A procedure was developed for the synthesis of tetrahydropyrimidine-2,4-diones by desulfurization of 2-thioxo-1,2,3,4-tetrahydropyrimidin-4-ones with oxiranes or 2-haloacetonitriles in polar solvents in the presence of a base.It is known that 2-thioxo-1,2,3,4-tetrahydropyrimidin-4-one derivatives differently react with different alkylating agents. In most cases, the reaction gives the corresponding 2-alkylsulfanylpyrimidin-6(1H)-ones or 2-alkylsulfanyl-1-alkylpyrimidin-4(1H)-ones, while 2-chloroacetic acid reacts with 2-thioxo-1,2,3,4-tetrahydropyrimidin-4-ones in an aqueous solution to afford tetrahydropyrimidine-2,4-diones.We found that 2-methyloxirane and 2-iodoacetonitrile are also capable of effecting desulfurization of 2-thioxo-1,2,3,4-tetrahydropyrimidin-4-one derivatives with formation of 1,2,3,4-tetrahydropyrimidine-2,4-diones (Scheme 1). The reactions were performed using the following base-solvent systems (which are typically used for alkylation of 2-thioxo-1,2,3,4-tetrahydropyrimidin-4-ones): K 2 CO 3 -DMFA, NaH-DMFA, NaOMe-MeOH, KOH-EtOH, and NaOH-H 2 O. The yield of the resulting pyrimidine-2,4-dione derivatives was quantitative, regardless of the base used.While studying desulfurization of 2-thioxo-1,2,3,4-tetrahydropyrimidin-4-ones Ia-Ie we showed that 2-phenyloxirane and 2-ethyloxirane also equally effective in this reaction, and the corresponding 1,2,3,4-tetrahydropyrimidine-2,4-diones IIa-IIe were formed in quantitative yield. Presumably, the reason is that the examined oxirane derivatives possess an endocyclic methylene group which is not shielded with respect to nucleophilic attack. Both protic polar solvents (H 2 O, MeOH, EtOH) and aprotic dimethylformamide ensured quantitative formation of pyrimidinediones IIa-IIe. This suggests that the solvent does not participate in the reaction with initially formed 2-[(2-hydroxyalkyl)sulfanyl]pyrimidinone and that oxirane acts as source of oxygen.Desulfurization of compounds Ia-Ie with 2-iodoacetonitrile (as well as with 2-bromo-and 2-chloroacetonitrile) resulted in quantitative formation of pyrimidinediones IIa-IIe only when the reaction was carried out in an alcoholic medium. The reaction in DMF in the presence of K 2 CO 3 was accompanied by strong tarring. Treatment of Ia-Ie with 2-iodoacetonitrile in aqueous sodium hydroxide afforded compounds IIa-IIe in a poor yield, and the conversion of initial 2-thioxopyrimidinones was not complete. These data indicate that the process should be performed in a protic solvent which is likely to promote cleavage of the initially formed 2-(cyanomethylsulfanyl) derivative. The low yield of pyrimidine-2,4-diones in the reaction in water may be due to heterogeneous conditions and concurrent hydrolysis of 2-iodoacetonitrile.It should be noted that the maximal yield of compounds II in the reactions with both substituted oxiranes and 2-haloacetonitriles was observed only when the amount of base was equal to or greater than equimolar. Reduction of the amount of base leads to proportional decrease in the conversion (accor...

We describe here a new and efficient method for synthesis of N-(3-phenyl[2.2.1]bicyclohept-2-yl)-N-ethylamine hydrochloride (Fencamfamine), based on the reduction of trans-5-nitro-6-phenylbicyclo[2.2.1]hept-2-ene with Raney alloy mixed with aqueous NaOH and tetrahydrofuran followed by N-alkylation of the resulting product with 95% ethanol in the presence of skeletal nickel.

Pyrimidine derivatives R 0510Desulfurization of 2-Thioxo-1,2,3,4-tetrahydropyrimidin-4-ones with Oxiranes and 2-Haloacetonitriles. -2-Substituted oxiranes and 2-haloacetonitriles are capable to effect desulfurization of 2-thioxotetrahydropyrimidone derivatives (I) furnishing the corresponding diones (II) in quantitative yields. -(NOVAKOV, I. A.; ORLINSON, B. S.; NAVROTSKII, M. B.; Russ. J. Org. Chem. 41 (2005) 4, 607-609; Volgograd State Tech. Univ., Volgograd 400131, Russia; Eng.) -A. Forchert 43-173

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