Introduction of the Amino Group

In Chapter 7, the reduction of the nitro group to produce aromatic amines was discussed in some detail. This is the most important method for synthesizing amines. 

There is a series of related reactions in which the common theme is a 

Other groups such as nitroso, hydroxylamine, azo, azoxy and hydrazo may also be reduced by similar means, though with varying degrees of difficulty, but their use is rather limited. 

A nitrene is a species in which the nitrogen has only a sextet of electrons cf. carbene, p.54)  

The individual named reactions are summarized in Table 8.1, but two examples are particularly useful and are discussed in detail. 

Much the tiiechanistic sttidy invoiveci aliphatic amides and evidence ior Ihe concerted mechanism includes the fact that there is complete retention of stereochemistry in tiie migratin aliphatic group. 

1 the rearrangement. The isocyanate reacts with water and the resulting unstable carbamic acid spontaneously decarboxylates to the amine. 

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The final step can involve introduction of the amino group or of the carbonyl group. o-Nitrobenzyl aldehydes and ketones are useful intermediates which undergo cyclization and aromatization upon reduction. The carbonyl group can also be introduced by oxidation of alcohols or alkenes or by ozonolysis. There are also examples of preparing indoles from o-aminophcnyl-acetonitriles by partial reduction of the cyano group. 

Synthesis of these prolylamide mimics is based on the Peterson olefination between tert-butyl a-fluoro-a-trimethylsilyl acetate and a protected hydroxypentanone. Further introduction of the amino group is rather difficult. This step has been accomplished through conversion of the ester into aldehyde, followed by the formation of the silylated aldimine with LiHMDS, and then the addition of methyl lithium (Figure 7.23). ... 

A method to prepare 2a based on the work of a related analog [4] was employed for the first mulh-kilogram campaign. In this approach, 2a was prepared from lactam 5, which is derived from an optically enriched P-hydroxy acid. This method requires introduction of the amino group as an 0-benzylhydroxylamine, which we hoped would sufficiently protect the amino group of 2b during amide formation with triazole 3. 

The second route to glycosyl amine involves the introduction of the amino group at the reducing end of an unprotected carbohydrate in the presence of saturated ammonium bicarbonate (96) (Fig. 12). 

A new route to bromopyrroles was developed. It depends on addition of HBr to A-protected y-aminoynones. When applied to alkynyl ketones, 2-aryl or 2-alkyl 4-bromopyrroles are formed. 2-Alkyl or 2-aryl 3-bromopyrroles can be obtained from acetals of V-aminoynals. The ketones are made from A -protected propargylamines by ( -acylation. The acetals are made from 3,3-diethoxypropyne by addition to an aldehyde followed by introduction of the amino group by reaction with phthalimide under Mitsunobu conditions. <95S276>... 

The introduction of the amino group was performed by reaction of tetrabenzylglucose with benzylamine. The resulting glycosylamine25 was then treated with allylmagnesium bromide in order to introduce stereoselectively... 

The nitroazoles are widely used in the reaction of vicarious nucleophilic substitution of hydrogen. Vicarious nucleophilic C-amination is, practically, the single method of direct introduction of the amino group into nitro compounds. Using the vicarious nucleophilic substitution reaction we have successfully carried out the C-amination of some representatives of nitrobenzazoles, nitroazoles, and model compounds thereof and studied the structure of aminated products and the C-amination mechanism [673-678],... 

There has been some interest in the chemistry of aminonitroazoles when used as high energetic compounds. Data concerning direct introduction of the amino group into the nitroazole cycle have been absent in the literature till the present time. We have studied the vicarious nucleophilic substitution of l-methyl-4-nitropyrazole and also l-mcthyl-4-nitroimidazole (Table 3.10), 4-nitro-2-phenyl-1,2,3-triazole (Table 3.24), and nitrobenzimidazoles (Table 3.25) under the effect of 1,1,1-trim-ethylhydrazinium halides and 4-amino-1,2,4-triazole by NMR spectroscopy (DMSO-<76) (Scheme 3.5) [220, 272-278] ... 

The introduction of the amino group into position 7 considerably changes the chemical shifts of the atoms C-4, C-6, and C-7 as revealed by comparison with 4,6-dinitrobenzofurazan (-26.3 ppm upfield shift for C-6). The effect of the aryl substituent on the chemical shifts of dinitrobenzofurazan is negligible [749],... 

Gibson, M. S. Introduction of the amino group. Chem. Amino Group 1968, 37-77. 

Traube purine synthesis. Preparation of an appropriate 4,5-diaminopyrimidine by introduction of the amino group into the 5 position of 4-amino-6-hydroxy- or 4,6-diaminopyrimidines by nitrosation and ammonium sulfide reduction, followed by ring closure with formic acid or chlorocarbonic ester. 

Fused 2-hydroxyquinoline 29 exists in benzene, chloroform, dioxane, and ethanol in the hydroxy form (81ZOR803). On the addition of water or lower aliphatic carboxylic acids, the oxo form also appears reaching 75% in acetic acid. The introduction of bromine at the 3-position reduces the content of the lactam form in acetic acid to 45%, whereas the introduction of chlorine at position 6 reduces it to 60%. The introduction of the amino group at position 6, however, shifts the equilibrium in the opposite direction. 

Jegradaiiun (RuO —NaIO l of the furan gtouptoacaihoxy] group, migration of the benzoyl group from to C. and introduction of the amino group at C>. 

Theonelladins A-D A novel alkylpyridines (15-18) were isolated from Theonella swinhoei and exhibit mild activities in vitro against murine lymphomas and epidermoid carcinoma [29]. Two stereoselective total syntheses of theonelladins A-D have been published to date. A general strategy was used involving the construction of a common carbon skeleton 15a (see Scheme 4). Although the successful completion of the synthesis of 15-18 was achieved, the final introduction of the amino group into the molecule was not a clean step. 

Introduction of the amino group occurs at an early stage. This is supported by the incorporation of 26-aminodihydro-diosgenin (63) into solasodine (46) mDigitalis lanata (Gross et al., 1985). 

The static and dynamic adsorption capacity of the ACF increased on impregnation with PABA. The breakthrough time for formaldehyde and the amount adsorbed also increased on impregnation. The removal of formaldehyde involved both physisorption and chemisorption. The chemisorption was suggested to be due to the introduction of the amino groups in the impregnant. 

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