US3622630A - 10-aminoalkyl-9,10-dihydroanthracenes - Google Patents

Abstract

10-Aminoalkyl-9,10-dihydroanthracenes wherein the nucleus is substituted by halogen, lower alkyl, trifluoromethyl, lower alkylthio, lower alkylsulfonyl or N,N-dimethyl-sulfamyl and the amino group may be mono or dialkyl substituted as well as a monocyclic heterocyclic amino moiety are tranquilizers. Corresponding 9-lower alkyl or 9-phenyl derivatives also have utility as antidepressants. Compounds are generally prepared by reaction of a 10-bromoalkyl-anthracene with an appropriate amine followed by reduction to the 9,10-dihydroanthracene. 9-Substituted-10-aminoalkyl-9,10-dihydroanthracenes which are not benzo ring substituted have antidepressant activity with no tranquilizing activity. These compounds are generally prepared by alkylation of the 9,10-dihydroanthracene with an aminoalkyl halide.

Description

United States Patent [72] Inventors Paul N. Craig Ambler; Charles L. Zirkle, Berwyn, both of Pa.

[2!] Appl. No. 742,171

[22] Filed July 3, 1968 [45] Patented Nov. 23, 1971 [73] Assignee Smith, Kline 8: French Laboratories Philadelphia, Pa. Continuation-impart of application Ser. No. 631,584, Apr. 18, 1967, now abandoned Continuation-impart of application Ser. No. 526,975, Feb. 14, 1966, now abandoned. This application July 3, 1968, Ser. No. 742,171

[54] 10-AMlNOALKYL-9,IO-DIHYDROANTHRACENES 24 Claims, No Drawings [51] Int. Cl C07d 87/28 [50] Field of Search 260/570.8

TC,501.l,501.l2, 343.7,253,570.8, 501.1. 50l.l2,32l,253

[56] References Cited UNITED STATES PATENTS 7/ l 946 Cusic OTHER REFERENCES Davis et a1. .lour. Med. Chem," Vol. 7, pages 88- 90 (1964) Mjchajlyszyn et al., Coll. Czech. Chem. Comm.," Vol. 24, pages 3955- 3956 1957) Primary Examiner-Robert V. Hines Attorneys-William H. Edgerton, Richard D. Foggio, Joan S. Keps, Arthur R. Eglington, Aland D. Lourie and Joseph A. Marlino ABSTRACT: l0-Aminoalkyl-9, l O-dihydroanthracenes wherein the nucleus is substituted by halogen, lower alkyl, trifluoromethyl, lower alkylthio, lower alkylsulfonyl or N,N- dimethyl-sulfamyl and the amino group may be mono or dialkyl substituted as well as a monocyclic heterocyclic amino moiety are tranquilizers. Corresponding 9-l0wer alkyl or 9- phenyl derivatives also have utility as antidepressants. Compounds are generally prepared by reaction of a IO-bromoalkyl-anthracene with an appropriate amine followed by reduction to the 9, l O-dihydroanthracene.

9-Substituted- I 0-aminoalkyl-9, I O-dihydroanthracenes which are not benzo ring substituted have antidepressant activity with no tranquilizing activity. These compounds are generally prepared by alkylation of the 9,l0dihydroanthracene with an aminoalkyl halide.

lO-AMINOALKYL-9, IO-DIHYDROANTHRACENES This application is a continuation-in-part of application Ser. No. 631,584 filed Apr. l8, i967 and now abandoned which is a continuation-in-part of application Ser. No. 526,975 filed Feb. 14, 1966 and now abandoned.

This invention relates to novel substituted IO-aminoalkyl- 9,10-dihydroanthracenes which have useful phamiacodynamic properties. More specifically the novel products of this invention effect the central nervous system and have utility as tranquilizers. The tranquilizing activity is demonstrated in standard pharmacological test procedures employed in characterizing chlorpromazine and trifluoperazine at oral dosages in rats, mice and monkeys approximately equivalent to the latter agents.

The novel l-aminoalkyl-9,lO-dihydroanthracenes of this invention are represented by the following general structural formula:

5 ICE 4 6 9 3 FORMULA i when:

R represents hydrogen, lower alkyl, such as methyl or ethyl, or phenyl;

Y represents halogen having an atomic weight of less than 80, preferably chlorine, lower alkyl such as methyl, trifluoromethyl, lower alkylthio such as methylthio, lower alkylsulfonyl such as methylsulfonyl or N,N-dimethyl-sulfamyl;

A represents an alkylene chain, straight or branched, of from two to four carbon atoms, and

2 represents amino, mono-loweralkylamino, di-loweralkylamino, or a monocyclic heterocyclic amino moiety containing from four to 12 carbon atoms, and containing a maximum of two hetero ring members selected from the group of oxygen, nitrogen and sulfur, such as particularly morpholinyl, thiamorpholinyl, N-pyrrolidinyl, N-piperidinyl, n-lower-alkyl- N-piperazinyl, N-(w-hydroxy-lower-alkyl)-N-piperazinyl, N'- (w-hydroxy-alkoxy-lower-alkyl)-N-piperazinyl or N'-(wacetoxy-lower-alkyl)-N-piperazinyl.

Advantageous compounds of this invention are represented by the following formula:

( JHzCHCHr-Z FORMULA ll Particularly advantageous compounds are 10-(3- dimethylaminopropyl )-2-trifluoromethyl-9, l 0- dihydroanthracene and 9-methyl- 10-(3- dimethylaminopropyl)-2-trifluoromethyl-9,l0- dihydroanthracene.

Compounds of formulas l and ll above wherein R is lower alkyl or phenyl, in addition to having tranquilizing activity,

also have utility as antidepressants. The antidepressant activity is demonstrated in standard pharmacological test procedures employed in characterizing imipramine and amitryptyline at oral dosages in mice and rats approximately equivalent to the latter agents.

By the terms lower alkyl or alkoxy where used herein alone or in combustion with other terms, groups having from one to four, preferably one to two carbon atoms are indicated.

