P-Toluamide

A derivative of benzylhydrazine, procarbazine (8), exhibits antineoplastic activity. In an interesting insertion-type sequence, reaction of the p-toluamide (5) with ethyl azodicarboxylate leads directly to the substituted hydrazine (6). It is not unlikely that the first mole of the diazo compound... 

Figure 6. Photographs of crystals of benzamide (a) pure (b)-(d) grown in the presence of increasing amounts (from bottorrf to top) of (b) benzoic acid (c) o-toluamid, (d) p-toluamid. The crystals shown in this photograph (and all those following) varied in size from about 0.1 to 5 mm.

A series of trisubstituted guanidines has been prepared by Drewry et al.19 a-Bromo-p-toluamide was converted to the azide by reaction with sodium... 

Thiirene-1-oxides 128 furnished oxazoles 129 with two bulky alkyl substituents at vicinal positions by treatment with trifluoroacetic anhydride and p-toluamide <02CL314>. 

Synonym. Ibenzmethyzin A-Isopropyl-a-(2-methylhydrazino)-p-toluamide C12H19N3O-22I.3 CAS—671-16-9... 

SYNS IBENZMETHYZINE HYDROCHLORIDE IBENZMETHYZIN HYDROCHLORIDE IBZ l-(p-ISOPROPYLCARBAMOYLBENZYL)-2-METHYLHYDRA-ZINE HYDROCHLORIDE 2-(p-(ISOPROPYLCAR-BAMOYL)BENZYL)-l -METHYLHYDRAZINE HYDROCHLORIDE N-ISOPROPYL-p-(2-METHYLHY-DRAZINOMETHYL)BENZAMIDEHYDROCHLORIDE N-ISOPROPYL-a-(2-METHYLHYDR. ZINO)-p-TOLUAMIDE HYDROCHLORIDE MATULANE ... 

Procarbazine Hydrochloride, USP. Procarbazine hydrochloride, Malulane. MIH. NSC-77213, N-isopropyl-o-(2-methylhydrazine)-p-toluamide. is prepared from N-iso-propyl-/>-toluamide in a process involving condensation with diethyl azodicarboxylate. methylation with methyl itxlide and base, and acid hydrolysis. Although soluble in water, it is unstable in solution. Capsules containing the equivalent of SO mg of procarbazine as its hydrochloride ore supplied. 

Kelly MG, O Gara RW, Yancey ST, et al. 1968. Comparative carcinogenicity of 7V-isopropyl- -(2-methylliydrazino)-p-toluamide HCI procarbazine hydrochloride), its degradation products, other hydrazines, and isonicotinic acid hydrazide. J Nat Cancer Inst 42 337-342. 

Moloney SJ, Wiebkin P, Cummings SW, et al. Metabolic activation of the terminal N-methyl group of N-isopropyl-a-(2-methylhydrazino)-p-toluamide hydrochloride (procarbazine). Carcinogenesis 1985 6 397-401. 

Brule G, Schlumbeiger JR, Griscelli C N-isopro yl-a-(2-methylhydrazino)-p-toluamide, hydrochloride (NSC-77213) in treatment of solid tumors Cancer Chemo ier Rep 965) 44,31-8. 

Samuels ML, Leary WV, Alexanian R, Howe CD, Frei E. Clinical trials with N-isoprofyl-a-(2-melhylhydrazino)-p-toluamide hydrochloride in malignant lymphoma and other dii mi-nated neoplasia. Ccffjcer(1967) 20. 1187-94. 

De Vita VT, Hahn MA, Oliverio VT, Monoamine oxidase inhibition by a new carcinostatic agent. N-isopropyl-a-(2-methylhydrazino)-p-toluamide (MIH). Proc Soc Exp Biol Med (1965) 120, 561-5. 

---