Rearrangements, Demjanov

In the case of the Tiffeneau-Demjanov rearrangement, the starting material is an aminomethylalkanol 5 thus after formation of the diazoalkane 6, the neighboring alcohol serves as an electron source to provide an electron push to satisfy the formed cation. In this sense, the Tiffeneau-Demjanov rearrangement resembles a pinacolic deamination process and provides a ketone 7. 

In this review, both cyclic and acyclic work will be considered with focus predominantly on cyclic work. 

Demjanov described the rearrangement initially in 1901, but the reaction was not recognized until 1903 when he reported the rearrangement of 

Tiffeneau and co-workers reported their discovery of the reaction in 1937 for the ring expansion of hydroxy-cyclohexylmethyl amine 10 to form cycloheptanone 11. This reaction also has been applied to numerous cases in which a ring expanded ketone was formed. 

The mechanism for the Demjanov reaction is a well accepted mechanism. The formation of the diazonium occurs as outlined. Reaction of the amine 1 with activated NOX 12 (X is thought to be ONO) delivers the A-nitroso compound 13, which undergoes rearrangement to provide hydroxyl-diazo material 14. Protonation of 14 and loss of water provides the diazonium, which suffers loss of N2 to provide cation 16. Carbocation 16 then undergoes rearrangement to provide 3, which traps a nucleophile (typically water sometimes nucleophilic co-solvents or acid counterions like acetate) and provides the alcohol 4. 

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Demjanov rearrangement org chem A structural rearrangement that accompanies treatment of certain primary aliphatic amines with nitrous acid the amine will undergo a ring contraction or expansion. dem ya-nof re-3 ran -m3nt) denaturant chem An inert, bad-tasting, or poisonous chemical substance added to a product such as ethyl alcohol to make it unfit for human consumption. de na-chs rsnt ... 

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 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... 

Fig. 14.21. Ring expansion of cyclic ketones via the Tiffe-neau-Demjanov rearrangement. The first step consists of the additions of HCN or nitromethane, respectively, to form either the cyanohydrin or the /J-nitroalcohol, respectively. The vicinal amino alcohol A is formed in the next step by reduction with LiAlH4. TheTiffeneau-Demjanov rearrangement starts after diazota-tion with the dediazotation.

Semipinacol rearrangements of diazonium salts derived from 2-aminb alcohols are sometimes called Tlffeneau-Demjanov rearrangements. 

Selectivity in rearrangement reactions is affected by the electronic nature of both the group that migrates and the group that is left behind. But there is more Stereochemistry is important too. The outcome of diazotization and semipinacol rearrangement (Tiffeneau-Demjanov rearrangement) of this amino-alcohol depends entirely on the diaster eoisomer you start with. There are four diastereoisomers, and we have drawn each one in the only conformation it can reasonably adopt, with the f-butyl group equatorial. 

Similar results were obtained on application of the related Tiffeneau-Demjanov reaction. This semipi-nacol-type reaction, an extension of the Demjanov rearrangement, involves the rearrangement of a diazonium ion (25 Scheme 7), which is generated by the diazotization of the corresponding amino alcohol (24).The amino alcohol is obtained from the ketone by reduction of a nitrome ane adduct (23a), cyanohydrin (23b) or trimethylsilyl cyanohydrin (23c). This procedure allows for a controlled addition-rearrangement sequence in cases where the use of diazomethane is complicated by the further reaction of the product ketone. 

Table 1 Ring Expnasion of Bridged Bicyclic Ketones with Diazoalkanes or Tiffeneau-Demjanov Rearrangement... 

The conversion of a bicyclo[2.2.1]octenone derivative to the corresponding bicyclo[3.3.0]octenone, a common intermediate in the total synthesis of several iridoid monoterpenes, was achieved by N.C. Chang et al. The target was obtained by sequential application of the Corey-Chaykovsky epoxidation, Demjanov rearrangement and a photochemical [1,3]-acyl shift. 

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