This invention also includes stable, pharmaceutically acceptable, acid addition salts of the above defined bases formed with nontoxic organic and inorganic acids. Such salts are easily prepared by methods known to the art. The base is reacted with either the calculated amount of organic or inorganic acid in aqueous miscible, solvent such as acetone or ethanol, with isolation of the salt by concentration and cooling or an excess of the acid in aqueous immiscible solvent, such as ethyl ether or chlorofon'n, with the desired salt separating directly. Exemplary of such organic salts are those with maleic, fumaric, benzoic, ascorbic, pamoic, succinic, bismethylenesalicyclic, methane-sulfonic, ethanedisulfonic, acetic, propionic, tartaric, salicylic, citric, gluconic, lactic, malic, mandelic, cinnamic, citraconic, aspartic, stearic, palmitic, itaconic, glycolic, paminobenzoic, glutamic, benzene sulfonic and theophylline acetic acids as well as with the 8chlorotheophylline and 8- bromotheophylline. Exemplary of such inorganic salts are those with hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, and nitric acids. These salts may also be prepared by the classical method of double decomposition of appropriate salts which is well known to the art.

The l0-aminoalkyl-9,lO-dihydroanthracenes of this invention are prepared by one of several routes depending on the nuclear (Y) substituent and the presence of a 9-alkyl or phenyl group. When the 9-position is unsubstituted (R=H) the products are obtained advantageously via the fully aromatic anthracenes which are prepared as shown in the following synthetic scheme illustrated by way of example for 2 represented by dimethylamino:

(L) HO A -O CH;

HN CH) Y a 2 CHzO-A-MgX lHBr FORMULA ill in which Y AND A are as defined in Formula l and X is halogen, preferably chlorine.

According to the above procedure, the substituted anthrone is reacted with a methoxyalkyl magnesium halide to give the lO-methoxyalkyll O-hydroxy-9, l O-dihydroanthracenes. Advantageously the reaction is carried out in an inert organic solvent such as ether, for example diethyl ether, dioxane or, preferably, tetrahydrofuran at a temperature of from about 0 C. to room or ambient temperature for a period of about 3 to 24 hours. Removal of the solvent and treatment of the residue with water and/or an ammonium salt solution separates the lO-methoxyalkyl derivative. The latter is treated with concentrated (48 percent) hydrobromic acid to give simultaneous dehydration of the IO-hydroxy group and cleavage of the methyl ether linkage. The resulting lO-bromoalkylanthracenes are treated with a di-loweralkylamine as shown above or ammonia, a mono-loweralkylamine, pyrrolidine, piperidine, N-lower alkyl-piperazine or N-( w-acetoxy-lower-alkyl)-piperazine to give the corresponding aminoalkylanthracenes of formula [11. The latter useful intermediates are reduced to give the 9,l0-dihydroanthracene products of this invention with phosphorus and hydrogen iodide or with hydrogen and copper chromite catalyst when Y is trifluoromethyl.

Hydrolysis of the Nacetoxyalkyl-N-piperazinyl products thus formed with for example sodium hydroxide solution yields the corresponding N'-(m-hydroxy-lower-alkyl)-N- piperazinyl derivatives of Formula I. Further alkylation of the N-piperazinyl compounds thus obtained with an alkylene oxide or alkylene halohydrin yields other N'-substituted piperazinyl compounds of formula I.

The 9-unsubstituted anthrone starting materials used as above are either known or prepared conveniently as illustrated by the following outline of the preparation of 2- trifluoromethyl-lOanthrone. Phenyl magnesium bromide is reacted with 2bromo-4-trifluoromethylbenzonitrile to give 2- bromo-4-trifluoromethylbenzophenone. The latter is reduced with for example phosphorus and hydrogen iodide to yield 2- bromo-4-tritluoromethyl-diphenylmethane, which is reacted first with magnesium, then with carbon dioxide to give 2- benzyl-5trifluromethylbenzoic acid. Cyclization by acid treatment with for example concentrated sulfuric acid furnishes the 2-trifluoromethyll O-anthrone.

The compounds of formula I when R is lower alkyl or phenyl and especially when Y is trifluoromethyl are prepared as shown in the following sequence illustrated by way of example for R is methyl and Z is dimethylamino:

According to the above procedure. the substituted 2-(amethylbenzyl)-benzonitrile is reacted with a methoxyalkyl magnesium halide as described more fully hereinabove to give the methoxyalkyl imine derivative. The latter is treated with concentrated (48 percent) hydrobromic acid to simultaneously ring close and cleave themethyl ether linkage The resulting lO-bromoalkyl-anthracene is treated with the appropriate amine to give the corresponding lO-aminoalkylanthracene which is reduced with, preferably, hydrogen and copper chromite catalyst to the 9-alkyl-9,l0 dihydroanthracene product.

The benzonitrile starting materials used as above are either known or prepared conveniently as illustrated by the following outline of the preparation of 2-(a-methylbenzyl)5- trifluoromethylbenzonitrile. 2-Bromo-4-trifluoromethylbenzophenone is reacted with a tri-loweralkyl sulfoxonium halide such as trimethylsulfoxonium iodide in a suitable organic solvent for example dimethyl sulfoxide is usually in the presence of a strong alkali such as an alkali metal hydride, i.e. sodium or potassium hydride or an alkali metal lower alkoxide such as sodium methylate or ethylate to give l-phenyl-l-( 2- bromo-4-trifluoromethylphenyl)-ethylene oxide. The latter is reduced with a bimetallic hydride such as lithium aluminum hydride in a suitable nonpolar organic solvent such as ethyl ether or tetrahydrofuran to a-phenyl-a-(2-bromo-4- trifluoromethylphenyl)-ethanol. This alcohol is then reduced with phosphorus and hydrogen iodide to 2-(a-methylbenzyl)- 5trifluoromethyl-bromobenzene which is treated with cuprous cyanide to give the corresponding benzonitrile. Alternatively, this benzonitrile may be hydrolyzed to the benzoic acid and cyclized with for example 9acid to give 9-methyl- 2- trifluoromethyl-lO-anthrone which may be converted to products of this invention as described hereinabove.

Either of the two general procedures described above for the preparation of compounds of formula I may be interchanged. For example, 2-bromo-4-trifluoromethyldiphenylmethane is converted with cuprous cyanide to the 2-benzyl- S-trifluoromethylbenzoitrile which is then reacted with a methoxyalkyl magnesium halide to give the imine followed by similar reactions as described above to furnish the corresponding 9-unsubstituted-9, l O-dihydrozinthracene products.

Some of the compounds of this invention may be present as cis or trans isomers as well as mixtures of these isomers. For example, when R in formula I is other than hydrogen the geometrical isomers may be represented as follows:

E R R. H

H A-Z H AZ The isomers are separated by fractional crystallization of their acid addition salts from a suitable solvent or mixture of solvents such as, for example, acetone-ether or ethanol-ether, Also, a pure isomer may be obtained directly from the reduction of the IO-aminoalkyl anthracene.

