IL46087A - 1,2,3,5-tetrahydro-5,9b-(1',2')-benzeno-9bh-benz(e)isoindoles - Google Patents

Description

ϊ>9,5«τπ*ϊΝηΒ0~5,3,2,1 &*>VTintif-ntfe7 1,2,3,5-ietrahydro«5,9¾-/ϊ' »2l7-¾enssno«-9¾H-bens/e7±soindoles 0* 43923 46087/2 This invention relates to novel 9,12-bridged ethenoanthracenes containing N in the bridging group, and to methods of making the above compounds.

More specifically the invention relates to 1,2,3, 5-tetrahydro-5 , 9b [1 ' , 21 ] -benzeno-9bH-benz [e] isoindoles and to their preparation.

Unbridged 9 , 10-ethenoanthracenes are well known in the art, and certain 9 ,12-bridged (ethenoanthracenes have been described (Meek et al., J. Am. Chem. Soc. , 761 (1952); ibid, 78, 5M13 (1956); ibid, 8_2 , 2566 (1960); Alder and Heim-bach, Chem. Ber. , 8 , 1312 (1953); British Patent 1,266,890). A low yield of a 9,12-bridged ethenoanthracene, was obtained by an intramolecular Diels-Alder reaction (Meek and Dann, J. Org. Chem., 21, 968 (1956)).

The compounds of this invention have the following structure : where X is selected from one of the following groups -CH=NCH2-; -CO (R3) CH2~; and -CH2 (R3 ) CH2- in which R3 is hydrogen, alkyl of up to 12 carbon atoms , lower alkenyl attached to N by a saturated carbon atom, cycloalkyl of 3-9 carbon atoms, alkylmethyl of 4-10 carbons, cycloalkenylmethyl , adamantylmethyl , benzyl, or β-phenylethyl .

The preferred X linkages are -CH2 - NR3 - CH2 - 3 where R is H, alkyl of up to 12 carbon atoms (most preferably a lower alkyl,) cycloalkylmethyl of 4-10 carbons atoms or benzyl.

R1 and R2 are the same or different and are each hydrogen, lower alkyl or halogen., with the proviso that at least 1 2 is one of R and R be hydrogen. Preferably, one of R1 and R2 is chlorine and the remaining R is hydrogen.

The term "lower" as used herein means 1-4 carbon atoms .

Some of the compounds of this invention, e.g. 'the amines, when heated with an acid catalyst, undergo a rearrange- i ment to dihydromethanodibenzocycloheptapyrroles which, upon reduction, yield tetrahydro derivatives as described in Belgian Patent Specification 826,391. The amides or lactams of this invention may be rearranged by the action of bromine in a solvent, e.g. methylene chloride, to give dibromodihydrometh- anodibenzocycloheptapyrrol-ones . The bromine is then removed and the lactam reduced to give the above-merttioned tetrahydro derivatives. Many of the latter compounds are tranquilizing agents in warm-blooded animals.

All the compounds of the invention are useful as inhibitors of free radical vinyl ^polymerization.

The compounds of formula I , are numbered as follows: I.

These compounds are prepared by internal Diels-Alder reaction of the corresponding alkynyl-substituted anthracenes^as shown by equation (1) : This process can be carried out by heating the by itself alkynylanthracene , either neat or in a suitable inert solvent, preferably an aromatic hydrocarbon, at a temperature of 80- 250°C depending upon the particular atoms in the X chain and the values of the substituents R. Reaction is carried out for a sufficient time to effect the cyclization; preferably from 1-48 hours.

The following reactions can be used to make the required alkynyl anthracene compounds used as starting materials The 9-anthraldehyde compound is reacted with a suitable amine at 25° to 150°C in an alcohol solvent to form an imine. The imine is then reduced with a metal hydride reducing agent such as sodium borohydride or sodium cyano borohydride in an alcohol such as methanol, ethanol, or isopropanol, which can be the same solvent that is employed to form the imine, at a temperature between 0°C and 100°C.

