Diphenylacetonitrile

Diphenylacetonitrile

Names
Other names 2,2-Diphenylacetonitrile, Dipan, Diphenatrile, Benzhydrylcyanide.
Identifiers
CAS Number	86-29-3
3D model (JSmol)	Interactive image
ChEMBL	ChEMBL3185477
ChemSpider	6576
ECHA InfoCard	100.001.511
EC Number	201-662-5
PubChem CID	6837
UNII	QK4W106TKU
CompTox Dashboard (EPA)	DTXSID4020539
InChI InChI=1S/C14H11N/c15-11-14(12-7-3-1-4-8-12)13-9-5-2-6-10-13/h1-10,14H Key: NEBPTMCRLHKPOB-UHFFFAOYSA-N
SMILES C1=CC=C(C=C1)C(C#N)C2=CC=CC=C2
Properties
Chemical formula	C14H11N
Molar mass	193.24 g/mol
Density	1.1061g/cm3 (estimated)
Melting point	71–73 °C (160–163 °F; 344–346 K)
Boiling point	181 °C (358 °F; 454 K) @ 12 mmHg
Hazards
GHS labelling: [1]
Pictograms
Signal word	Danger
Hazard statements	H301, H315, H319, H335
Precautionary statements	P261, P264, P264+P265, P270, P271, P280, P301+P316, P302+P352, P304+P340, P305+P351+P338, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Diphenylacetonitrile is an organic compound]] with the formula (C₆H₅)₂CHCN. A colorless solid, it has been widely uses in the pharmaceutical industry.

Synthesis

In Hoch's original procedure, phenylacetonitrile was halogenated with molecular bromine to give bromobenzyl cyanide. This species was then reacted with benzene in the presence of aluminium trichloride to afford diphenylacetonitrile. ^[2] This procedure has been optimized over the years. ^{[3] [4]}

An alternative route involves the reaction of bromodiphenylmethane with sodium cyanide under phase transfer conditions: ^[5]

(C₆H₅)₂CHBr + NaCN → (C₆H₅)₂CHCN + NaBr

Applications

• Opioid analgesics: Bezitramide, Dipipanone, Dipyanone, Isomethadol, LAAM, Methadone, ^{[6] [7]} Noracymethadol, Normethadone, Norpipanone, Piritramide, R-4066, R 4837 [59708-47-3], R-5260 [1109-69-9] (25ii): ^[8]
• Psychostimulants: 2-Benzhydrylpiperazine [28217-87-0], ^{[9] [10]} Desoxypipradrol, β-Phenylamphetamine, β-Phenylmethamphetamine, Desoxyhexapradol.
• Antidepressants: McN-4187, ^[11] McN 4612-z ^{[12] [13]} (c.f. JNJ-7925476).
• Antispasmodics: Aminopentamide, ^[14] Buzepide, ^[15] Fenpiverinium, Fenpipramide
  • Urinary incontinence: Darifenacin, Imidafenacin
• Anti-diarrhoeals: Difenoxin, Diphenoxylate, Nufenoxole
• Choleretic and spasmolytic agent: Diisopromine
• Analeptic (respiratory stimulant): Doxapram
• Antiarrhythmic: Isopropanamide ^{[16] [17]}
• Cytochromes P450 inhibitor: Proadifen
• 2,2-DEP [36794-51-1] ^[18] (Hamilton Morris's diphenidine positional isomer drug).

