Amino alcohols reaction with nitrous acid

When a cyclic /3-amino alcohol—e.g. 1—is treated with nitrous acid, a deamination reaction can take place, to give a carbenium ion species 2, which in turn can undergo a rearrangement and subsequent loss of a proton to yield a ring-enlarged cyclic ketone 3. This reaction is called the Tiffeneau-Demjanov reactionit is of wider scope than the original Demjanov reaction ... 

The reaction of nitrous acid with the amino group of the /3-amino alcohol—e.g. 1-aminomethyl-cyclopentanol 1—leads to formation of the nitrosamine 4, from which, through protonation and subsequent loss of water, a diazonium ion species 5 is formed " —similar to a diazotization reaction ... 

Treatment of a primary aliphatic amine with nitrous acid or its equivalent produces a diazonium Ion which results in the formation of a variety of products through solvent displacement, elimination and solvolysis with 1,2-shift and concurrent elimination of nitrogen. The stereochemistry of the deamination-substitution reaction of various secondary amines was investigated as early as 1950, when an Swl-type displacement was suggested. Thus, the process can hardly be utilized for the preparation of alcohols except in cases where additional factors controlling the reaction course exist. Deamination-substitution of a-amino acids can be utilized for the preparation of chiral alcohols. 

In the pinacol-pinacolone rearrangement a 1,2-diol rearranges to give a carbonyl group that is adjacent to a quaternary carbon. There are many variations of this reaction for example, the semipinacol rearrangement, in which a (P-amino alcohol is treated with nitrous acid. This reaction may be modified so that a ring expansion takes place, in which case it is called the Tiffeneu-Demyanov ring expansion. 

There are, of course, many amino acids that can be used to prepare new amino acids. One is p-arginine (i.23f,),which reacted with nitrous acid (HONO, generated in situ by reaction with sodium nitrite and acid) to convert one amino group to an alcohol moiety. The final product was 2-hydroxy-4-aminobutanoic acid (7.232). 36... 

The action of nitrous acid on the benzodiazepine A -oxide 38 gives the nitrosoamino derivative 39,234 which reacts with alcohols, ethanethiol and various amino compounds, such as hydrazines and guanidine, by replacement of the methyl(nitroso)amino group.235 Reaction with aziridine affords the aziridinyl compound 40f or the 2-(aziridin-l-yl)ethylainino derivative 40g, depending on the conditions. 

Nitrous acid deamination (aqueous acetic acid) of 3)5-amino-5a-cholestane gives mainly substitution derivatives with retention of configuration. The reaction is, however, accompanied by elimination. 3a-Amino-cholestane gives the 3a-derivative, along with large amounts of elimination products. 20a-Amino-5a-pregnanes give substitution derivatives (especially alcohols) with... 

All these early results were consistent with the Dn + An mechanism. Indeed, Roberts and Mazur (1951a) found in a comparative study that reactions of aqueous nitrous acid with four substituted l-amino-but-2-enes and 3-amino-but-l-enes yielded the same mixtures of substituted butenols (methylated allylic alcohols) as those of silver ion catalyzed aqueous solvolyses of the corresponding chlorides. This fits the hypothesis that both types of reaction result in the formation of the same carbocation, independent of the route from the amine or from the chloride. This rate-determining part of the reaction is followed by fast product-determining steps. 

Amino alcohols rearrange in the presence of nitrous acid to give ketones. The intermediate is an aliphatic diazonium salt, and the reactions are concerted and stereo-electronically controlled, with the migration of the group trans-anti to the departing nitrogen. 

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