The resultant secondary amine is then condensed presence of an inorganic base such as an aqueous solution of an alkali metal carbonate or a organic base which does not react substantially with propargyl bromide, e.g., certain hindered amines including diisopropylethylamine, at a temperature of 0 to 100eC, preferably ambient temperatures.

The alky3¾yl substituted anthracenes are then cyclized to compounds of Formula I as described hereinabove.

A procedure to make N-containihg compounds of p. formula I where R^ is H is to react propargylamine with a 9-anthraldehyde in alcohol at 25-150°C to form the imine.

The imine can then be cyclized as described above and thereafter reduced with sodium cyanoborohydride in alcoholic solution at 0 to 100°C. Alternatively the reduction can be accomplished prior to cyclization.

The above procedure yields compounds having the formula whieh can be alkylated or acylated to introduce various R substituents at the nitrogen atom. Acyl substituents can then be reduced to the corresponding amine.

Yet another method is to react a 9-halomethyl, preferably chloromethyl anthracene compound with R5NH2 in an inert sol vent at ambient temperatures to 150eC to form a secondary amine substituted anthracene which is then reacted with a propargyl halide, preferably bromide as described above.

Other methods can be employed to make various EMBODIMENTS OF THE INVENTION The following examples illustrate specific embodiments of this invention, but they should not, however, be construed as fully delineating the scope of the discovery.

EXAMPLE 1 3 5-Dihydro-5,9b-o-benzenobenz [e]isoindol-1(2H) -one A mixture of 18.85 6 of 9-anthrpic acid and 60 ml cof -thionyl chloride, is heated under reflux for 1 hour. The excess thionyl chloride is removed under vacuum (30 mm; 9 ° bath temperature); 0 ml of toluene is added and the mixture is concentrated again. This operation is repeated once more to give 20.6 g of 9-anthroyl chloride as a very moisture- sensitive, yellow solid.

A solution of 13.68 g of 9-anthroyl chloride in 30 ml of tetrahydrofuran is added at 10-15° to a solution of 10 g of propargylamine in 60 ml of tetrahydrofuran. After stirring at room temperature for 4 hours, the solvent is removed and the residue is stirred with methylene chloride and 5$ aqueous sodium bicarbonate solution. The methylene chloride layer is dried and concentrated to give 14. g of crude N-propargyl-9-anthramide as a solid. An analytical sample (ethanol) had a melting point of 201-202°; H nmr spectrum: τ 1.5-2.8 (ra, 9) ; 3.7 (broad, 1); 5.7 (d of d, 2) and 7.7 (t; 2,5 Hz. 1).

Anal. Calcd for Ci aHi3N0: C, 83.37; H, .0 ; N, 5. 0 Found: C, 83.50; H, 5.08, N, 5.29.

A mixture of 10 g of crude N-propargyl-9-anthramide and 200 ml of p_-xylene is heated under reflux overnight. The solvent is removed and the residue is sublimed at 200-210° bath temperature (0.5 micron). Crystallization of the sublimate from 110 ml of acetonitrile gives 4.7 g of 3 , 5-dihydro-5, 9k-o-benzenobenzre]isoindol-l(2H)-one, rap, 264-265° , unchanged on recrystallization; nmr spectrum: τ 2.3-3.3 (m, 10) 4.8 (d, J = 6 Hz, 1) and 5.9 (d, J = 2 Hz, 2).

Anal. Calcd for CieH13N0: C, 83.37; H, 5.0 N, 5.40 Found: C, 83.19; H, 5.11 ; N, 5.40.

