Demjanov reaction

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 ... 

The original Demjanov reaction is the conversion of an aminomethyl-cycloalkane into a cycloalkanol consisting of a carbocyclic ring that is expanded by one carbon center e.g. the reaction of aminomethylcyclohexane 8 with nitrous acid leads to formation of cycloheptanol 9 ... 

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,... 

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. 

Aminomethylcarbinols yield ketones when treated with nitrous acid. This reaction has been used synthetically to form ring-expanded cyclic ketones, a procedure known as the Tiffeneau-Demjanov reaction The diazotization procedure generates the same type of /3-hydroxycarbonium ion that is formed in the... 

In protic solvents, at least, the reaction proceeds via essentially the same intermediate that is involved in the Tiffenau-Demjanov reaction. Since the product is also a ketone, subsequent addition of diazomethane can lead to higher homologs. The best yields are obtained when the starting ketone is more reactive than the product. For this reason, strained ketones often work well in this reaction. Higher diazoalkanes can also be employed. The reaction has been found to be accelerated by alcoholic solvents. This effect probably involves the hydroxyl group acting as a... 

---