Tiffeneau-Demjanov

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 starting material for the Tiffeneau-Demjanov reaction is available by various methods. A common route is the addition of nitromethane to a cyclic ketone—e.g. cyclopentanone 7—followed by a hydrogenation of the nitro group to give the /3-amino alcohol, e.g. 1 ... 

Various side-reactions may be observed with the Demjanov reaction the Tiffeneau-Demjanov reaction usually gives better yields of the ring-enlarged product. 

This reaction has been used to form ring-expanded cyclic ketones, a procedure known as the Tiffeneau-Demjanov reaction 1... 

Thiocarbonates, synthesis of, 17, 3 Thiocyanation of aromatic amines, phenols, and polynuclear hydrocarbons, 3, 6 Thiophenes, synthesis of, 6, 9 Thorpe-Ziegler condensation, 15, 1 31 Tiemann reaction, 3, 9 Tiffeneau-Demjanov reaction, 11, 2 Tin(n) enolates, 46, 1 Tin hydride method to prepare radicals,... 

Treatment of 4,4-dimethyl-2-phenyl-l,3-thiazole-5(4//)-thione with ethyl diazoacetate gives, among other products, ethyl 1,3-thiazine carboxylate (179) (99). The formation of 179 has been rationalized by an acid-catalyzed addition of ethyl diazoacetate to the thiocarbonyl ylide 177 to first give intermediate 178, which undergoes a subsequent ring enlargement reaction via a Tiffeneau-Demjanov rearrangement. 

The formation of diazonium salts from aromatic primary amines by reaction with nitrous acid undoubtedly involves the intermediate formation of V-nitroso compounds. The Demjanov and Tiffeneau-Demjanov ring expansions also involve V-nitroso compounds [2]. Some V-nitroso compounds have been used as sources of free radicals and as blowing agents. 

The stabilization of the intermediate as a carhenium - oxonium ion in the diazotization of P-amino alcohols (Tiffeneau-Demjanov rearrangement) is responsible for the formation of 4-bromo-5,5-dimethylbicyclo[2.1.1]hexane-l-carbaldehyde (30) in the reaction of l-amino-4-bromo-7,7-dimethylbicyclo[2.2.1]heptan-2-ol with nitric acid.96... 

Homoadamantanone is also obtained from the Tiffeneau-Demjanov, 01> 102) and diazomethane 103> 1041 homologations of adamantanone 67> 69 These ring expansions enable easy access to homoadamantane (36) and a variety of 4-mono and 4,5-disubstituted homoadamantanes. Some of this chemistry is summarized in Scheme 12. 

P. A. S. Smith, D. R. Baer, The Demjanov and Tiffeneau-Demjanov Ring Expansions, Org. React. 1960,... 

Fig. 11.19. Ring expansion of cyclic ketones via the Tiffeneau-Demjanov rearrangement. The first step consists of the additions of HCN or nitromethane, respectively, to form either the cyanohydrin or the /i-nitroalcohol, respectively. The vicinal amino alcohol A is formed in the next step by reduction with LiAIII4. The Tiffeneau-Demjanov rearrangement starts after diazotation with the dediazotation.

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