In addition, it will be readily apparent to one skilled in the art that certain compounds of this invention may be present as optical isomers. These isomers are separated by recrystallization of the optically active acid addition salts, for example the d-and l-di-p-toluoyltartrates of the racemic free base. Alternatively, a precursor in the synthesis of the products of formula I may be resolved into d-and l-isomers and the separated isomers reacted further to give the optically active products.

The connotation of the general formulas presented herein is to include all isomers, the separated d or 1 optical isomers as well as the a l mixture and the separated cis or trans isomers as well as the mixture of these isomers.

A useful pharmacological indicator of tranquilizing activity is the production of ptosis in rats. In this procedure rats are examined after oral administration of a test compound at hourly intervals for a ptotic efiect and the incidence of ptosis is recorded as a percentage of the number of test animals. Another test procedure for evaluating tranquilizing activity is the suppression of rage in mice. A test compound is administered orally to mice preselected for their ability to exhibit rage episodes during footshock and the animals are tested again. The percentage of animals exhibiting protection against rage is recorded.

Antidepressant activity is measured pharmacologically by the ability of a compound to prevent reserpine-induced ptosis in rats or mice. In this procedure a test compound is administered orally to the animals followed at various time intervals by l mg./kg. of reserpine (iv) and the test animals are observed 45 minutes thereafter for ptosis prevention.

The following table 1 sets forth comparative data obtained by employing the above described test procedures for selected compounds of this invention and the closest known prior art l0-aminoalkyl-9, l O-dihydroanthracenes.

TABLE 1 Oral Rat ptosis, drse, maximum percent In g ire e Pro- Pro- Compound base) duction vention A 29 0.... m 29 B-. CH CH; 44 45.4

(CHz)a-' (CH:4)2

Austria 223,611

C 2. 7 5. 4 10. 8 21. 6 75. 0 C Fa ED50=1L1 mg./kg.

(CHr)iN( Ha)1 D Cis isomer H CH: 30 30 10 50 80 43. 4 80 C F a ED50=14.5 IngJkg.

H (CF2)aN(CH:)z

From the above table it is observed that the prior art compounds A and B are either inactive or demonstrate activity at doses considerably higher than compounds C and D of the invention.

In general the separated !-isomer of a racemic compound of this invention is more active phannacologically than corresponding racemic mixture as illustrated in table 2 for tranquilizing activity.

As noted hereinabove the compounds of formulas l and ll wherein R is lower alkyl or phenyl have both tranquilizing and antidepressant activity. Thus the compound D in table 1 has an ED of 14.5 mg./kg. in the rat ptosis prevention test (antidepressant activity) and the same compound B (dl-isomer) in table 2 has an ED of 32.1 mg./kg. in the mouse suppression test (tranquilizing activity). To demonstrate that compounds of formulas l and ll when R is hydrogen do not have antidepressant activity, test results are shown in table 3 for mouse ptosis prevention.

Thus. although the parent compound A shown in table 3 has no antidepressant activity, the presence of a 9-methyl substituent in compound B incorporates a component of antidepressant activity while retaining the already present tranquilizing activity of the parent compound A.

A further aspect of this invention relates to 9-substitutedlO-aminoalkyl-Q,lO-dihydroanthracenes which are not benzo ring substituted. These compounds have antidepressant activity with no tranquilizing activity. The antidepressant activity is demonstrated in standard phannacological test procedures employed in characterizing imipramine and amitryptyline at oral dosages in mice and rats approximately equivalent to the latter agents. These 9-substituted-lO-aminoalkyl-9,l0- dihydroanthracenes are represented by the following general structural formula:

ill: 0 H

(I l-I A Z Formula IV when.

R represents lower alkyl. such as methyl or ethyl, or phenyl; and

A and Z are as defined in formula I above.

The compounds of the formula IV are prepared ad vantageously by direct alkylation of an R -substituted-9.l0- dihydroanthracene with a tertiary aminoalkyl halide, such as dimethylaminopropyl chloride, in an inert organic solvent. for example dimethylsulfoxide or an ether Preferably an alkali metal salt of the 9,10-dihydroanthracene is employed which is prepared for example from the sodium hydride or butyl lithi um. Alternatively, methods analogous to those described for the preparation of compounds of formula I above may be employed to obtain compounds of fonnula lV Similarly these compounds may be present as cis, trans isomers which are separated by fractionation Also, a pure cis isomer upon treat ment with sodium hydride m dimethylsulfoxide gives a mixture of cis, trans isomers from which the pure trans isomer IS separated.

In contrast to the compounds of formulas I and 11 wherein R is lower alkyl or phenyl which have both tranquilizing and antidepressant activity, the compounds of formula [V which share the structural feature of 9-substituent but lack the benzo ring substituent have antidepressant activity but no tranquilizing activity. This is shown in the following table 4.

The novel compounds of this invention may be administered orally or parenterally in conventional dosage unit forms such as tablets, capsules, injectables or the like, by incorporating the appropriate dose of compound of formula 1 or IV with carriers according to accepted pharmaceutical practices. In practice, unit doses of from 10 mg. to 250 mg. administered from one to four times a day are effective.

The following examples are not limiting but are illustrative of compounds of this invention and procedures for their preparation and will serve to make fully apparent all of the compounds embraced by the general formulas given above. Alternatives and modifications of the general procedures set forth herein will be apparent to those skilled in the art.

EXAMPLE 1 A mixture of 12.7 g. of magnesium and 56.7 g. of 3-methoxypropyl chloride in 300 ml. of ether is refluxed for 1 hour. The resulting mixture is cooled to about 10 C. and a suspension of 34.3 g. of 2-chloro-l0-anthrone in 250 m1. of ether is added. The reaction mixture is allowed to warm to room temperature and stand overnight. Most of the ether is removed and the residue decomposed with ammonium sulfate in a minimum of water plus ice. The mixture is extracted with ether, the extract evaporated and the residue taken up into benzene. The benzene is extracted with alkali and then evaporated to give 2- chlorol O-hydroxyl -3-methoxypropyl )-9, l 0- dihydroanthracene.

A solution of 28.7 g. of the above 9,10-dihydroanthracene in 1 ml. of 48 percent hydrobromic acid and 225 ml. of glacial acetic acid is refluxed for 6 hours. The reaction mixture is then concentrated, diluted with water and made strongly alkaline. The solution is extracted with ether and the dried extract is chromatographed on alumina to give 2-chloro-l0-( 3- bromopropyl)-anthracene, m.p. 77-78 C.

