Nitrous deamination

Bis(trimethylsilyl)methanol is obtained when BSMA is subjected to the usual conditions of a nitrous deamination reaction.318 Neither starting material nor a monosilylated compound are recovered. 

Ou, Z., Chen, Z., Jiang, O. Demjanov rearrangement on synthetic zeolites. Kexue Tongbao (Foreign Language Edition) 1987, 32, 462-464. Tchoubar, B. Extension of alicylic rings of 1-(aminomethyl)cycloalkanols by nitrous deamination. II. Nitrous deamination of (aminomethyl)cycloalkanols. Bull. soc. chim. France 1949,164-169. 

T. Posternak, Studies on cyclitols XIV. Nitrous deamination of aminocyclitols. Synthesis of d, 1-vibumitol and new total synthesis of meso-inositol, Helv. Chim. Acta, 33 (1950) 1597-1604. 

As shown in section 2.1.1 and figure 15, (-t-)-muricatacin 19 has been synthesized in 4 steps and 48 % overall yield from a very inexpensive starting material, L-glutamic acid. The key steps of the synthesis are a nitrous deamination of an a-amino acid with retention of the configuration of the stereogenic centre, and a very diastereoselective reduction of a-butyrolactonic ketone 18 with L-Selectride . The use of D-glutamic acid allowed the preparation of (-)-muricatacin 19 as well. 

The pyrolyses of JV-nitroso-A-acetylamines also probably generate ion pairs in the usual non-polar reaction media, e.g. />-cymene, for little rearrangement is reported Diazoalkanes, formed by elimination from diazohydroxides, are unlikely intermediates in nitrous deamination, for neither ethylamine nor isobutylamine gives labelled products when the reaction is conducted in deuterated media these observations also exclude 7r-complex intermediates -... 

Table 1. Rearranged products from nitrous deamination of alkylamines " .

Products of nitrous deamination of allylamines in acetic acid indicate that the mesomeric ion found in 5 1 for analogous halides is not generated. Thus primary dcohols are formed rather than the secondary or tertiary isomers expected fron fiicile double-bond rearrangement. Apparently, the hot ion has its p orbital at C(i) orientated at a dihedral angle > 0°, and probably 90° with the n orbital of the double bond, and solvolysis is more rapid than alignment to ensure overlap. In more aqueous media such alignment, permitted by partial or entire solvation of the carbonium centre, is allowed and products typical of 5n1 are obtained . 

Figure 22 5 shows what happens when a typical primary alkylamine reacts with nitrous acid Because nitrogen free products result from the formation and decomposition of diazonium ions these reactions are often referred to as deamination reactions Alkyl... 

Goldberg and Wydler have shown that the 17a-ketone is not the only product of the Tiffeneau ring enlargement sequence. Careful examination of the products derived from nitrous acid deamination of 17a-aminomethyl-5a-androstane-3/l,17j6-diol 3-acetate (91) showed the presence of a minor amount of isomeric D-homo-17-one (98). 

Treatment with nitrous acid caused deamination of the NI-NH2 group of the l,5-diamino-l,2,4-triazolo[l,5-c]quinazolinium bromide 170, leaving the C5-NH2 group intact to furnish 171 (73TL1643) (Scheme 66). 

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 Deamination of Adenosine 20 g of adenosine are dissolved in one liter of water by warming, and after cooling to room temperature 120 g of barium nitrite (monohydrate) are added to the solution. Under stirring there is added in time intervals of one hour 160 cc of 2N sulfuric acid after each time interval. After the third addition, the reaction mass is allowed to stand for 3 hours at room temperature. The solution is then tested for barium, and if some barium is still present a slight excess of sulfuric acid is added. 300 cc of methanol is then added. In order to drive off the excess of nitrous acid, CO is conducted... 

The nitrosation of amides may also be carried out with nitrosyl chloride.2 Related methods of deamination of aliphatic amines are the triazene3 and nitrous acid methods4... 

