Diphenylacetic acid

Place 125 ml. of glacial acetic acid, 7 -5 g. of purifled red phosphorus (Section II,50,d) and 2 5 g. of iodine in a 500 ml, round-bottomed flask fitted with a reflux condenser. Allow the mixture to stand for 15-20 minutes with occasional shaking until aU the iodine has reacted, then add 2 5 ml. of water and 50 g, of benzilic acid (Section IV,127). Boil the mixture under reflux for 3 hours, and filter the hot mixture at the pump through a sintered glass funnel to remove the excess of red phosphorus. Pour the hot filtrate into a cold, weU-stirred solution of 12 g. of sodium bisulphite in 500 ml, of water the latter should be acid to litmus, pro duced, if necessary, by passing sulphur dioxide through the solution. This procedure removes the excess of iodine and precipitates the diphenyl-acetic acid as a fine white or pale yellow powder. Filter the solid with suction and dry in the air upon filter paper. The yield is 45 g., m.p. 

142-144°. Upon recrystallisation from about 250 ml. of 60 per cent, alcohol, crystalline diphenylacetic acid, m.p. 144-145° (1), is obtained. 

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Benzilic acid melts at 149-150°, i.e., very close to that of diphenylacetic acid. The completeness of the reduction can easily be tested by treating a little of the product with concentrated sulphuric acid if even a trace of benzilic acid remains, the sulphuric acid will have a rod colour. 

Tetraphenylethane (2). A solution of diphenylacetic acid 1 (2f fS g, O.f mol) In OMF was electrolyzed for 17 h and the voltage was increased from f 20 to 220 V dunng electrotysts. The reaction mixture was poured into water and extracted with EtjO. The extract was filtered, washed and the solvent evaporated. Recrystallization from CHCI3 gave 4 g of 2 (24%), mp 207-208 C. 

Esters of diphenylacetic acids with derivatives of ethanol-amine show mainly the antispasmodic component of the atropine complex of biologic activities. As such they find use in treatment of the resolution of various spastic conditions such as, for example, gastrointestinal spasms. The prototype in this series, adiphenine (47), is obtained by treatment of diphenyl acetyl chloride with diethylaminoethanol. A somewhat more complex basic side chain is accessible by an interesting rearrangement. Reductive amination of furfural (42) results in reduction of the heterocyclic ring as well and formation of the aminomethyltetrahydro-furan (43). Treatment of this ether with hydrogen bromide in acetic acid leads to the hydroxypiperidine (45), possibly by the intermediacy of a carbonium ion such as 44. Acylation of the alcohol with diphenylacetyl chloride gives piperidolate (46). ... 

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

Diphenylacetic acid. The reduction of benzilic acid with red phosphorus and a little iodine in 98 per cent, acetic acid solution yields diphenylacetic acid ... 

Butyllithium in hexanes (2.5 M) is purchased from Aldrich Chemical Company, Inc., and titrated using diphenylacetic acid.2... 

H-12,3,6a-Ethanylylidene-7,9-methanonaphth[2,3-b]azocine-4,8,9,ll,lla(lH,7H)-pentol, l-Ethyldecahydro-6,10,13-trimethoxy-3-(methoxymethyl)-, lla-Acetate 8-Benzoate 2-Hydroxy-2,2-diphenylacetic Acid (2-Hydro xyethyl)diethylamine 2-Hydro xytriethylamine 2-Isocyanatopropane 2-ME... 

The cell is suitable for the manufacture of (i) metal alkoxides, (ii) thiolates, (iii) carboxylates, (iv) hydroxides, (v) organometallics and chemicals such as diphenylacetic acid, (vi) ortho- and para-trifluoromethyl-benzoic acid, (vii) aryl-... 

The submitters used butyllithium in hexane available from Janssen Chimica and standardized before use by titration against a solution of benzylic alcohol in toluene and cuproine (2,2 -biquinoline). The checkers used butyllithium (1.6 M in hexane) available from Aldrich Chemical Company, Inc., which was standardized before use by titration with diphenylacetic acid in THF. 

Superior grade diphenylacetic acid, m.p. 147-148° (Mat-heson Coleman and Bell) was used without further purification. 

A variant for the determination of the organoiithium compounds avoiding the double titration is based on the use of diphenylacetic acid in THF solution, to which the solution... 

Whereas 1,1,1-triphenylethane 551 gave only 2% of triphenylacetic acid 552 after treatment with lithium and a substoichiometric amount (50%) of biphenyl, followed by carbonation and acidic hydrolysis, the same process carried out starting from 1,1,1,2-tetraphenyl ethane 553 or 1,1,2,2-tetraphenylethane 554 gave tri- 552 or diphenylacetic acid 555, respectively, with excellent yields (Scheme 148). ... 

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... 

In a i-l. round-bottom flask are placed 250 cc. of glacial acetic acid, 15 g. of red phosphorus and 5 g. of iodine. The mixture is allowed to stand for fifteen to twenty minutes until the iodine has reacted, and then 5 cc. of water and 100 g. of benzilic acid are added. A reflux condenser is attached and the mixture is boiled continuously for at least two and a half hours. After the reaction is complete, the hot mixture is filtered with suction to remove the excess red phosphorus (Note 2). The hot filtrate is slowly poured into a cold, well-stirred, filtered solution of 20-25 g- °f sodium bisulfite in 1 1. of water (Note 3). This procedure removes the excess iodine and precipitates the diphenylacetic acid as a fine white or slightly yellow powder (Note 4). The product is filtered with suction, washed with cold water and dried thoroughly on filter paper. The yield is 88-90 g. (94-97 per cent of the theoretical amount) of a solid melting at 141-1440 (Note 5). If a crystalline product is desired, the acid is dissolved in about 500 cc. of hot 50 per cent alcohol and then cooled. The melting point after recrystallization is 144-1450. 

Some samples of sodium bisulfite caused part of the diphenylacetic acid to dissolve. This can always be avoided if, after the solution of sodium bisulfite is prepared, a current of sulfur dioxide is passed in, until the solution is acid to litmus. 

The melting points of benzilic acid and diphenylacetic acid lie very close together. However, it is very easy to test for complete reduction by treating a little of the product with cold concentrated sulfuric acid. If even a trace of benzilic acid remains the sulfuric acid will turn red. 

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... 

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