Into a solution of 10.0 g. of the above anthracene in 30 ml. of benzene is bubbled about 12 g. of dimethylamine at room temperature. The resulting mixture is heated in a pressure bottle on a steam bath for 4 hours, cooled and allowed to stand. The reaction mixture is made basic, treated with ether and filtered. The separated, dried ether solution is evaporated to give 2-ch1orol 0-( 3-dimethylaminopropyl )-anthracene; hydrochloride salt, m.p. 234235 C.

A mixture of 2.0 g. of the above salt free base and 2.0 g. of red phosphorus in 10 ml. of 57 percent hydroiodic acid is refluxed for 24 hours The reaction mixture is diluted with water, filtered, made basic and extracted with ether to give 2' chlorol 0-( 3-dimethylaminopropyl)-9. l O-dihydroanthracene; hydrochloride salt, m.p. l-203 C EXAMPLE 2 A mixture of 18.2 g. of 2-chloro-l0( 3- bromopropyl)anthracene (prepared asin example 1 and l 1.0 g. of N-methylpiperazine in 50 ml. of toluene is refluxed for 24 hours. The reaction mixture is made basic and extracted with ether to give 2-chloro-10-[3-(N'-methyl-N-piperazinyl)-- propyll anthrancene; hydrochloride salt, m.p. 260 C. dec.

A mixture of 2.0 g. of the above free base and 2.0 g. of red phosphorus in 10 ml. of 57 percent hydroiodic acid is refluxed for 24 hours. The reaction mixture is diluted, filtered and made basic to give 2-chloro-l0-l 3-(N-methyl-N-piperazinyl)- propyll-9,lO-dihydroanthracene; hydrochloride salt, m.p. 233 C. dec.

Similarly, by employing an equivalent amount of dibutylamine instead of N-methypiperazine in the above sequence, there is obtained 2-chloro-l0-( 3-dibutylaminopropyl)-9.l0- dihydroanthracene.

EXAMPLE 3 To a solution of 20 g. of 2-bromo-4-trifluoromethylbenzonitrile in 300 ml. of ether is added 29 ml. of a 3M solution of phenylmagnesium bromide in 100 ml. of ether and the resulting mixture is refluxed for 3 hours, then stirred for 16 hours at room temperature. The dried ether solution is evaporated and the residue treated with excess dilute hydrochloride acid to give the imine which is heated on the steam bath for l hour. This mixture is extracted with ether to give after fractional distillation, 2-bromo-4-trifluoromethylbenzophenone, m.p. 52-53 C.

A mixture of 12.5 g. of the above benzophenone and 12.5 g. of red phosphorus in 25 ml. of 57 percent hydroiodic acid is refluxed and stirred under nitrogen for 24 hours. The reaction mixture is diluted with water, filtered and solid washed with ether and water. The ether solution is dried and evaporated to give 2-bromo-4-trifluoromethyldiphenylmethane, b.p. 97-l00 C./0.'2 mm.

The Grignard reagent prepared from 5.0 g. of the above diphenylmethane and 0.4 g. of magnesium in 50 ml. of tetrahydrofuran is poured into 200 ml. of ether saturated with carbon dioxide at C. The reaction mixture is extracted with dilute sodium hydroxide solution, neutralized with dilute acid and concentrated, The residue is taken up in ether, washed with dilute hydrochloride acid, dried and concentrated to give Z-benzyl-S-trifluoromethylbenzoic acid, m.p.

A solution of 19.9 g. of the above acid, in 58 ml. of concentrated sulfuric acid is stirred at room temperature for 3 hours, poured into 700 ml. of water and filtered to give 2- trifluoromethyl-lOanthrone, m.p. l48-150 C.

A mixture of 8.65 g. of 3-methoxypropyl chloride and 1.9 g. of magnesium in 100 ml. of ether is stirred and refluxed for 2 hours. To this mixture at 10 C. is added a suspension of 6.0 g. of 2-trifluromethyl-lO-anthrone in ether. After stirring for 3 hours at 10 C., then 16 hours at room temperature, the reaction mixture is poured into ammonium chloride solution and extracted with ether. The extract is evaporated, taken up in benzene, extracted with base, washed with water. dried and evaporated to give 2-trifluoromethyl-l0-hydroxy-10-( 3- methoxypropyl)-9, lO-dihydroanthracene. The latter 2.0 g., 111 7.5 ml. of 48 percent hydrobromic acid and 14 ml. of glacial acetic acid is refluxed for 6 hours. The reaction mixture is evaporated, taken into ether and chromatographed to give 2- trifluoromethyll 04 3-bromopropyl l-anthracene, m.p. 87-88 C.

The above anthracene 15.0 g.) and 18 g. of dimethylamine in 45 m1. of benzene is heated on the steam bath in a pressure bottle for 6 hours. The reaction mixture is treated with water and extracted with dilute hydrochloric acid. The acid extract is made basic, extracted with ether and the dried ether extract IS evaporated to give Z-trifluoromethyh l 0-( 3 dimethylaminopropyl)-anthracene b.p. -160 C./0.35 mm.

A mixture of 3.8 g. of the above anthracene, 0.6 g. of copper chromite and 15 ml. of Decalin is heated at 200 C. under 4,000 lbs. hydrogen pressure for 3 hours to give upon workup the product 2-trifluoromethyl-l0-(3- dimethylaminopropyl)9,10-dihydroanthracene; hydrochloride salt, m.p. l94.5-196 C.

EXAMPLE 4 To a mixture of 0.72 g. of sodium hydride (56 percent) suspension in mineral oil) nd 3.7 g. of trimethylsulfoxonium iodide in 25 ml. of dimethylsulfoxide is added 5.0 g. of 2- bromo-4-trifluoromethylbenzophenone (prepared as in example 3) in 8 ml. of dimethysulfoxide. The resulting mixture is stirred for 30 minutes at room temperature then heated at 5055 C. for 90 minutes. The reaction mixture is poured into water, extracted with ether, and the extract evaporated to give l-phenyl-1-(-bromo-4-trifluoromethylpheny1)-ethylene oxide, m.p. 77-78 C.

The above oxide 12.7 g.) in 55 ml. of ether is added to 1.0 g. of lithium aluminum hydride in 55 ml. of ether and the mixture is refluxed for 1 hour. Water (2 ml.) is added and the reaction mixture is filtered to give a-phenyl-a-(2-bromo-4- trifluoromethylphenyl)-ethanol. The latter (12.5 g.) is refluxed and stirred with 12.5 g. of red phosphorus and 25 ml. of 57 percent hydroiodic acid for 24 hours. The reaction mixture is filtered to give 2-(a-methylbenzyD-S-trifluoromethylbromobenzene.

