Category: 21850-12-4

Some reactions of 4,7,8,9-tetrahydroisoindoline and perhydroisoindole was written by Rice, Leonard M.;Grogan, Charles H.. And the article was included in Journal of Organic Chemistry in 1955.Quality Control of Octahydro-1H-isoindole This article mentions the following:

Reduction of 150 g. cis-螖⁴-tetrahydrophthalimide with 60 g. LiAlH₄ in 1.7 l. Et₂O 24 hrs. by the Soxhlet apparatus method and decomposition of the excess LiAlH₄ with H₂O gives 60 g. 4,7,8,9-tetrahydroisoindoline (I), b₁₅ 76-80掳, b₂₆ 90-3掳 (phenylthiourea derivative, m. 164-5掳; “naphthylurea derivative,” m. 216-17掳; phenylurea derivative, m. 152.5-3.5掳; p-bromophenylsulfonamide derivative, m. 102-3掳; HCl salt, m. 131.5-2.5掳). Hydrogenation of 32 g. I in 300 cc. MeOH with 0.5 g. PtO₂ at 20掳 gives perhydroisoindole (HCl salt, m. 123.5-5掳; picrate, m. 162-3掳; phenylurea derivative, m. 133-5掳; phenylthiourea derivative, m. 176-8掳; naphthylurea derivative, m. 182-3.5掳). Refluxing 17.7 g. I and 5.4 g. CH₂ClCN 4 hrs. in 100 cc. PhMe gives 69% N-(cyanomethyl)-I (II), b_0.4 80掳, b_0.2 67掳, n_D²⁰ 1.5031. Adding dropwise 6 g. II in 100 cc. Et₂O to 2 g. LiAlH₄ in 400 cc. Et₂O, refluxing the mixture 2 hrs., adding H₂O, and distilling the residue of the Et₂O solution give 6.1 g. N-(尾-aminoethyl)-I, b_3.5 97-101掳, n_D²⁰ 1.5067 (di-HCl salt, rectangular plates, m. 180-80.5掳). Subjecting 0.1 molar amounts of I and PhCOMe to the Mannich reaction according to Blicke (C.A. 36, 5766.6) gives 60% Ph 尾-(4,7,8,9-tetrahydro-2-isoindolinyl)ethyl ketone-HCl, m. 153-5掳. Passing 8.4-8.8 g. ethylene oxide into 25.5 g. I in 500 cc. MeOH at 0掳 and keeping the mixture overnight at 20掳 give 63% N-(尾-hydroxyethyl)-I (III), b₁ 85-90掳. Hydrogenation of 7 g. III in 100 cc. MeOH 1 hr. with 5% Pd-C gives 5.5 g. N-(尾-hydroxyethyl)perhydroisoindole (IV), b_0.75 78-82掳 [p-nitrobenzoate-HCl (V), 100%, m. 171.5-2.5掳]. Refluxing 5.01 g. III in 45 cc. C₆H₆ 2 hrs. with 5.57 g. p-O₂NC₆H₄COCl in 45 cc. C₆H₆ gives almost 100% 尾-(4,7,8,9-tetrahydroisoindolinyl)ethyl p-nitrobenzoate-HCl (VI), m. 157-8掳. Reduction of 5 g. VI in 400 cc. MeOH over 5% Pd-C at 20掳 gives 尾-(perhydroisoindolyl)ethyl p-aminobenzoate-HCl, m. 229-31掳 which is also obtained on reduction of V. Refluxing 32.03 g. I in 150 cc. PhMe 4 hrs. with 15.9 g. CH₂ClCO₂Et, filtering off the I.HCl formed, and distilling the residue of the evaporated filtrate give 21 g. Et (4,7,8,9-tetrahydroisoindolinyl)acetate (VII), b_0.2 73-5掳. Treating 10.15 g. VII in 40 cc. absolute EtOH 3 days with the calculated amount of _0.5N alc. KOH, adding the calculated amount of HCl, and evaporating the filtered solution give 4,7,8,9-tetrahydroisoindolinylacetic acid, crystallizing with 1 H₂O, m. 146-7掳. Refluxing 10.5 g. VII in 50 cc. 95-100% (CH₂NH₂)₂ 8 hrs. and fractionally distilling the mixture give N-(₂-imidazolemethyl)-4,7,8,9-tetrahydroisoindoline, b_0.5 173-9掳, which, with alc. HCl, gives the di-HCl salt-H₂O, m. 176.5-8.5掳. Treating 8.5 g. IV in 50 cc. C₆H₆ overnight with 11.5 g. Ph₂CHCOCl, refluxing the mixture 2 hrs., extracting the cooled C₆H₆ solution with 10% HCl, making the acid solution alk., extracting with Et₂O, and treating the residue of the Et₂O extract in EtOH with alc. HCl give 尾-(perhydroisoindolyl)ethyl diphenylacetate-HCl, m. 129-30掳. Adding dropwise 26.55 g. acrylonitrile in C₆H₆ to 50.08 g. N-methylpiperazine in 150 cc. C₆H₆, refluxing the mixture several hrs., and keeping it overnight gives 79.5% N-methyl-N’-(cyanoethyl)piperazine, b_0.3 68-72掳, n_D²⁰ 1.4744, which (58 g.), reduced with LiAlH₄, gives 23 g. N-methyl-N’-(纬-aminopropyl)piperazine (VIII), b_0.3 52掳. Adding 22 g. VIII to 20 g. cis-螖⁴-tetrahydrophthalic anhydride causes an exothermic reaction; the mixture, heated 2 hrs. at 170-90掳, gives 33 g. N-(纬-tetrahydrophthalimido)propyl-N’-methyl-piperazine (IX), b_0.2 160-5掳 [di-HCl salt m. 258-9掳 (decomposition)]. Adding slowly 30 g. IX in Et₂O to 15 g. LiAlH₄ in 1 l. Et₂O and stirring the solution several hrs. give 2-[N-methyl-N’-(纬-piperazinopropyl)]-I, b_0.1 136-42掳 [tri-HCl salt, m. 270-1掳 (decomposition); trisquaternary methonium salt m. 217-18掳]. In the experiment, the researchers used many compounds, for example, Octahydro-1H-isoindole (cas: 21850-12-4Quality Control of Octahydro-1H-isoindole).

Octahydro-1H-isoindole (cas: 21850-12-4) belongs to indole derivatives. Indole exists overwhelmingly in the 1H-indole form as do other simple indoles. In addition to indole, the strain-release chemistry worked for numerous substrates including amines, alcohols, thiols, carboxylic acids, imidazoles, and pyrazoles.Quality Control of Octahydro-1H-isoindole

Referemce:
Indole alkaloid derivatives as building blocks of natural products from聽Bacillus thuringiensis聽and聽Bacillus velezensis聽and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles