7-Bromobutyronitrile

The submitter reports that an equivalent number of moles of 7-bromobutyronitrile or a mixture of 7-chloro- and 7-bromo-butyronitrile may be substituted for 7-chlorobutyronitrile. If the bromo compound is used the reaction mixture should be refluxed six hours and it is necessary to filter off the sodium bromide just before the final vacuum distillation. 

Phenylisonipecotic acid ethyl ester 2,2-Diphenyl-4-bromobutyronitrile... 

A mixture of 23 parts of the ethyl ester of 4 phenylisonipecotic acid and 15 parts of 2,2-diphenyl-4-bromobutyronitrile in 19 parts of xylene is heated for 24 hours at 100°-120°C and then cooled and filtered to remove the precipitate of the hydrobromide of the ethyl ester of 4-phenylisonipecotic acid. The filtrate is then extracted with dilute hydrochloric acid and the extract is rendered alkaline by addition of concentrated aqueous potassium hydroxide and extracted with ether. This ether extract is treated with gaseous hydrogen chloride. The resulting precipitate is collected on a filter. The hydrochloride of the ethyl ester of 2,2 diphenyl-4-(4 -carboxy-4 -phenyl-1 -piperidino) butyronitrile thus obtained melts at about 220.5-222°C. See Meperidine hydrochloride for synthesis of 4-phenyl-isonipecotic acid ethyl ester. 

Diphenoxylate Diphenoxylate, ethyl ester of l-(3-cyano-3,3-diphenylpropyl)-4-phenylpiperidine-4-carboxylic acid (3.1.58), is also a drag of 4-phenylpiperidine series. In practice there are two ways of making it. The first way is by the alkylation of the ethyl ester of 4-phenylpiperidine-4-carboxylic acid (3.1.56) with 2,2-diphenyM-bromobutyronitrile, which in turn is synthesized from l-benzyl-4-phenyM-cyanopiperidine. The product undergoes ethanolysis in the presence of acid, followed by benzylation. The second way is a synthesis accomplished by alkylation of diphenylacetonitrile using ethyl ester of l-(2-chloroethyl) -phenylpiperidine-4-carboxylic acid (3.1.57), which is synthesized by... 

Chlorobutyronitrile (Practical, Mixture with 4-Bromobutyronitrile) 4-Chlorobutyronitrile... 

Trialkylammonium salts of the N-unsubstituted tetrazoles 231 are equally applicable as substrates in reactions both with haloalkyls and unsaturated compounds. These reactions, as already mentioned, lead mainly to formation of Nz-isomers. For instance, the reaction of 5-phenyltetrazole triethylammonium salt 231 (generated in situ from 5-phenyltetrazole and triethylamine) in acetonitrile with y-bromobutyronitrile (alkylation) or with acrylonitrile (Michael s method) afforded the corresponding Nz-substituted derivatives 254 and 255 in acceptable yields (Scheme 26) <2002CHE986>. 

Even though the energy of activation may be theoretically related to bond dissociation energy, the comparative rates and correlation, adequate parameters were found for the interpretation of the substituent effect. An isomerization of equation 38 and an equilibrium process of the primary products formed from 4-bromobutyronitrile are shown in a... 

Bromobutyronitrile was purchased from Aldrich Chemical Company, Inc., and was freshly distilled (bp 95-98°C, 15 mm). 

Pyridazines were obtained also by photolysis of 1-phenyl-l-vinyl azide in the presence of iron pentacarbonyl (3,6-di-phenylpyridazine was obtained in 1.1% yield) (78HCA589) or by thermal decomposition of an allenic hydrazonate (81JA7011). Acetylenic hydrazides can be transformed into pyridazines [84BSF(2)129], and thermal cyclization of dialkali metal salts of cu-hydroxyketone tosylhydrazones afforded pyridazines in moderate yield (85TL655). Propionyl phenylhydrazine, after reaction with 4-bromobutyronitrile, converts into a pyridazine (87SC1253). 

A mixture of 1 kg. of methanol, 65 g. (1.0 mole) of potassium cyanide, and 404 g. (2.0 moles) of trimethylene bromide is heated to reflux on a steam bath for 7-8 hours. The precipitated potassium bromide is filtered off, and the methanol is distilled from the filtrate. Fractional distillation of the residual oil gives 175 g. (0.87 inole) of unreacted trimethylene bromide, b.p. 70-72°/20 nun, and 70 g. (42% based on unrecovered trimethylene bromide) of y-bromobutyronitrile, b.p, 100-102°/20 mm. 

The use of microwave irradiation in the Michaelis-Arbuzov reaction increases both reaction rates and yields. Under these conditions, a high yield of diethyl 3-cyanopropylphosphonate (75%) is obtained from triethyl phosphite and 4-bromobutyronitrile.- ... 

Bromobutyronitrile and diethylamine give analogously 86% of 4-(diethylamino)butyr-aldehyde, b.p. 101-103°/21 mm, nD20 1.4351. 

Clark and Mosher512 obtained a 96.7% yield of 4-(diethylamino)butyronitrile from 4-bromobutyronitrile after addition of 0.05 mole- % of sodium iodide which aided reaction. 

Ethyl-4-phenylisonipecotate is perpared as described above in pethidine hydrochloride, which is then condensed with 2, 2-diphenyl-4-bromobutyronitrile by refluxing together in toluene using an excess of the ester. 

---