A mixture of 2.4 g, of the above bromobenzene, 0.7 g. of cuprous cyanide and 1.5 ml. of dimethylformamide is stirred and refluxed for 4 hours. The reaction mixture is poured into a solution of 3.1 g. of ferric chloride in 4.5 ml. of water and 0.8 m1. of concentrated hydrochloric acid, extracted with chloroform, water-washed, dried and distilled to give 2-(amethylbenzyl)-5-trifluoromethylbenzonitrile.

To the Grignard solution formed with 6.2 g. of 3-methoxypropyl chloride and 1.4 g. of magnesium in 75 ml. of tetrahydrofuran is added 5.0 g. of the above nitrile in 50 ml. of tetrahydrofuran and the mixture is refluxed for 2 hours. The reaction mixture is decomposed with ammonium chloride solution and extracted with ether. The dried ether extract is evaporated to give the methoxypropyl imine (29 g.) which is refluxed for 6 hours in 100 ml. of 48 percent hydrobrornic acid and 200 ml. of acetic acid. The reaction mixture is evaporated, extracted with ether and the dried extract chrmatographed to give 2-trifluoromethyl-9-methyl-10,-( 3- bromopropyl )-anthracene.

' A mixture of 12.0 g. of the above anthracene and 18 g. of dimethylamine in 60 ml. of dry benzene is heated in a pressure bottle on the steam bath for hours. The reaction mixture is treated with water and extracted with diluted hydrochloric acid. The acid extract is made basic, extracted with ether and the dried extract evaporated to give 2-trifluoromethyl-9- methyl-l0-(3-dimethylaminopropyl)-anthracene, b.p. 165-170C./O.l mm.; hydrochloride salt, m.p. 263 C. (dec.).

The above anthracene (2.0 g.) is reduced with 0.34 g. of copper chromite in 4 ml. of Decalin at 200 C. and 4,000 lbs. of hydrogen for 3 hours to give 2-trifluoromethyl-9-methyl-1O 3-dimethylaminopropy1)-9, 1 O-dihydroanthracene; hydrochloride salt, m.p. 179-1 81 C. This is the cis-isomer.

Similarly, reaction of 2-trifluoromethyl-9-methyl-10-( 3- bromopropyl)-anthracene with N-methylpiperazine as described above followed by reduction yields the corresponding 2-trifluoromethyl-9-methyll 0-[ 3-( N'-methyl-N-piperazinyl)-propyl]-9,10-dihydroanthracene EXAMPLE 5 A mixture of 12.0 g. of 2trifluoromethyl-l0-(3- bromopropyl)-anthracene (prepared as in example 3) and 4.9 of N-methylpiperazine in 40 ml. of benzene is heated in a pressure bottle on the steam bath for 12 hours. Water is added to the reaction mixture, made basic and benzene separated which gives Z-trifluoromethyll O-[ 3-N-methyl-N-piperazinyl)-propyl]-anthracene, b.p. 185-189 hydrochloride salt, m.p. 280 C. (dec.).

The above anthracene free base (4.6 g.) in 10 ml. of Decalin and 0.74 g. of copper chromite are heated at 200 C. and 4,000 lbs. hydrogen to give 2-trifluoromethyl-lO-[3-(N- methyl-N-piperazinyl )-propyl ]-9, l O-dihydroanthracene; hydrochloride salt, m.p. 263 C.

Similarly, in the above reaction sequence, reacting an equivalent amount of pyrrolidine or piperidine instead of N- methylpiperazine results in the formation of 2- trifluoromethyll 0[ 3-( N-pyrrolidinyl )-propyl ]-9, l 0- dihydroanthracene and 2-trifluoromethyl-l0-(3-(N-piperidinyl)-propyl]-9, IO-dihydroanthracene, respectively.

C./0.1 mm.;

EXAMPLE 6 Following the general procedures of example 1, a mixture of 12.7 g. of magnesium and 64.0 g. of 3-methoxy-2-methylpropyl chloride in 300 ml. of ether is treated with 31.2 g. of 2- methyl-lO-anthrone in 250 m1. of ether to give 2-methyl-10- hydroxy-10-(3-methoxy-2-methylpropyl)-9,10- dihydroanthracene. The latter is similarly dehydrated and hydrolyzed with 48 percent hydrobrornic acid and the bromo compound reacted with dimethylamine to give 2'methyl-10-( 3 -dimethylamino-2-methylpropyl)-anthracene. Reduction with red phosphorous and 57 percent hydroiodic acid yields the product, 2-methyl- 1 0-( 3-dimethylamino-2methylpropyl )9 ,10- dihydroanthracene.

EXAMPLE 7 Following the procedure outlined in example 3 2- trifluoromethyl-l0-(3-bromopropyl)-anthracene (15.0 g.) is treated with excess aqueous ammonia, methylamine or butylamine to give after reduction the products, 2trifluoromethyl- 1 0-( 3-aminopropyl )-9, l 0- dihydroanthracene, 2-trifluor0methyll 0-( 3- methalaminopropyl)9,10-dihydroanthracene and 2- trifluoromethyl-10-(3-butylaminopropyl)-9,l0-

dihydroanthracene, respectively.

EXAMPLE 8 EXAMPLE 9 A mixture of 10 g. of 2-trifluoromethyI-9-methyl-10-(3- dimethylaminopropyl)-anthracene (prepared as in example 4), 15 g. of red phosphorus and 70 ml. of 57 percent hydroiodic acid solution is refluxed and stirred for 40 minutes. The reaction mixture is poured into water, made basic with sodium hydroxide solution, stirred for 1 hour with solution ether and filtered. The dried filtrate is evaporated in vacuo to give the free base which is a mixture consisting of about percent of the transand 20 percent of the cisisomer of 2- trifluoromethyl-9-methyl-10-( 3-dimethylaminopropyl)-9, 10- dihydroanthracene. Recrystallization of the hydrochloride salt of the mixture from a acetone-ethyl acetate yields the pure trans-isomer hydrochloride, m.p. 200-201C.

EXAMPLE 10 A mixture of 18.5 g. of l-di-p-to1uoyltartaric acid and 16.7 g. of cis-2-trifluoromethyl-9-methyl-10-(3- dimethylaminopropyl)-9,lo-dihydroanthracene (prepared as in example 4 on 100 ml. of boiling methanol and 10 ml. of water yields the l-di-p-toluoyltartrate salt, m.p. 167 C. (foam), [a],, =+3.66. The free base liberated from this salt with ammonium hydroxide and ether is converted to the hydrochloride salt of d-cis-2-trifluoromethyl-9-methyl-10-( 3- dimethylaminopropy1)-9, IO-dihydroanthracene, m.p. 209-210C., [a],, =+9.62 (2 percent ethanol).

