Amino alcohols diazotization

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 ... 

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. 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.

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. 

Tiffeneau-Demjanov ring expansion. Rearrangement of (i-amino alcohols on diazotization with nitrous acid to give ring-expanded carbonyl compounds. 

Diazotization. 2-Amino alcohols an to epoxides. The method has been applied 1 lene oxides from threonine. 

Rearrangement of (3-amino alcohols upon diazotization with nitrous acid to give carbonyl compounds. Cyclic alcohols yield ring expanded or contracted products ... 

Diazotization of alkylamines represents the most direct conceivable route to diazoalkanes (2). However, isolation of non-stabilized diazoalkanes by this strategy is not feasible they fail to survive the strongly acidic conditions of the synthesis. If diazotization is performed on 1,2-amino alcohols with sodium nitrite at low pH, Tiffeneau-Demjanov rearrangement (TDR) [64, 65] occurs through a cationic (vs zwitterionic) intermediate to give a rearranged ketone (3). 

Preparation of 2-Hydroxy-4,4 -Dicyanostilbene 10 grams of 2-amino-4,4 -dicyanostilbene thus prepared were dissolved in 400 cc of boiling glacial acetic acid and 200 cc of dilute sulfuric acid added the solution was suddenly chilled and diazotized over one and a half hours at 5° to 10°C with sodium nitrate (3.0 grams/15 cc H O). The diazonium salt solution was decomposed by boiling for 15 minutes with 600 cc of 55% aqueous sulfuric acid solution the solution was diluted, cooled and filtered. The residue crystallized from ethyl alcohol as lemon yellow prismatic needles, MP 296°C. 

As shown in Scheme 199, the 5-aminopyrimidine stmcture may be also incorporated into a more complex bicyclic system. Thus, diazotization of 3-amino-4-oxo-4//-pyrimido[ 1,23 lpyndazincs 1198 followed by treatment with 50% aqueous tetrafluoroboric acid results in precipitation of salts 1199. When heated with alcohols, nucleophilic attack on the carbonyl group opens the pyrimidine ring. The obtained species 1200 assume conformation 1201 that is more suitable for bond formation between the opposite charged nitrogen atoms. Alkyl l-(pyridazin-3-yl)-l//-l,2,3-triazole-4-carboxylates 1202 are obtained in 31-66% yield <2002ARK(viii)143>. 

Dinitroetbylbenzene, mp 59 5° It was prepd in a similar manner to the 2,3 derivative above 2,6 Dinitroetbylbenzene, mp 57-5°. It was prepd in a similar manner to the 2,3 derivative above 3.5 Dinitroethylbenzene, mp 41°. It may be prepd by diazotization of 3,5"dinitro-4-aminO-I-ethyl-benzene followed by heating with alcohol... 

Fluorination of alkenes. The reagent adds in the Markownikofl fashion to alkenes to yield alkyl fluorides (35-90% yield). It converts secondary and tertiary alcohols into the corresponding alkyl fluorides. In situ diazotization followed by dediazotization converts a-amino acids into a-fluorocarboxylic acids (38-98% yield). The reagent converts acid chlorides and anhydrides into acid fluorides. ... 

The replacement of an amino group by a mercapto group on an aromatic nucleus is effected by treating the diazotized amine with potassium ethyl xanthate and hydrolyzing the resulting aryl ethyl xanthate (Leuckart). Yields of 40-80% are reported for thiophenols containing methyl, halo, and methoxyl groups. Potassium ethyl xanthate is readily prepared from alcoholic potassium hydroxide and carbon disulfide. ... 

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