Guanidines nitrosation

The required triamino-4(3H)-pyrimidinone is prepared in three steps starting from guanidine [50-01-1] (14) (26). Condensation with methylcyanoacetate [105-34-0] (15) under basic conditions, followed by nitrosation of the intermediate [56-06-4] (16), gives... 

Triamterene Triamterene, 2,4,7-triamino-6-phenylpteridine (21.5.13), is synthesized in by the following scheme. Reacting guanidine with malonodinitrile gives 2,4,6-triaminopyrimi-dine (21.5.11). This undergoes nitrosation by reacting it with nitric acid, which results in the... 

The best known and most widely used diazoalkane is diazomethane (95 equation 39). Preparative methods for diazomethane involve, in general, the nitrosation of a methylamine derivative (93), followed by cleavage under alkaline conditions. Methylamine derivatives used have included the urethanes, ureas,carboxamides, sulfonamides, guanidines and even the methylamine adducts of unsaturated ketones and sulfones. N-nitroso-N-methyl p-toluenesulfonamide (Diazald, Aldrich) is currently the most commonly used diazomethane precursor. Diazomethane is both toxic and explosive. Although in the past it has been purified by codistillation with ether, it is now usually generated, stored and used as an ether solution without distillation. 

Dihydrothienocoumarins that have analgesic activity without anti-inflammatory activity have been synthesized. Compounds of type (154), with antibacterial, antifungal, and other activities, have been synthesized. Some NN N"-trisubstituted guanidines that contain thiophen rings and have anti-inflammatory properties have been synthesized. " Nitrosation of methapyrilene in vitro has been studied. 

The primary amine (217) underwent the Rathke reaction with the isothiourea (218) to give cimetidine (219). A better yield was obtained with dimethyl cyanodithioimido-carbonate (220) followed by methylamine. Scheme 5.51 [278, 279]. Hydrolysis of cimetidine (219) gives the guanylurea (222) slowly at room temperature but the guanidine (223) at elevated temperature [278]. A first report indicated that nitrosation gave only (224), but this was ammended when (225) was discovered as a minor product. The rate of nitrosation decreases markedly as the pH increases [280, 281]. The solution conformation of cimetidine has been investigated [278]. The MNDO calculations indicate it has a high molecular flexibility with respect... 

The main route for the formation of NOCs is by nitrosation reactions that take place between a nitrosating agent like nitrite (NOi") in an acidic environment, nitrous acid (HNO2), nitrogen oxides (NO2 or NO,c)5 nitrosyl chloride (NOCl), and, on the other hand, a nitrosable agent like some amines, amides, guanidines, urea, and urethane compounds. 

As shown in Scheme 14.1, guanidine hydrochloride [H2NC(NH2)NH2 Cl ] was converted to the free base with sodium ethoxide in ethanol. After the precipitated sodium chloride was removed, the solution was treated with ethyl cyanoacetate.The product of the condensation reaction, on heating (and also on treatment with aqueous base), underwent cychzation to produce 2,4-diamino-6-oxypyrimidine. On nitrosation, followed by reduction (with ammonium sulfide, (NH4)2S), the corresponding 2,4,5-triamino-8-oxopyrimidine resulted and the reaction of the pyrimidine with sodium formate and formic acid yielded guanine (G), indistinguishable from the authentic material. 

Non-volatile nitrosamines are likewise produced by nitrosation of N-alkylsubstituted guanidines and N-alkylsubstituted ureas. N-Methylguanidine, for example, occurs in fresh meat at concentrations of up to lOmg/kg and also arises together with N-nitrosoguanidine by decomposition of creatine in the presence... 

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