The filtrate from the crude l-di-p-toluoyltartrate salt above is treated with ammonium hydroxide and ether to regenerate 13.5 g. of the cis free base. The latter with 15.0 g. of d-di-ptoluoyltartaric acid in 200 ml. of methanol and 20 ml. of water forms the d-di-p-toluoyltartrate salt, [a],, =-2.4 (1 percent ethanol). The liberated free base is converted to the hydrochloride salt of l-cis-2-trifluoromethyl-9-methyl-10-( 3- dimethylaminopropyl )-9, 1 O-dihydroanthracene, mp. 206208C., [a],," =9.6 (2 percent ethanol).

EXAMPLE 1 1 To a solution of 71.8 g. of 2-benzy1-S-trifluoromethylbenzonitrile (prepared from 2-bromo-4-trifluoromethyldiphenylmethane by reaction with cuprous cyanide) in 100 ml. of ether is added gradually 183 ml. of 3M methyl magnesium bromide in ether. The reaction mixture is refluxed with stirring for 6 hours, decomposed with aqueous ammonium chloride, extracted with ether and evaporated. The residue is taken up in 250 ml. each of 48 percent hydrobromic acid solution and acetic acid, refluxed for 18 hours, evaporated and extracted with chloroform. The filtered extract is evaporated, the residue is dissolved in methanol and the solvent removed to give 2-trifluoromethyl-10-methylanthracene, m.p. 98100 C. 1

A mixture of the above prepared anthracene (33.2 g.) and 34.2 g. of N-bromosuccinimide in 300 ml. of carbon tetrachloride, catalyzed by 0.34 g. of benzoyl peroxide, is refluxed and stirred for 2 hours. The hot reaction mixture is filtered and cooled to precipitate 2-trifluoromethyl-10- bromomethylanthracene.

To 5.2 g. of 57 percent sodium hydride in 100 ml. of dimethysulfoxide at 50 C. is added slowly a solution of 19.8 g. of diethylmalonate in dimethylsulfoxide and the mixture is heated at 75 C. for 45 minutes. A slurry of 36.5 g. of 2- trifluoromethyl-lO-bromoethylanthracene in dimethylsulfoxide is added and the resulting mixture is heated at 75 C. for 1 hour. The reaction mixture is quenched with water and extracted with ether to give diethyl (3-trifluoromethyl-10- anthracenyl)-methylmalonate. The latter (50.7 g.) is hydrolyzed with 41 g. of potassium hydroxide in 200 ml. of 60 percent ethanol to the free malonic acid which is heated at 185200C. to obtain 2'-trifluoromethylanthracene-10- propionic acid.

A mixture of 32.7 g. of the above prepared propionic acid and 48 g. of red phosphorus in 160 ml. of 57 percent hydroiodic acid and 75 ml. of acetic acid is refluxed and stirred for 3 hours. The reaction mixture is diluted with water, extracted with chlorofonn, washed with water and evaporated to yield 2-trifluoromethyl-9, 1 O-dihydroanthracene- 1 propionic acid, m.p. 153-155 C.

A solution of 8.0 g. of 2-trifluoromethyl-9,l0- dihydroanthracene-lO-propionic acid and 3.0 g. of d-aphenethylamine in 45 ml. of ethanol is clouded with 50 ml. of water while boiling to give the d-a-phenethylamine salt, m.p. 179-18lC., [a],,"' 3.2 (1 percent ethanol). This salt is acidified with hydrochloric acid, extracted with ether and the dried extract evaporated to give l-2-trifluoromethyl-9,l0- dihydroanthracene-IO-propionic acid. The latter is refluxed with ml. of thionyl chloride for 2 hours and the resulting acid chloride dissolved in 20 ml. of benzene is saturated with dimethylamine to yield the dimethylamide. The amide (2.2 g.)

in ether is added to 1.1 g. of lithium aluminum hydride in ether, refluxed for 1 hour and worked up to give d-2- trifluoromethyll 0-( 3-dimethylaminopropyl )-9, l 0- dihydroanthracene; hydrochloride salt, mp. 201-202 C., [a] =+4.92 1 percent ethanol).

The filtrate from the crude d-a-phenethylamine salt above is evaporated, acidified and extracted with ether to regenerate 2-trifluoromethyl-9,IO-dihydroanthracene-10-propionic acid. The latter (6.2 g.) and 2.4 g. of l-a-phenethylamine dissolved in 30 ml. of ethanol is clouded while boiling with 50 ml. of water to give the l-a-phenethylamine salt, m.p. 177-l79 C., [a],, =+3.46. This salt is acidified to liberate d-2- trifluoromethyl-9, 1 O-dihydroanthracenel O-propionic acid which is treated as above with thionyl chloride, the acid chloride reacted with dimethylamine and the amide reduced with lithium aluminum hydride to yield l-2-trifluoromethyl- 1 0- (3-dimethylaminopropyl )-9, 1 O-dihydroanthracene; hydrochloride salt, m.p. 200-202 C., [a],,**=5.73 (l percent ethanol).

EXAMPLE 12 Following the general procedure of example 3, 18.2 g. of 2- bromo-4-methylthiobenzonitrile (obtained from 4- methylthiobenzonitrile) and 29 ml. of 3M phenylmagnesium bromide in ether solution are reacted to give 2-bromo-4- methylthiobenzophenone. A mixture of the latter and red phosphorus in 57 percent hydroiodic acid is refluxed and stirred under nitrogen for 24 hours to 2-bromo-4- methylthiodiphenylmethane. The Grignard reagent prepared from this diphenylmethane in tetrahydrofuran is poured into ether saturated with carbon dioxide at C. Workup yields 2-benzy1-5-methylthiobenzoic acid. A solution of the acid in concentrated sulfuric acid is stirred. at room temperature to give the ring-closed product, 2-methylthio-10-anthrone.

To the Grignard reagent prepared from 8.65 g. of 3-methoxypropyl chloride in ether is added a suspension of 5.5 g. of 2methylthio-l0-anthrone in ether. After stirring for 3 hours at 10 C. and 18 hours at room temperature, the reaction mixture is decomposed and worked up to give 2-methylthio-l0- hydroxy-10(3-methoxypropyl)-9,l0dihydroanthracene. The latter is refluxed in 48 percent hydrobromic acid and glacial acetic acid to give 2-methylthio-10-( 3-bromopropyl)- anthracene.