EXAMPLE 2 2-Methyl-3 5-dlhydro-5>9b-o-bcn^cnobcnzf Gllsolndol-l(2H)-onc Following the procedure given in Example 1, but using N-methylpropargylamine in place of propargylamine, there is obtained, in turn: N-raethyl-N-propargyl-9-anthramide as an oil; H nmr spectrum: τ 1.7-2.9 (ω, 9) ; 5.4 (d, 2.5 Hz, 1.3 ) ; 6.4 (d, 2.5 Hz, 0.7 ) ; 6.7 ( B, 0.9) ; 7.4 (s, 2.1 ) ; 7.7 (t, 2.5 Hz, 0.7) and 8.0 (t, 0.3) . The spectrum shows the presence of two rotamers. 2-Methyl-3, 5-dlhydro-5,9b-o-benzenobenz[e]isoindol- 1(2Η)-οηβ, πρ, 250-255° ; nmr spectrum: τ 2.3-3.3 (τη39)> 4.8 (d, J = 6 Kz, 1) ; .9 (d, J - 2 Kz, 2 ) and 6.9 (s, 3 ) .

Anal. Calcd for C19Hl5N0: C, 83.4 ; H, 5.53; N, 5.13 Found: C, 83.84; H, 5.66; N, 5.10.

EXAMPLE 3 3, -Dihydro- , 9b-o-benzenobenz Γ e]isoindole A mixture of 16.7 g of 9-anthraldehyde, 5 g of pro- pargylamine and 100 ml of ethanol is heated under reflux for 1 hour. The solvent is removed and the residue is crystallized from 100 ml of acetonitrilc to give 16.1 g ( 82#) of N-propargyl-9-anthracenemethylenimine; mp, 143-144°; nmr spectrum: τ 0.2 (t, 2 Hz, 1); 1.7-3.0 (in, 9); 5.1 (t, 2 Hz, 2) and 7.3 (t, 2 Hz, 1).

Anal. Calcd for C10H13N: C, 88.86; H, 5.39; N, 5. 6 Found: C, 88.83; H, 5.56; N, 5.87.

A mixture of 19.4 g of crude N-propargyl-9-anthra- cenemethylenimine and 200 ml of. p_-xylene is heated under reflux for 3 hours. On cooling, 14.6 g of , 5-dihydro-5,9b-o- benzenobenz[e]isoindole; mp, 212-214°, precipitates. Another 1.4 g of product is obtained by removing the solvent from the mother liquor and crystallizing the residue from 50 ml of acetonitrile; war spectrum: τ 1.1 (m, 1); 2.5-3.5 (m, 9); 4.8 (d, J = 6 Hz, 1) and 5.4 (t, J = 2 Hz, 2).

Anal. Calca for CieH13N: C, 88.86; H, 5.39; N, 5.76 Found: C, 89.10; H, 5-58; N, 5.66. 3,5-Dihydro-5,9b-o-benzenobenz[e]isoindole may also be prepared directly by heating 9-anthraldehyde with propar- gylamins in p_-xylene.

EXAMPLE 4 1*2,315-Tetrahydro-5,9 -o-benzenobenz f e]isoindole To a slurry of 10.19 g of 3,5rdihydro-5,9b-o-ben-" senobenzfe]isoindole in 50 of methanol and 10 ml of acetic acid is added slowly, with cooling, .70 g of sodium cyanoborohydride. The mixture is stirred at room temperature overnight, the excess hydride is destroyed with concentrated hydrochloric acid (ice bath), and the mixture is made basic and extracted with methylene chloride. Removal of the solvent from the dried extract gives 10.49 g of 1, 2,3, S-tetra-hydro-S^b-benzenobenzfeJisoindole as an oil that slowly solidifies; nmr spectrum: τ 2.6-3.7 (m, 9); 4.9 (d, 6 Hz, 1); 6.0 (s, 2); 6.5 (d, 2 Hz, 2) and 7.5 (s, 1). The hydrochloride melted at 273° (dec) after crystallization from isopropyl alcohol.

EXAMPLE 5 2-Methyl-l ,2,3,5-tetrahydro-5 , 9b-o-benzenobenz[eKsoindole A mixture of 8.19 S o 3,5-dihydro-5, 9b-o-benzeno-benzfe]isoindole, 25 ml of formic acid and 25 ml of aqueous formaldehyde solution is heated under reflux for 3 hours.

