CHO CHO CHO 21-10 Nitrosation of Amines fPhNeaemy8caYepao026eR CN-00 d mewhether the saocamaeunsaebeaueute gsemeahaeatofmethyrN-nitrosamidesgves mn匹，l--和◆+k0+时 RR-米细之R-巴发胎k 7 7 The Mannich Reaction can be used to synthesize the framework of the natural product, retronecine: 21-10 Nitrosation of Amines Amines react with nitrous acid through nucleophilic attack on the nitrosyl cation, NO+. The remaining course of the reaction depends on whether the amine nitrogen bears zero, one or two hydrogens. Tertiary N-nitrosoammonium salts are stable only at low temperatures and decompose upon heating to a mixture of products. Secondary N-nitrosammonium salts are simply deprotonated to furnish the relatively stable N-nitrosamines as major products. Primary N-nitrosammonium salts are unstable because of the remaining proton on the nitrogen: Base treatment of N-methyl-N-nitrosamides gives diazomethane. Treatment of N-methyl-N-nitrosamides with an aqueous base leads to the formation of diazomethane, CH2N2, which is used in the synthesis of methyl esters from carboxylic acids. Because of its toxicity and sensitivity in the gaseous state, it is usually generated in dilute ether solution and immediately allowed to react with the acid