References

1. "Diphenylacetonitrile". PubChem. U.S. National Library of Medicine.
2. Hoch J (1933). "General method for the preparation of di- and triarylacetonitriles". Compt. Rend. 197: 770–772.
3. Robb CM, Schultz EM (1948). Arnold RT, Britain JW (eds.). "Diphenylacetonitrile". Organic Syntheses. 28: 55. doi:10.15227/orgsyn.028.0055.
4. Ginsburg D, Baizer MM (June 1949). "Diphenylacetonitrile". Journal of the American Chemical Society. 71 (6): 2254. Bibcode:1949JAChS..71Q2254G. doi:10.1021/ja01174a512.
5. Kasarekar RB, Sawant SB (January 1987). "Preparation of diphenyl acetonitrile by phase transfer catalysis". Journal of Chemical Technology & Biotechnology. 38 (3): 201–208. Bibcode:1987JCTB...38..201K. doi:10.1002/jctb.280380306.
6. https://bbgate.com/threads/synthesis-of-methadone.193/
7. Golzadeh, R., Mahkam, M., Rezaii, E., Nazmi Miardan, L. (22 December 2021). "Green synthesis of methadone in eutectic solvent". Main Group Chemistry. 20 (4): 463–474. doi:10.3233/MGC-210058.
8. Leysen, J., Tollenaere, J. P., Koch, M. H. J., Laduron, P. (June 1977). "Differentiation of opiate and neuroleptic receptor binding in rat brain". European Journal of Pharmacology. 43 (3): 253–267. doi:10.1016/0014-2999(77)90025-5. PMID   194781.
9. Jongh David Karel De, Akkerman Antonie Marie, Kofman Hendrik,& Vries George De, US2997473 (1961 to Nederlandsche Combinatie voor Chemische Industrie NV).
10. Karel De Jongh David, et al. GB893391 (1962 to Nederlandsche Combinatie voor Chemische Industrie NV).
11. Maryanoff BE, Nortey SO, Gardocki JF (August 1984). "Structure-activity studies on antidepressant 2,2-diarylethylamines". Journal of Medicinal Chemistry. 27 (8): 1067–1071. doi:10.1021/jm00374a022. PMID   6747990.
12. Nielsen, J., Duda, N., Mokler, D., Moore, K. (February 1984). "Self-administration of central stimulants by rats: A comparison of the effects of d-amphetamine, methylphenidate and McNeil 4612". Pharmacology Biochemistry and Behavior. 20 (2): 227–232. doi:10.1016/0091-3057(84)90247-8. ISSN   0091-3057.
13. Maryanoff, B. E., Shank, R. P., Gardocki, J. F. (1986). "McN-5707 and McN-5652-Z". Drugs of the Future. 11 (1): 18. doi:10.1358/dof.1986.011.01.51629. ISSN   0377-8282.
14. Ginsburg D, Baizer MM (August 1957). "Antispasmodics. X. α,α-Diphenyl-γ-amino Amides 1". Journal of the American Chemical Society. 79 (16): 4451–4457. Bibcode:1957JAChS..79.4451M. doi:10.1021/ja01573a056.
15. Janssen PA, Demoen PJ, Jageneau AH, Loomans JL (April 1959). "The influence of heterocyclic ring size of tertiary 2, 2-diphenyl-4-amino-butyramides on parasympatholytic activity". Journal of Medicinal and Pharmaceutical Chemistry. 1 (2): 187–194. doi:10.1021/jm50003a007. PMID   13665290.
16. JANSSEN P, ZIVKOVIC D, DEMOEN P, DE JONGH DK, VAN PROOSDIJ-HARTZEMA EG (1955). "Substituted phenylpropylamines. I. Synthesis and physicochemical properties of basic butyronitriles and butyramides". Archives Internationales de Pharmacodynamie et de Therapie. 103: 82–99. PMID   13259723.
17. Janssen Paul Adriaan Jan & Jongh David Karel De, US2884436 (1959 to Nederlandsche Combinatie voor Chemische Industrie NV).
18. Wallach, J., Kavanagh, P. V., McLaughlin, G., Morris, N., Power, J. D., Elliott, S. P., et al. (May 2015). "Preparation and characterization of the 'research chemical' diphenidine, its pyrrolidine analogue, and their 2,2‐diphenylethyl isomers". Drug Testing and Analysis. 7 (5): 358–367. doi:10.1002/dta.1689.