Description
2-(Bromomethyl)benzonitrile reacts with 2H-tetrazole in the presence of KOH to yield 4-[(2H-tetra-zol-2-yl)meth-yl]benzonitrile. It undergoes base-promoted condensation reaction with homophthalic anhydride to yield 6,11-dihydro-5H-indeno[1,2-c]isoquinolin-5-one.
Chemical Properties
White to light yellow crystal powder
Uses
2-(Bromomethyl)benzonitrile is an intermediate in the synthesis of Alogliptin, an oral antihyperglycemic agent that is a selective inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4). Antidiabetic agent.
Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package.
General Description
2-(Bromomethyl)benzonitrile reacts with 2
H-tetrazole in the presence of KOH to yield 4-[(2
H-tetra-zol-2-yl)meth-yl]benzonitrile. It undergoes base-promoted condensation reaction with homophthalic anhydride to yield 6,11-dihydro-5
H-indeno[1,2-
c]isoquinolin-5-one.
Synthesis
General procedure for the synthesis of 2-cyanobenzyl bromide from o-toluonitrile: Azobisisobutyronitrile (AIBN, 29.25 mmol) was added to a solution of 2-methylbenzyl cyanide (325 mmol) and N-bromosuccinimide (NBS, 346 mmol) in carbon tetrachloride (300 mL). The reaction mixture was heated at 90°C for 2 h and subsequently cooled to room temperature. The precipitated solid was removed by filtration and the filtrate was washed with saturated aqueous sodium bicarbonate solution (4 x 120 mL), dried over sodium sulfate and concentrated. The resulting solid was washed with hexane (4 x 500 mL) and dried to give 2-(bromomethyl)benzonitrile in 57% yield as a yellow solid. A solution of 2-(bromomethyl)benzyl cyanide (214 mmol) in dimethyl sulfoxide (40 mL) was slowly added to a solution of ethyl 2-hydroxyacetate (431 mmol) and sodium ethoxide (215 mmol) in dimethyl sulfoxide (14.5 mL) over 90 minutes. The reaction mixture was kept at room temperature for 1 hour, followed by heating at 65°C for 5 hours and finally cooled to room temperature. The reaction mixture was diluted with ice water (50 g), extracted with ether (3 x 500 mL) and the combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by column chromatography (petroleum ether/ethyl acetate, 100:1 to 50:1) to give [(2-cyanobenzyl)oxy]ethyl acetate as a yellow oil.
Purification Methods
Purify the nitrile by steam distillation. Extract the distillate with Et2O, dry the extract (Na2SO4), evaporate and distil the residue. The solidified distillate can be recrystallised from pet ether or cyclohexane. NMR (CDCl3) : 7.8-7.2 (m 4H), 4.62 (s, 2H), IR max 2238 cm1 . [Drory Chem Ber 24 2570 1891, Borsche et al. Chem Ber 74 685 1934, Buckley et al. Aust J Chem 22 594 1969, Beilstein 9 III 2312.] LACHRYMATORY.
References
[1] Organic Process Research and Development, 1998, vol. 2, # 4, p. 261 - 269
[2] Chemistry - A European Journal, 2002, vol. 8, # 9, p. 2000 - 2004
[3] Journal of Organic Chemistry, 2014, vol. 79, # 23, p. 11592 - 11608
[4] Patent: WO2009/55437, 2009, A2. Location in patent: Page/Page column 61; 62
[5] Dyes and Pigments, 2014, vol. 102, p. 63 - 70