Concentrated hydrochloric acid (10 ml) is added, and the vol-atiles are removed. The residue is stirred with aqueous sodium hydroxide solution and methylene chloride. Removal of the solvent from the dried methylene chloride extracts and crystallization of the residue from acetonitrile Rives , in two crops, 5.04 g ( 8 ) of 2-methyl-l,2,3,5-tetrahydro-5,9b-o-benzenobenz[e]isoindole, mp 196-197°; nmr spectrum: τ 2.4-3.1 (ra, 8); 3.3 (d of t, J = 6/2 Hz, 1); 4.8 (d, 6 Hz, 1); 6.1 (s, 2)j 6.6 (d, 2 Hz, 2) and 7.3 (s, 3).

Anal. Calcd for Cl9Hl7N: C, 87.995 H, 6.6lj N, . 0 Pound: C, 88.05; H, 6.9I5 N, 5.32.

The N-methyl compound of this example is also obtained by reaction of l,2,3,5-te"trahydro-5,9b-o-benzenobenz-fe]isoindole with formaldehyde and formic acid under similar reaction conditions.

EXAMPLE 6 2-Cyclopentylmethyl-l ,2 , 3 , 5-tetrahydro-5 ,9b-o-benzenobenz- [e ]isoindole A mixture of 43.5 g of 9-anthraldehyde , 20.97 g of cyclopentylmethyl amine and 150 ml of ethanol is heated under reflux for 1.5 hours. The hot solution of N-cyclopentylmethyl- 9-anthracenemethyleneimine so obtained is allowed to cool to 60°, and 8.2 g of sodium borohydride is added in small portions, with stirring, while the temperature is maintained at 55-60°. The mixture is then stirred for another 1.5 hours, concentrated hydrochloric acid (35 ml) is added with cooling, and stirring is continued for 0.5 hour. The mixture is then made basic and extracted with methylene chloride. Removal of the solvent from the dried extracts gives 59.1 g of N-cyclopentylmethyl-9- anthracenemethylamine as an oil; nmr spectrum: τ 1.8-3.1 (m, 9); 5.6 (s, 2); 7.5 (d, 7Hz , 2) and 7.8-9.3 (m, 10).

A mixture of 63.5 g of N-cyclopentylmethyl-9-anthracenemethylamine , 50 g of propargyl bromide, 200 ml of methylene chloride and 200 ml of 10% aqueous potassium carbonate solution is stirred vigorously under nitrogen for two hours. The layers are separated and the aqueous layer is extracted once with methylene chloride . Removal of the solvent from the dried extract gives 63.5 g of N-cyclopentylmethyl-N-propargyl-9-anthracenemethylamine as an oil; nmr spectrum: τ 2.3-3.0 (m, 9); 5.5 (s, 2); 6.8 (d, 2.5Hz, 2); 7.5 (m, 2); 7.7 (t, 2.5Hz, 1) and 7.5-9.2 (m, 9). This product is cyclized by heating under reflux in 200 ml toluene for 1.25 hours.

Removal of the solvent and crystallization of the residue from 150 ml of isopropyl alcohol gives 44.4 g of 2-cyclopentylmethyl 1,2,3 ,5-tetrahydro-5 ,9b-o-benzenobenz[e Ksoindole identical by infrared and nmr spectroscopy with the sample prepared by acylation of 1,2 ,3 ,5-tetrahydro-5 ,9b-o-benzenobenz[e]isoindole with cyclopentanecarbonyl chloride followed by reduction.