The above anthracene 13.7 g.) and 18 g. of dimethylamine in benzene is heated on the steam bath in a pressure bottle for 6 hours to give upon workup 2-methylthio-10-( 3- dimethylaminopropyl)-anthracene which is hydrogenated in the presence of copper chromite to yield 2-methylthio-10-(3- dimethylaminopropyl)-9,10-dihydroanthracene.

Similarly, by employing 2-bromo-4-methylsulfonylbenzonitrile (obtained from the 4-methylthio derivative by oxidation with chromic anhydride in sulfuric acid) in the above described reaction sequence there is obtained as a final product, 2-methylsulfonyl-10-( 3-dimethylaminopropyl)-9, l0- dihydroanthracene.

EXAMPLE 1 3 Following the general procedure of example 3, 16.8 g. of 3- bromo-4-cyano-N,N-dimethylbenzenesulfonamide (obtained from 4-cyano-N,N-dimethylbenzenesulfonamide in ether is reacted with 29 m1. of 3M phenylmagnesium bromide in ether and the mixture worked up to give 2-bromo-4N,N-dimethylsulfamy)-benzophenone which is reduced with red phosphorus and hydroiodic acid to the corresponding diphenylmethane. The Grignard reagent prepared from this diphenylmethane is reacted with carbon dioxide with cooling to give 2-benzyl-5-(N,N-dimethylsulfamyl)-benzoic acid. Ring closure is effected via concentrated sulfuric acid to yield 2-( N,N dimethylsulfamyl l0-anthrone The Grignard reagent prepared from 8.65 g. of 3-methoxypropyl chloride is reacted with 5.0 g. of the above-prepared anthrone to give 2-( N,N-dimethylsulfamyl)-10-hydroxy-10- hours (3-methoxypropyl)-9,lO-dihydroanthracene. The latter is refluxed in 48 percent hydrobromic acid and glacial acetic acid to give 2-(N,N-dimethylsulfamyl)-l0-(3-bromopropyl)- anthracene.

The above anthracene 12.6 g.) and 18 g. of dimethylamine in benzene is heated on the steam bath in a pressure bottle for 6 hours to give upon workup 2-(N,N-dimethylsulfamyl)-10-(3 -dimethylaminopropyl)-anthracene which is hydrogenated in the presence of copper chromite to yield 2-(N.N-dimethysu1famyl)-l0-(3-dimethylaminopropyl)-9,10-dihydroanthracene.

EXAMPLE 14 To a solution of 32.9 g. of 2-br0mo-4-trifluoromethylbenzophenone in 400 ml. of ether is added one equivalent of ethylmagnesium bromide in ether and the resulting mixture is refluxed for 4 hours. Treatment with aqueous acid gives aphenyl-a-( 2-bromo-4-trifluoromethylphenyl )-propanol. The latter (13.0 g.) is refluxed and stirred with 12.5 g. of red phosphorus and 25 ml. of 57 percent hydroiodic acid for 24 to yield 2-( a-ethylbenzyl )-5 -trifluoromethylbromobenzene.

A mixture of 2.5 g. of the above bromobenzene, 0.7 g. of cuprous cyanide and 1.5 ml. of dimethylformamide is stirred and refluxed for 4 hours. The reaction mixture is poured into a solution of 3.1 g. of feric chloride in 4.5 ml. of water and 0.8 ml. of concentrated hydrochloric acid, extracted with chloroform, water-washed, dried and distilled to give 2-(aethylbenzyl)S-trifluoromethylbenzonitrile.

To the Grignard reagent formed with 6.2 g. of 3-methoxypropyl chloride in 75 ml. of tetrahydrofuran is added 5.2 g. of the above nitrile and the mixture is refluxed for 2 hours. The decomposed reaction mixture yields the methoxypropyl imine which is refluxed for 6 hours in 100 ml. of 48 percent hydrobromic acid and 200 ml. of acetic acid. The reaction mixture is evaporated, extracted with ether and the dried extract chromatographed to give 2-trifluoromethyl-9-ethyl-l0- (3-bromopropyl)-anthracene.

A mixture of 12.5 g. of the above anthracene and 18 g. of dimethylamine in 60 ml. of dry benzene is heated in a pressure bottle on a steam bath for 5 hours. The reaction mixture is heated with water and extracted with dilute hydrochloric acid. The acid extract is made basic and further worked up to give 2-trifluoromethyl-9-ethyl-10-(3-dimethylaminopropyl)- anthracene. The latter (2.8 g.) is reduced with 0.34 g. of copper chromite in 4 ml. of Decalin at 200 C. and 4,000 lbs. of hydrogen to yield Z-trifluoromethyl-Q-ethyl-10-(3- dimethylaminopropyl )-9, l O-dihydroanthracene.

Similarly by commencing the above sequence of reaction employing phenylmagnesium bromide instead of ethylmagnesium bromide there is obtained the corresponding 2- trifluoromethyl-9-phenyll 0-( 3-dimethylaminopropyl )-9, 1 0- dihydroanthracene.

EXAMPLE To a suspension of 2.1 g. of 57 percent sodium hydride in 45 ml. of dimethylsulfoxide in added gradually, with stirring, 7.5 g. of 9-methyl-9,IO-dihydroanthracene and the mixture heated at 70 C. for 2 hours. A solution of 7.5 g. of 3- dimethylaminopropyl chloride in 30 ml. of dimethylsulfoxide is added and heating is continued for 3 hours. The reaction mixture is quenched with water, extracted with ether and the ether extracted with dilute hydrochloric acid. The acid extract is made basic to give the liberated base. 9-methyl-l0-(3- dimethylaminopropyl )9 1 Odihydroanthracene, hydrochloride salt, m.p 213-216 C EXAMPLE 16 To a solution of 24.8 g. of 9-methyI-9,l0- dihydroanthracene in 300 ml of ether is added over 15 minutes 96 ml. of 15 percent lithium in hexane and the resulting mixture is stirred at room temperature for 2 hours. After adding 24.6 g. of B-dimethylaminopropyl chloride, the mixture is stirred and refluxed for 3 hours and allowed to stand overnight The reaction mixture is extracted with dilute hydrochloric acid, made basic, extracted with ether and distilled to give the free base, b.p. 160 C./0.5 mm. The latter is fractionated and the first fraction collected at b.p. -139" C./0.15 mm. is cis-9-methyl-10-(3-dimethylaminopropyl)- 9,10-dihydroanthracene; hydrochloride salt, m.p. 2 17-2 1 8 C The second fraction obtained from above (4.5 g.) is heated about 1 hour at 70 C. with 0.81 g. of 57 percent sodium hydride in 40 ml. of dimethylsulfoxide. The reaction mixture is quenched in water, extracted with ether, dried and evaporated. The residual free base is converted to a hexamate salt in acetone and recrystallized from acetonitrile to give trans-9-methyl-l0-(3-dimethylaminopropyl)-9,10- dihydroanthracene hexamate, m.p. 169-17 1 C.

