3,3,-Diphenylcyclobutanamine is a psychostimulant drug which was originally prepared as an antidepressant in the late 1970s. It appears to inhibit the reuptake of serotonin, norepinephrine, and dopamine, and may also induce their release as well. The N-methyl and N,N-dimethyl analogues of the compound are also known and are more potent. All three agents produce locomotor stimulation in animal studies, with the tertiary amine being the strongest.
A number of methods were tried in order to construct the strained four-carbon ring. A synthesis of 3,3-diphenylcyclobutanone
appeared in the literature. The ketone was prepared in low yield by the reaction of diphenylketene with 2 equiv of diazomethane. The latter synthesis, although low yielding, was used and the desired amines were prepared from 3,3-diphenylcyclobutanone.
Diphenylketene is produced by the elimination of hydrogen chloride from diphenylacetyl chloride in the presence of triethylamine.
Preparation of Diphenylketene
- 1 2 3 4 Carnmalm B; Rämsby S; Renyi AL; Ross SB; Ogren SO (January 1978). "Antidepressant agents. 9. 3,3-Diphenylcyclobutylamines, a new class of central stimulants". Journal of Medicinal Chemistry. 21 (1): 78–82. doi:10.1021/jm00199a014. PMID 22757.
- ↑ Wilt, J. W.; Dabek, R. A.; Welzel, K. C. (1972). "Transannular neophyl rearrangement". The Journal of Organic Chemistry. 37 (3): 425–430. doi:10.1021/jo00968a022.
- ↑ Michejda, C. J.; Comnick, R. W. (1975). "Acetolysis of 3,3-disubstituted cyclobutyl tosylates". The Journal of Organic Chemistry. 40 (8): 1046–1050. doi:10.1021/jo00896a010.
- ↑ Edward C. Taylor; Alexander McKillop & George H. Hawks. (1972). Checked by C. J. Michejda, D. D. von Riesen, R. W. Comnick, and Henry E. Baumgarten.. "DIPHENYLKETENE [Ethenone, diphenyl-]". Organic Syntheses. 52: 36. doi:10.15227/orgsyn.052.0036.