Following this same procedure, but replacing cyclo-pentylmethylamine with the appropriate amine and substituted 9-anthraldehyde , the following 2-substituted-l ,2 ,3 ,5-tetrahydro 5 ,9b-o-benzenobenz[e]isoindoles are prepared: 2-Cyclopropyl-l ,2 ,3 ,5-tetrahydro-5 ,9b-o-benzenobenz-[eKsoindole , m.p. 109-110°; Anal. Calcd. for C2_Hi9N; C, 88.38; H, 6.71; N, 4.91. Found: C, 88.21; H, 6.68; N, 5.06. 2-Cyclohexyl-l ,2 ,3 , 5-tetrahydro-5 ,9b-o-benzenobenz-[e]isoindole , m.p. 152-154°; Anal. Calcd. for C2HH25 : C, 88.03; H, 7.70; N, 4.28; Found: C, 87.82; H, 7.77; N, 4.35. 2-Benzyl-l ,2,3 ,5-tetrahydro-5 ,9b-o-benzenobenz[e]-isoindole , identical by nmr spectroscopy with the sample pre- pared by benzoylation of 1 , 2 , 3 , 5-tetrahydro-5 , 9b-o-benz*no-benz[e]isoindole followed by reduction. 8-Chloro-2-cyclohexylmethyl-l ,2 , 3 , 5-tetrahydr-o-5 ,9b-o-benzenobenzte]isoindole ; m.p. 144-1M60; Anal. Calcd. for C25H26C1N: C, 79.87; H, 6.97; N , 3.73. Found: C, 79.74; H, 7.09; N, 3.66.

Folowing the procedure of Example 6, but replacing cyclopentylmethylamine with allylamine, 2-allyl-l , 2 , 3 , 5-tetra-hydro-5,9b-o-benzenobenz [ej isoindole was prepared. It showed the nmr spectral pattern characteristic of the 1,2 , 3, 5-tetra-hydro-5,9b-o-benzobenz le] isoindole system with the following additional nmr peaks derived from the 2-allyl substituent: τ, 3.7-4.3 (m, 1); 4.5-5.0 (m,2); 6.7 (d,2) .

EXAMPLE 7 2-Cyclopropylmethyl-l ,2 ,3 ,5-tetrahydro-5 , benzCe Hsoindole To a slurry οΓ 3.75 6 of 1, 2,3, 5-tctrnhydro-5, 9b-o-ben2cnobcnz[c]isolndolo and 3 g of magnesium oxide in 20 rnl^ of anhydrous tetrahydrofuran is added clov/ly a solution of 2.4 g of cyclopropanecarbonyl chloride in 5 ml of tetrahydrofuran. After stirring at room temperature for 5 hours, the mixture is filtered and the filtrate is concentrated to dryness. The residue is taken up in methylene chloride, washed with sodium bicarbonate solution, and dried. Removal of the solvent gives 4.07 g of crude 2-cyclopropylcarbonyl-l,2,3,5-tetrahydro-5, 9b-o-benzenobenz[e]isoindole which is used in the next step without further purification. A sample crystallized twice from isopropyl alcohol had a mp 171-173°. Anal. Calcd for C22H19 0: C, 84. 1; H, 6.11; N, . 7 Found: C, 84.41; H, 6.31; N, 4.88.

A mixture of .87 g of crude 2-cyclo opylcarbonyl-1,2 ,3 ,5-tetrahydro-5 ,9b-o-benzenobenz[e]isoindole , 4.83 g of lithitun aluminum hydride and 100 ml of tetrahydrofuran is heated under reflux for 2 hours. The cooled mixture is treated successively with 4.8 ml of water, 4.8 ml of 15 sodium hydroxide solution, and l4.4 ml of water. Concentration of the filtered mixture gives 9. 9 g of crude 2-cyclo-propylmethyl-1, 2,3, 5-tetrahydro-5, 9b-o-benzenobenz[e]isoindol which after one crystallisation from isopropyl alcohol melted at 109-110°. NMR spectrum: τ 2.5-3.5 (m, 9); 4.8 (d, 6 Hz, 1); 6.1 (s, 2); 6.5 (d, 2 Hz, 2); 7.3 (d, 6 Hz, 2) and 8.7-9.8 (m, 5).

Anal. Calcd for C22H2iN: C, 88.25; H, 7.07; N, 4*68 Found: C, 87.87; H, 7-35; N, 4.70.

