0,7-Diphenylacetonitrile

The mechanism of the reaction is unknown. The stereospecificity observed with (E)- and (Z)-l-methyl-2-phenylethylene points to a one-step reaction. The very low Hammett constant, -0.43, determined with phenylethylenes substituted in the benzene ring, excludes polar intermediates. Yields of only a few percent are obtained in the reaction of aliphatic alkenes with (52). In the reaction of cyclohexene with (52), further amination of the aziridine to aminoaziridine (99) is observed. Instead of diphenylazirine, diphenylacetonitrile (100) is formed from diphenylacetylene by NH uptake from (52) and phenyl migration. 

Synthesis of the intermediate aminonitrile for methadone by (I r giospecific route served to confirm the structure. Alkyla-I Lon of diphenylacetonitrile with l-chloro-2-propanol affords the. ilcohol, 120, free of isomeric products (although it is possible here, too, to imagine cyclization of the halide prior to alkyla-lion). The hydroxyl is then converted to the bromide (121) by... 

Replacement of the ketone by an amide leads to Increased potency. Hydrolysis of nitrile, 133 (obtained by alkylation of diphenylacetonitrile with the morpholine analog of the chloro-amine used in the original preparation of methadone), affords acid, 134. Conversion to the acid chloride followed by reaction with pyrrolidine affords racemoramide (135) Separation of the (+) isomer by optical resolution gives dextromoramide, an analgesic an order of magnitude more potent than methadone. 

A not uncommon side effect observed with morphine and some of the other narcotic analgesics is constipation due to decreased motility of the gastrointestinal tract. It proved possible to so modify pethidine as to retain the side effect at the expense of analgesic activity. Relief of diarrhea, it will be realized, is a far from trivial indication. Alkylation of the anion from diphenylacetonitrile (95) with ethylene dibromide gives the intermediate, 96. Alkylation of normeperidine (81) with that halide... 

Diphenylacetonitrile is condensed with 2dimethyl-amino)-2,2-diphenyl valeronitrile. It is then reacted with ethyl magnesium bromide and then hydrolyzed using HCl to give methadone hydrochloride. 

Oxyphenisatin acetate Diphenylacetic acid chloride Diphenpyramide Thiphenamil HCI Diphenyl acetone Diphenadione Diphenylacetonitrile Doxapram HCI Methadone HCI Diphenylacetyl chloride Piperidolate... 

A more highly substituted pyrrolidone, doxapram, shows activity as a respiratory stimulant. Preparation of this agent involves an interesting rearrangement, which in effect results in a ring exchange reaction. Alkylation of the anion from diphenylacetonitrile with the chloropyrrolidine 14 affords 15. Hydrolysis of the nitrile function leads to the... 

Certain esters have often been employed in attempts to confer organ selectivity to molecules possessing carboxyl functions. Thus, for example, treatment of piperidinecarboxylic acid 76 with N-hydroxysuccinimide and DCC affords the ester 77. In a convergent synthesis, the anion from diphenylacetonitrile (78) is alkylated with dibromoethane to afford the bromide 79. Alkylation of the piperidine derivative 77 with that halide 79 gives the anti-diarrheal agent difenoximide (80). The same sequence starting with the phenoxyethyl ester 81 gives fetoxylate (82). 

The diphenylacetonitrile is purified by dissolving in hot isopropyl alcohol (1 ml per g of product) and cool slowly. After complete crystallization, filter and wash with cold isopropyl alcohol (0.2 ml per g). Yield 97-100 g, mp 74-75°. 

Methadone Methadone, 6-dimethylamino-4,4-dephenyl-3-heptanone (3.1.37), is synthesized by alkylation of diphenylacetonitrile using l-dimethylamino-2-propylchloride in the... 

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... 

Doxapram Doxapram, l-ethyl-4-(2-morpholinoethyl)-3,3-diphenyl-2-pyrrolidinone (8.2.4), is synthesized in the following manner. Diphenylacetonitrile in the presence of sodium amide is alkylated with l-ethyl-3-chlorpyrrolidine, giving (l-ethyl-3-pyrrolidinyl) diphenylacetonitrile (8.2.1). Acidic hydrolysis of the nitrile group gives (l-ethyl-3 pyrrolidinyl)diphenylacetic acid (8.2.2). Reacting this with phosphorous tribromide... 

Isopropamide Isopropamide, (3-carbamoyl-3,3-diphenylpropyl)di-tiO-propylmethyl ammonium iodide (14.1.25), is synthesized by alkylating diphenylacetonitrile with di-/io-propylaminoethylchloride in the presence of sodium amide, and the subsequent hydrolysis of the nitrile group of the resulting compound (14.1.23) to an amide group (14.1.24). Alkylation of this compound with methyliodide gives isopropamide (14.1.25) [19-22]. 

The adduct could also be synthesized from preformed benzophenone. Thus, 5.2 mmoles of benzophenone reacted in 25 ml. of DMSO (80% )-tert-butyl alcohol (20%) containing 5.7 mmoles of potassium tert-butoxide to give a 93% yield of the adduct in 15 minutes at 25°C. The DMSO-benzophenone adduct was also isolated by benzene extraction of the hydrolyzed and acidified oxidates of benzhydryl chloride, benzhydryl bromide, benzhydryl amine, diphenylacetonitrile, and 1,1-diphenylace-tone in DMSO (80% )-tert-butyl alcohol (20% ). 

Diphenylacetic acid has been obtained by the reduction of benzilic acid with hydriodic acid and red phosphorus 1 by the treatment of phenylbromoacetic acid with benzene and zinc dust,2 or with benzene and aluminum chloride 3 by the hydrolysis of diphenylacetonitrile 4 by heating a-diphenyldichloroethyl-ene with alcoholic sodium ethylate 5 by heating benzilic acid 6 from diphenylmethane, mercury diethyl, sodium and carbon dioxide 7 by the oxidation of a,a,5,S-tetraphenyl- 8-butine 8 by the decomposition of some complex derivatives obtained from diphenylketene 9 by the hydrolysis of diphenyl-5,5-hydan-toin 10 by the treatment of diphenylbromoacetic acid with copper 11 by the oxidation of dichlorodiphenylcrotonic acid.12... 

Inhibition of intestinal peristalsis rates among one of the more common effects of morphine that are not directly related to its analgesic activity. The finding that meperidine (21-4) shares this effect led to the development of a highly substituted derivative, diphenoxilate (22-3), that also inhibits intestinal motility and thus acts as an antidiarrheal agent. The side chain in (22-3) is prepared by alkylation of the anion from diphenylacetonitrile with 1,2-dibromoethane to give the bromoethyl... 

An unusual rearrangement provides the key to the preparation of a highly substituted pyrrolidone, doxapram (26-7), that is used as a respiratory stimulant. The synthesis starts with the displacement of chlorine on pyrrolidine (26-1) by the carbanion from diphenylacetonitrile (26-2) to give (26-3) as the product. The quite hindered nitrile is then hydrolyzed to the corresponding carboxylic acid (26-4) by basic hydrolysis. The reaction of acid with thionyl chloride presumably proceeds initially to form the corresponding acid chloride. The close proximity of that group to basic... 

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