Govindachari, T. R.; Rajappa, S.; Sudarsanam, V. published an article in 1963, the title of the article was A synthesis of ellipticine.Application In Synthesis of 3-Amino-2,5-dimethylbenzonitrile And the article contains the following content:
2,5-Dimethyl-4-nitrobenzoic acid (4.5 g.) was converted into the Et ester [by refluxing in 70 ml. absolute EtOH containing 8 ml. H2SO4 (d. 1.84) 6 hrs.] (4 g.), b0.1 120-3°, which was reduced catalytically (30 lb./in.2 H, Adams catalyst; 1.5 hrs., room temperature) to Et 4-amino-2,5-dimethylbenzoate (I), m. 78-80° (C6H6-petr. ether). I on diazotization followed by SnCl2 reduction afforded Et 4-hydrazino-2,5-dimethylbenzoate (II), m. 135-6° (C6H6-petr. ether). A mixture of 1.1 g. II, 0.6 g. cyclohexanone (III), 15 ml. EtOH, and 2 ml. HCl (d. 1.16) was refluxed (steam-bath, 4 hrs.) and poured into 100 ml. H2O to give 0.8 g. Et 1,2,3,4-tetrahydro-5,8-dimethylcarbazole-6-carboxylate (IV) (washed, dried and sublimed at 170-80°/0.001 mm.), m. 157-9° (C6H66-petr. ether). IV (0.5 g.) in 10 ml. Decalin was heated (220°, 2 hrs.) with Pd-C (5%, 0.5 g.), the mixture filtered, catalyst washed with Me2CO, and the combined filtrates evaporated in vacuo. Chromatography of the residue in C6H6 over Al2O3 (basic Al2O3 of Riedel deHahn was used throughout) afforded 0.17 g. Et 1,4-dimethylcarbazole-3-carboxylate (V), m. 150-2° (C6H6-petr. ether); λ 245, 275, 310, 335 mμ (log ε 4.45, 4.56, 3.82, 3.44). V (1 g.) in 50 ml. dry ether was added to a suspension of 0.5 g. LiAlH4 in dry ether with stirring, the mixture stirred 2 hrs., decomposed (moist ether-H2O), and the organic phase dried and distilled to give 0.6g, 1,3,4-trimethylcarbazole (VI), m. 145-6° (C6H6-petr. ether). Its structure was indicated by infrared (IR) spectrum [only a single sharp band at 2.8 μ (NH)], analysis, and by the recovery of VI after treatment with Ac2O and C5H5N. 2-Cyano-5-nitro-p-xylene on reduction (30 lb./in.2 H; Pd-C; room temperature, 1 hr.) gave 5-amino-2-cyano-p-xylene (VII), m. 158-60° (C6H6); Ac derivative m. 190-2° (MeOH). Diazotization of VII followed by SnCl2 reduction afforded 2-cyano5-hydrazino-p-xylene, m. 161-3° (MeOH), which on condensation with III (as for IV) gave 6-cyano-1,2,3,4-tetrahydro-5,8-dimethylcarbazole (VIII), m. 270-3° (Me2CO), λ 248, 280 mμ (log ε 4.94, 3.88). Dehydrogenation (Pd-C) of VIII yielded 3-cyano-1,4-dimethylcarbazole (IX), m. 249-51° (Me2CO), λ 245, 270, 320, 335 mμ (log ε 4.59, 4.68, 3.56, 3.46). IX (0.4 g.), 30 ml. ethylene glycol and 10 g. KOH in 10 ml. H2O was refluxed 20 hrs., poured into 100 ml. H2O, filtered, the filtrate acidified (HCl) and extracted with EtOAc, and the extract washed (H2O), dried, and distilled to give 0.1 g. 1,4-dimethylcarbazole-3-carboxylic acid (X), m. 253-5° (Me2CO). IX (0.5 g.) in 100 ml. MeOH and 5 g. KOH in 5 ml. H2O was shaken 6 hrs. at room temperature with H (40 lb./in.2) (Raney Ni) and MeOH was removed from the filtered solution to give 0.4 g. 3-aminomethyl-1,4-dimethylcarbazole (XI), m. 210-12°. The Schiff base obtained by condensation of XI with glyoxal semi-diethyl acetal could not be cyclized to ellipticine (XII). Alternatively, 3,6-dimethyl-2-nitrobenzaldehyde was converted into its oxime, which on dehydration (Ac2O) yielded 2-cyano-3-nitro-p-xylene (XIII), m. 85° (C6H6-petr. ether); ν 4.5 μ (CN). XIII on reduction (25 lb./in.2 H; Pd-C) gave 3-amino-2-cyano-p-xylene (XIV), b0.3 106-8°; ν 2.75, 2.85 μ (NH2) and 4.5 μ (CN); acetate m. 74-5° (C6H6-petr. ether). A suspension of 8.4 g. XIV in 40 ml. HCl (d. 1.7) and 18 ml. H2O was diazotized (0°) with NaNO2 (4.3 g. in 15 ml. H2O), the solution added dropwise with stirring to a solution of 12 g. CuCl2 in 50 ml. HCl (d. 1.17) at 0°, the solution allowed to warm to room. temperature left overnight, heated (60°), cooled, extracted with ether, and the extract washed with dilute HCl, H2O, dilute NaOH solution and again with H2O, dried, and evaporated Removal in vacuo yielded 8.3 g. 3-chloro-2-cyano-p-xylene (XV), b0.3 84-6°, m. 72-4° (petr. ether); ν 4.5 μ (CN). KNO3 (2.5 g.) in 35 ml. H2SO4 (d. 1.84) at 0° was added with stirring to 4 g. XV in 25 ml. H2SO4 (d. 1.84), and the mixture stirred 2 hrs. at 5° and poured onto crushed ice to give 4.1 g. 2-chloro-3-cyano-5-nitro-p-xylene (XVI), m. 86-8° (aqueous EtOH). Pd-CaCO3 (5%; 2 g.) was shaken with H (10 lb./in.2, 10 min.). A solution of 2 g. XVI in 100 ml. EtOH and 20 g. NH4Ac was then added and the whole shaken with H (30 lb./in2., 1 hr.); EtOH removed from the filtrate, the residue diluted with H2O, extracted with ether, and the extract washed with NaHCO3 and H2O, dried, and distilled; the residue was sublimed (140°/0.01 mm.) to give 1 g. 2-amino-6-cyano-p-xylene (XVII), m. 118-20° (C6H6-petr. ether); ν 2.85 (NH2) and 4.5 μ (CN). Diazotization of XVII followed by SnCl2 reduction afforded 6-cyano-2-hydrazino-p-xylene (XVIII), m. 173-5° (MeOH). Refluxing 1.4 g. XVIII, 1 g. III, 20 ml. EtOH, and 6 ml. HCl (d. 1.17) gave 0.9 g. 7-cyano-1,2,3,4-tetrahydro-5,8-dimethylcarbazole (XIX), m. 229-31° (EtOH); ν 2.9 (NH) and 4.5 μ (CN), λ 228,250,295, 330 mμ (log ε 4.43, 4.45, 4.04, 4.05); it gave unsatisfactory C analytical values. XIX (1.3 g.) on refluxing with aqueous KOH (5 g. in 5 ml. H2O) and 80 ml. ethylene glycol (as for X) gave 1.3 g. 1,2,3,4-tetrahydro-5,8-dimethylcarbazole-7-carboxylic acid (XX), m. 241° (decomposition) (MeOHC6H6), which with EtOH saturated with HCl gave the Et ester (XXI), m. 137-41° (C6H6-petr. ether); ν 2.85 (NH) and 5.9 μ (CO2Et). XXI on heating (210°, 15 hrs.) with 5% Pd-C in a CO2 atm. gave 0.6 g. Et 1,4-dimethylcarbazole-2-carboxylate (XXII), m. 118-20° (C6H6-petr. ether), λ 250, 305, 350 mμ (log ε 4.69, 4.33, 3.7). Esterification (CH2N2 in ether) of XX gave Me 