- - Following the procedure of Example 7 , but replacing cyclopropanecarbonyl chloride with the appropriate substituted carbonyl chloride, the following 2-substituted 1 ,2 , 3 ,5-tetra- hydro-5 ,9b-o-benzenobenz[e]isoindole system: τ 2.6-3.2 (m,8); 3.4-3.5 (d/t, 6/2 Hz, 1); U.6-5.0 (d, 6Hz, 1); 6.0-6.3 (s, 2) and 6.6-6.8 (d, 2Hz, 2) with minor variations of the chemical shifts depending upon the 2-substituent . The additional signals derived from the 2-substituent are listed separately with each compound . 2-Ethyl-l, 2,3 , 5-tetrahydro-5,9b-o_-benzenobenz[ e] isoindole; nmr spectrum: τ 7-3 (q, 7Hz, 2); 8.7 (t, 7Hz, 5). 2-Isobuty1-1, 2,3 , 5-tetrahydro ~5>9b-o-benzenobenz[ e] iso indole; nmr spectrum: τ 7.6 (d, 7Hz, 2); 7.7-8.5 (m, 1); 9-0 (d, 7Kz, 6). 2-Neopenty1-1,2.3; 5"tetΙ-Ώhydro ~ ,9 -o-be zenoben f e] isoindole; nmr spectrum: τ 7.5 (s, 2); 9.0 (s, 9). 2-CyclobutyImsthy1-1 , 2 , 3 , 5~ etrahydro ~5> b-o_-benzenobenzf e] isoindole; nmr spectrum: τ, 7.I-8.5 (rn,9). 2-Cyclopentylmethyl-l,2,3i 5"tetrahydro~5,9b-o-bensenobenz[ e] isoindole; n.p. 110-111°C; nmr spectrum: τ 7.3-9-0 (in, 11).

Anal. Calcd. for C) 88-°3 H, 7-70; IT, ¾.28 Found: C, 87.68; H, 7-75; N, ^.½3- 5-Methyl-2 -cyclohexylmethy1-1 ,2,3 , 5-tetrahydro- 5 , 9b- o-benzenobenz[e]isoindole ; nmr spectrum: τ 3.9 (t, 2Hz, 1) (proton at C-U; the response at 4.6-5.0 is missing); 7.6 (d, 6Hz, 2); 7.9 (s, 3); 8.0-9.5 (m, 11). 2-(2-Cyclohexylethyl)-l ,2 , 3 , 5-tetrahydro-5 ,9b-o- benzenobenzCe ]isoindole ; nmr spectrum: τ 7.1-9.5 (m, 15). 2-(A3-Cyclohexenylmethyl)-l,2 ,3 , 5-tetrahydro-5 ,9b- o-benzenobenz[e]isoindole ; nmr spectrum: τ 4.3 (m, 2); 7.5- 9.0 (m, 9). 2-Cyclcheptylwethyi-l, 2 ,3 , 5~tetrahydro ~5,9 ~Q-benzenobenz[ e] isoindole nmr spectrum τ 7·5~9·2 (m,15). ^ 2-Benzyl-1,2,3, 5~tetrahydro-5,9b-o_-benzenoben^-[ejisoindole: rmr spectrum: τ 2.4-3.0 (m, 5); 6.3 (s,2). 2~( l- araantyl ethyl) -1,2,3, 5~tetrahydro~5,9b-o_-benzenobenz[e]isoindole; nmr spectrum: τ 7.6 (s,2); 7.5-8.5 (m, 15). 2-(2-Phenylethyl) -1,2,3, 5~tetrahydro-5,9b-o-benzeno-benz[e]isoindole nmr spectrum: τ 2.6-3.1 (m,5)j 7·° EXAMPLE 8 2-Cyclohexylmethyl-l ,2 , 3 ,5-tetrahydro-5 ,9b-o-benzenobenz [elisoindole cyclohexanecarbonyl chloride in place of cyclopropanecarbonyl chloride, there is obtained in turn: 2-Gyclohexanecarbonyl-l ,2 ,3 ,5-tetrahydro-5 ,9b- benzenobenz-[e ]isoindole , mp 215-217°.

Anal. Calcd. for C2sH2sN0: C, 84.47; H, 7.09; N, 3.94 Found: C, 84.36; H, 7.05; N, 4.00. 2-Cyclohexylmethyl-l ,2 , 3 ,5-tetrahydro-5 ,9b-o- benzenobenz[e]isoindole , mp 157-158°. NMR spectrum τ 2. 3.5 (m, 9); 4.9 (d, 2Hz , 2); 7.5 (d, 6Hz, 2) and 7.7-9.5 (m, 11).

Anal. Calcd. for C25H27N: C, 87.93; H, 7.97; N, 4.10 Found: C, 87.80; H, 7.66; N, 4.29. 2-Chloro-9-anthraldehyde and 2 ,6-dimethoxy-9-anthraldehyde , reported in the literature , can be employed as starting materials according to the general procedure of Examples 3 and 6 to obtain the correspondingly substituted 9,12-bridged ethenoanthracenes (I) as reaction products.

The following substituted 9-anthroic acids , described in the literature, can be employed as starting materials according to the general procedures of Examples 1 and 2 to obtain the correspondingly substituted novel 9,12-bridged ethenoanthracenes (I) as reaction products: l-chloro-9-anthroic acid, 2-chloro-9-anthroic acid, l,5-dichloro-9-anthroic acid, 2-methyl-9-anthroic acid, 3-chloro-9-anthroic acid, 1 ,<+-dichloro-9-anthroic acid, 2 ,5-dichloro-9-anthroic acid, 4 ,5-dichloro-9-anthroic acid.

The compounds of this invention are all useful as polymerization inhibitors for the free radical polymerization of vinyl compounds. This utility is demonstrated with respect to inhibition of the polymerization of acrylonitrile .

EXAMPLE A In a Carius tube is placed 0.5 ml of distilled acrylonitrile , 2 ml of toluene, 20 mg of azobis (isobutyro-nitrile) initiator and 70 mg of 2-methyl-3 ,5-dihydro- 5 ,9b-o-benzenobenz[e]isoindol-l(2H)-one (Example 2). The tube is degassed, sealed under vacuum and shaken at room temperature overnight. No polyacrylonitrile is formed. In a control experiment in which the compound of Example 2 is omitted, solid polyacrylonitrile separates from the solution When the following compound is similarly employed as an inhibitor, polymerization of acrylonitrile does not occur : 2-Methyl-l ,2 ,3 ,5-tetrahydro-5 ,9^b-o-benzenobenz-[e]isoindole (Example 5).

Claims (11)

1. Compounds of the formula wherein R and R are the same or different and are each hydrogen, lower alkyl, or halogen with the proviso that at least one of R1 and R2 is hydrogen, X is selected from 3 one of the following groups -CH=NCH2-; -CON(R )CH2~; and 3 3 -CH2N(R )CH2- where R is hydrogen, alkyl of up to 12 carbon atoms, lower alkenyl attached to N by a saturated carbon atom, cydloalkyl of 3-9 carbon atoms, alkylmethyl of 4-10 carbons ^cycloalkenylmethyl , adamantylmethyl, benzyl, or 3-phenylethyl.

2. A compound of Claim 1 having the formula: 3 3 wherein X is -CH2 - NR - CHa- and R is H, alkyl of up to 12 carbon atoms, cycloalkylmethyl of to 10 carbon atoms or benzyl.

3. The compound of Claim 2 wherein R1 and R2 are each hydrogen.

4. ¼. The compound of Claim 2 wherein R5 is cyclo-alkyl methyl of 4 to 10 carbon atoms.

5. The compound of Claim 2 wherein R is cyclo-butyl methyl.

6. The compound of Claim 2 wherein R5 is cyclo-pentyl methyl.

7. The compound of Claim 2 wherein R5 is cyclo-hexyl methyl.

8. The compound of Claim 2 wherein R5 is cyclo-heptyl methyl.

9. The compound of Claim 2 wherein R5 is lower alkyl.

10. The compound of Claim 3 wherein R5 is cyclopentyl methyl.

11. The compound of Claim 2 wherein Rs is hydrogen .