Dimtrogen tetroxide is the most versatile of the nitrosating reagents and, in addition, it is readily available. The nitro-soamide method of deamination gives far superior yields and much less skeletal isomerization than the nitrous acid method (which is essentially limited to aqueous media), and it leads to a greater retention of optical activity than the triazene method3... 

In 1967, Heidelberger, Stacey et al. reported the purification, some structural features, and the chemical modification of the capsular polysaccharide from Pneumococcus Type I. Difficulties of direct hydrolysis of the polysaccharide were overcome and it was possible to identify some of the fragments in the hy-drolyzate. At least six products resulted from nitrous acid deamination. Two were disaccharides, which were identified, and sequences of linked sugar units were proposed. As modification of the polysaccharide decreased the amounts of antibody precipitated by anti-pneumococcal Type I sera, the importance of the unmodified structural features in contributing to the specificity of the polysaccharide was indicated. 

Protoadamantanone has been prepared by the nitrous acid deamination of 2-amino-l-adamantanol (77%), by aprotic diazo-tization of endo-7-aminomethylbicyclo[3.3.1]nonan-3-one in benzene with an equivalent amount of acetic acid (67%), and by thermolysis of 1-adamantyl hypohalites followed by base-promoted cyclization of the resulting halo ketones (32-37%)." In spite of low and erratic yields, the last reaction sequence has provided the most convenient route to the protoadamantanes, since the other two approaches require lengthy syntheses of the starting materials. 

More-specific methods are available for identifying and quantitating the typical, amino sugar component of heparin (and some heparan sulfate species), namely, 2-deoxy-2-sulfoamino-D-glucose. Most of these methods are based on conversion of these residues into 2,5-anhydro-D-mannose by deamination with nitrous acid (see Section VIII,2). The 2,5-anhydro-D-mannose residues may be determined either colorimetrically,52-54 or fluorimetrically.55... 

Both positional linkages (uronic acid to hexosamine and hexosamine to uronic acid) were established as being (1 — 4) by structural analysis of the previously mentioned (see Section IV), crystalline disaccharides containing D-glucuronic acid, isolated from an acid hydrolyzate of carboxyl-reduced heparin.128-129 Further evidence was obtained from the structure of the D-glucuronic acid-containing counterpart of disaccharides 6 and 8, obtained as minor products from pig-mucosal heparin following nitrous acid deamination,1110 136-138 and acid hydrolysis followed by N-acetylation,130 respectively. 

Scheme 2. — Nitrous Acid Deamination of 2-Amino-2-deoxy-D-glucose and Its Glycosides.

The scope of the deamination reaction was extended to the characterization of heparin segments containing 2-acetamido-2-deoxy-D-glucosyl residues by removing (by hydrazinolysis) the N-acetyl groups and cleaving with nitrous acid (at pH 4) the otherwise resistant segments.113,232... 

Treatment of cordycepin with nitrous acid, and subsequent hydrolysis of the deaminated product, yields hypoxanthine, indicating that in the adenine moiety the primary amino group is free and the glycosidic linkage involves C7 or C9. The close similarity between the ultraviolet absorption spectrum of cordycepin and those of 9-methyladenine and adenosine63 (9-/3-J>-ribofuranosyladenineMa) favors the latter possibility. The complete stereoisomeric description of cordycepin (XXVIII), formulation of which... 

This means that the ionization and rearrangement need not be concerted and that symmetrical protonated ethylene can not be a major intermediate in the reaction. A similar experiment with isobutylamine and nitrous acid in heavy water gave products that contained no carbon-deuterium bonds. Since it is known that the -complex formed from isobutylene and acid is in rapid equilibrium with protons from the solvent, none of this can be formed in the nitrous acid induced deamination. This in turn makes it probable that the transition state for the hydrogen migration is of the sigma rather than the -bonded type.261... 

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