1,2,3,4-tetrahydro-5,8-dimethylcarbazole-7-carboxylate, m. 158-60° (C6H6), which on heating in Decalin (200°, 15 hrs.) with Pd-C gave Me 1,4-dimethylcarbazole-2-carboxylate (XXIII), m. 150-2° (C6H6-petr. ether), ν 2.9 (NH) and 5.85 μ (CO2Me). XXIII (1 g.) on refluxing (steam-bath, 2 hrs.) with KOH (2.5 g. in 2 ml. H2O) and working up as usual gave 0.8 g. 1,4-dimethylcarbazole-2-carboxylic acid, m. 238-40° (Me2CO). LiAlH4 reduction (as in VI) of XXIII (in tetrahydrofuran) gave 2-hydroxymethyl-1,4-dimethylcarbazole (XXIV), m. 146-8° (C6H6), ν 2.7 (OH) and 2.8 μ (NH). Oxidation of XXIV with C5H5N-Cr2O3 (0°, stirred 30 min., left at room temperature 20 hrs.) gave 1,4-dimethylcarbazole-2-aldehyde (XXV), m. 201-3° (MeOH-C6H6), ν 2.9 (NH) and 5.95 μ (CHO). XXV (0.9 g.) in 30 ml. HOAc was refluxed 2 hrs. with 3 ml. MeNO2 and 1 g. NH4Ac; the mixture on pouring into H2O gave 0.9 g. 1,4-dimethyl-2-(2-nitrovinyl)carbazole (XXVI), m. 273-5° (decomposition) (EtOAc). Reduction of XXVI with LiAlH4 afforded 2-hydroxymethyl-1,4-dimethylcarbazole (XXVII), m. 196-8° (MeOH-C6H6). XXVII (0.5 g.) was heated with 20 ml. HCO2Et in a sealed tube (120°, 6.5 hrs.), excess HCO2Et distilled, and the residue chromatographed on Al2O3 to give 0.15 g. 2-(2-formamidoethyl)-1,4-dimethylcarbazole (XXVIII), m. 183-5° (MeOH-C6H6); ν 2.85 (NH) and 5.95 μ (NHCHO). XXVIII (0.15 g.) was cyclized by refluxing (150°, 0.5 hr.) with 5 ml. POCl3 in 130 ml. dry xylene, xylene was removed in vacuo, the residue extracted with hot dilute HCl, the filtered acid extract was basified (K2CO3), extracted with CHCl3, and the extract washed (H2O), dried (Na2SO4), and distilled to give 30 mg. 3,4-dihydro-5,11-dimethyl-6H-pyrido[4,3-b]carbazole (XXIX) (1,2-dihydroellipticine), m. 292-6°, identical with an authentic sample (Buchi, et al., CA 56, 11631f) in IR ultraviolet (UV), m. p. and mixed m. p., and Rf(1: 1 EtOH-C6H6) values. Dehydrogenation of 30 mg. XXIX with Pd-C (5%; 50 mg.) in Decalin (220°, 3 hrs., CO2 atm.) gave 5 mg. XII, m. 310-14° (decomposition) (EtOAc), identical with an authentic sample (Goodwin, et al., CA 53, 22046f) (m. p., mixed m. p., IR and UV spectra). XII was also synthesized recently by Cranwell and Saxton (CA 57, 3499a; 59,681e) by a different route. The experimental process involved the reaction of 3-Amino-2,5-dimethylbenzonitrile(cas: 90557-28-1).Application In Synthesis of 3-Amino-2,5-dimethylbenzonitrile
3-Amino-2,5-dimethylbenzonitrile(cas:90557-28-1) belongs to nitriles. Some nitriles are manufactured by heating carboxylic acids with ammonia in the presence of catalysts. This process is used to make nitriles from natural fats and oils, the products being used as softening agents in synthetic rubbers, plastics, and textiles and for making amines.Application In Synthesis of 3-Amino-2,5-dimethylbenzonitrile
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts