 cm3 of ether. The precipitate formed is filtered, washed with ether and dried. 11.5 g are thus obtained (yield 43 Z) of a white solid of 6- (5'-ethoxycarbonyloxy-2'-nitro-phenyl) -3-methyl-3,4-dihydro-2,4-dioxo- 1,3,5-oxadiazine (2H) melting at 133 "C.

Example 3: Preparation of methyl 5-ethoxycarbonyloxy-2-nitro-N- (N '-methyl carbamoyl) -benzimidate.

A suspension of 10.1 g (0.03 mole) of 6- (5'-ethoxyearbonyloxy-2'-nitro-phenyl) -3-methyl-3,4-dShydro -2,4-dioxo-1,3, 5-oxadiazine C2H) in 100 cm3 of methanol is heated with stirring at reflux of the solvent, until the end of the evolution of CO 2 gas (approximately 2 hours). The reaction mixture is allowed to cool to room temperature, then the methanol is removed on a rotary evaporator. The residual solid is taken up in 100 cm3 of ether, filtered and dried. 7.4 g (76% yield) of a white solid of methyl 5-ethoxycarbonyloxy-2-nitro-N- (N '-methyl carbamoyl) -benzimidate, melting at 132 ° C., are thus obtained.

Example 4: Preparation of methyl 5- (3'-chloro-5'-trifluoromethyl-2'-pyridyloxy) -2-nitro-N- (N'-methylcarbamoyl) -benzimidate.

A solution of 3.25 g (0.01 mole) of methyl 5-ethoxycarbonyloxy-2-nitro-N- (N '-methyl carbamoyl) -benzimidate and 0.66 g is allowed to stir for 30 minutes at room temperature. 0.01 mole) of potash at 85% in 10 cm3 of methanol. Then added 50 cm3 of dimethyl sulfoxide and 2.37 g (0.011 mole) of 2,3-dichloro-5-trifluoromethyl-pyridine. The reaction mixture is then heated for 24 hours at 100 ° C., then cooled to room temperature. The methanol and the dimethyl sulfoxide are removed on a rotary evaporator.

The residual yellow oil is taken up in 50 cm3 of dichloromethane and the resulting solution is washed with 2 times 20 cm3 of water, then dried over magnesium sulphate and concentrated on a rotary evaporator. The residue is taken up in 10 cm3 of methanol. The precipitate formed is filtered, washed with methanol and dried. 2.3 g (54% yield) are thus obtained of a white solid of 5- (3'-chloro-5'-trifluoromethyl-2'-pyridyloxy) -2-nitro-N (N'-methylcarbamoyl) -benzimidate methyl melting at 1700 C.

Claims (10)

1) Compounds of formula I as indicated at the end of the  description in which  either A is a group of formula XIV in which  - Z represents the nitrogen atom or a group  - Y, Y ', X, Z', X 'represent the hydrogen atom or a halogen atom or a NO2 or CN group or a polyhaloalkyl group such as CF3 or an alkyl or alkoxyl group, the various alkyl groups or alkoxyl mentioned above most often having from 1 to 4 carbon atoms,  either A is an OPr group, Pr being a protective group, for example an ethoxy carbonyl group,  either A is a hydroxy group or an OM group, M  being a metal cation (preferably of a  alkali or alkaline earth metal),  - W has one of the meanings of Y,  - R4 represents the hydrogen atom or an alkyl or cycloalkyl or phenyl group, this group being optionally substituted, (for example by one or more halogen atoms and / or alkoxy groups) or an allyl or propargyl group, or a alkylcarbonyl or alkylsulfonyl group,  - X1 and X2, identical or different, represent the oxygen or sulfur atom. 2) Process for the preparation of the compounds according to  claim 1, characterized in that it consists in  the following steps a) VI ------- v V  in the presence of a halogenating agent b) V ----- 4 IV  in the presence of ammonia or ammonia c) IV ------- III  in the presence of oxalyl chloride  d) III + II --- + I,  and in that in the formulas II to VI mentioned  above A, Y, Y ', X, Z, Z', X ', X1, X2, W, R4,  M, Pr have the same meaning as for formula I of  claim 1) and in that A is the same or  different for the different stages. 3) Method according to claim 2) characterized in that  the compound of formula I after reaction d) has a  group A which is OPr. 4) Method according to one of claims 2 or 3,  characterized in that the reaction of step d) is  carried out between 0 and 1200C, in an inert solvent and in  that the molar ratio II: III is between 1  and 5. 5) Method according to one of claims 2 or 3,  characterized in that the reaction of step c) is  carried out between 0 and 1200C, in inert solvent. 6) Method according to one of claims 2 or 3,  characterized in that the reaction of step b) is  performed at a temperature between 0 and 200C. 7) Use of the compounds according to claim 1) for  the preparation of compounds of formula VIII in  which :  - Z represents the nitrogen atom or a group -C (X ') =,  - W, Y, Y ', X, Z', X 'represent the hydrogen atom  or a halogen atom or a NO2 or CN group or a  polyhaloalkyl group such as CF3 or an alkyl group  or alkoxyl, the various alkyl or alkoxyl groups  aforementioned having most often from 1 to 4 atoms of  carbon,  - R3 represents an alkyl group, optionally  substituted, (for example by one or more atoms  halogen and / or alkoxy groups) or an allyl group or  propargyle.  - X3 represents the oxygen or sulfur atom.  or alkylsulfonyl.  allyl or propargyl group, or an alkylcarbonyl group  several halogen atoms and / or alkoxy groups) or one  optionally substituted, (for example by one or  alkyl or cycloalkyl or phenyl, this group being  - R4 represents the hydrogen atom or a group  group.  different from formula XIV, we transform it into said  formula VIII and in that, in the case where A is  which X3 and R3 have the meaning indicated in the  formula I with a compound of formula R 3X3 H in  characterized in that a compound of  - R5 is a hydrogen atom, 8) Use according to claim 7), characterized in  what the I: R 3X3 H molar ratio is understood  between 0.01 and 1, and / or the temperature is between  10 and 1500C, possibly in the presence of an alcoholate  or thiolate of formula R3X3M. 9) Use according to claim 7), characterized in  what A is transformed from OPr into a group of formula XIV-,  the temperature of the condensation reaction being  between 20 and 180 "C and carried out in a solvent  aprotic polar. 10) Compounds of formulas I, III, IV, in which Pr,  X1, X2, W, A, X, X ', Y, Y', Z, Z ', R4, have the same  meaning as that indicated in claim 1).