What we claim is:

1. A chemical compound of the structural formula:

in which:

R is hydrogen, lower alkyl or phenyl;

Y is halogen having an atomic weight of less than 80, lower alkyl, trifluoromethyl, lower alkylthio or lower alkylsulfonyl;

A is an alkylene chain of two to four carbon atoms; and

Z is amino, mono-loweralkylamino or di-loweralkyl-amino,

each of said lower alkyl or alkoxy moieties having from one to four carbon atoms, or its nontoxic, pharmaceutically acceptable, acid addition salt.

2. A chemical compound in accordance with claim 1 in which R is hydrogen, methyl, ethyl, or phenyl; Y is the 2-position; A is propylene and Z is dimethylamino.

3. A chemical compound in accordance with claim 2 in which Y is chlorine, methyl, trifluoromethyl, methylthio or methysulfonyl.

4. A chemical compound in accordancewith claim 1 in which R is hydrogen or methyl; Y is trifluoromethyl and Z is monomethylamino or dimethylamino.

5. A chemical compound in accordance with claim 4 in which Y is 2-trifluoromethyl.

6. A chemical compound in accordance with claim 5 in which A is propylene.

7. A chemical compound in accordance with claim 6 in which Z is dimethylamino.

8. A chemical compound in accordance with claim 7 in which R is hydrogen, being the compound 10-(3- dimethylaminopropyl )-2-trifluoromethyl-9, l O- dihydroanthracene.

9. The d-isomer of the compound in accordance with claim 8.

10. The l-isomer of the compound in accordance with claim 8.

11 A chemical compound in accordance with claim 7 in which R is methyl, being the compound 9-methyl-10-( 3- dimethylaminopropyl)-2-trifluoromethyl-9, 10- dihydroanthracene.

12. The cis-isomer of the compound in accordance with claim ll 13. The d-isomer of the compound in accordance with claim l2.

14 The l-isomer of the compound in accordance with claim 12.

15 The trans-isomer of the compound in accordance with claim 11 16. A chemical compound of the structural formula:

in which:

R is lower alkyl or phenyl;

A is an alkylene chain of two to four carbon atoms; and

Z is amino, mono-loweralkylamino or di-loweralkylamino;

each of said lower alkyl of alkoxy moieties having from one to four carbon atoms, or its nontoxic, pharmaceutically acceptable, acid addition salt.

21. A chemical compound in accordance with claim 20 in which R, is lower alkyl, A is propylene and Z is dimethylamino.

22. A chemical compound in accordance with claim 21 in which R, is methyl, being the compound 9-methyl-lO-( 3- dimethylaminopropyl )-9, 1 O-dihydroanthracene.

23. The cis-isomer of the compound in accordance with claim 22.

24. The trans-isomer of the compound in accordance with claim 22.

mg UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3 ,622 Dated November 23 1971 Inventor) Paul N. Craig and Charles L. Zirlcle.

It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Column 3, lines 35-45, reaction sequence indicated as: CH CH l 3 i 3 Y l U CH O-A-MgX Y I CN k -.1 should read: 3

V A Y Column 4, lines 37-46, under the structural formulas should appear (from left to right) CIS TRANS Column 5, lines 35-45, the structural formula under D;

*zggg UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Pa 3 ,622,630 Dated November 23 1971 Inventor) Paul N. Craig and Charles L. Zirkle It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Column 5, line +1, delete the second occurrence of:

Signed and sealed this 20th day of June 1972.

(SEAL) fittest:

JDNARD ILFLETCHEH, JR. ROBERT GOTTSCHALK Attesting Officer Commissioner of Patents

Claims (23)

1. 2. A chemical compound in accordance with claim 1 in which R is hydrogen, methyl, ethyl, or phenyl; Y is the 2-position; A is propylene and Z is dimethylamino.
2. 3. A chemical compound in accordance with claim 2 in which Y is chlorine, methyl, trifluoromethyl, methylthio or methysulfonyl.
3. 4. A chemical compound in accordance with claim 1 in which R is hydrogen or methyl; Y is trifluoromethyl and Z is monomethylamino or dimethylamino.
4. 5. A chemical compound in accordance with claim 4 in which Y is 2-trifluoromethyl.
5. 6. A chemical compound in accordance with claim 5 in which A is propylene.
6. 7. A chemical compound in accordance with claim 6 in which Z is dimethylamino.
7. 8. A chemical compound in accordance with claim 7 in which R is hydrogen, being the compound 10-(3-dimethylaminopropyl)-2-trifluoromethyl-9,10-dihydroanthracene.
8. 9. The d-isomer of the compound in accordance with claim 8.
9. 10. The l-isomer of the compound in accordance with claim 8.
10. 11. A chemical compound in accordance with claim 7 in which R is methyl, being the compound 9-methyl-10-(3-dimethylaminopropyl)-2-trifluoromethyl-9,10 -dihydroanthracene.
11. 12. The cis-isomer of the compound in accordance with claim 11.
12. 13. The d-isomer of the compound in accordance with claim 12.
13. 14. The l-isomer of the compound in accordance with claim 12.
14. 15. The trans-isomer of the compound in accordance with claim 11.
15. 16. A chemical compound of the structural formula:
16. 17. A chemical compound in accordance with claim 16 in which R is hydrogen and Y is 2-trifluoromethyl.
17. 18. A chemical compound in accordance with claim 17 in which A is propylene.
18. 19. A chemical compound in accordance with claim 18 in which Z is dimethylamino.
19. 20. A chemical compound of the structural formula:
20. 21. A chemical compound in accordance with claim 20 in which R2 is lower alkyl, A is propylene and Z is dimethylamino.
21. 22. A chemical compound in accordance with claim 21 in which R2 is methyl, being the compound 9-methyl-10-(3-dimethylaminopropyl)-9,10-dihydroanthracene.
22. 23. The cis-isomer of the compound in accordance with claim 22.
23. 24. The trans-isomer of the compound in accordance with claim 22.