Mono-amino substitution products

B) MONO-AMINO SUBSTITUTION PRODUCTS ALKYL AMINES R-NHa AMINO ALKANES... 

Mono-substitution products of primary amines cannot easUy be prepared by direct action of the appropriate reagent for example, bromination of aniline yields largely the 2 4 6-tribomo derivative and nitration results in much oxidation. If, however, the amino group is protected as in acetanilide, smooth substitution occurs. Thus with bromine, />-bromoacetanilide is the main product the small quantity of the ortlio isomeride simultaneously formed can be easily eliminated by crystallisation. Hydrolysis of p-bromoacetanilide gives/ -bromoaniline ... 

The first synthesis1121 of A -foi-BocHN-alky]) amino acid building units used nucleophilic substitution of a-halocarboxylic acids or their esters 30 (Scheme 18) with mono-Boc-sub-stituted diamines 29. The nucleophilic substitution product 31 was reacted with Fmoc-OSu to give the orthogonally protected building unit 32. 

Berge reported that ethylhexyldimethyl-PABA is demethylated via a photo oxidation/decarbonylation sequence (23,24). The photoproducts produced are N-mono-methyl substituted or possess a free amino-group. These products have UV absorption spectra very similar to that of the starting dimethylamino compound. Therefore, this transformation cannot be detected, utilizing a simple spectral measurement (12,13). This is an example of a nonreversible photodegradation, which, in the spectral-only measurement, produces a result, which falsely indicates that the test substance/product has a higher photostability than is actually the case. 

The 1-substituted 3,5-dichlorothiatriazines 169 react further with alkyl alcohols, phenols, and mercaptans, usually nonselectively, leading to mono-and disubstituted products 176 and 177 (Scheme 28). The reaction with amines is more selective, since the introduction of the first amino substituent deactivates the last substitution, giving 178 as the major or sole product. If the amine is nucleophilic enough, the last substitution can proceed, affording 179. In the case of ammonia, disubstitution does not occur and derivatives 178 are formed almost quantitatively (Scheme 28) <2000JHC583>. 

Primary amines have been shown to act as directing groups for the C—H activation of anilines to give ortho azidation products. This novel reaction occurs regiose-lectively under mild conditions. Subsequent conversion of the amino group to Cl, I, Br, CN, OH, or H, illustrates the versatility of the azido products. Non-ortho-substituted electron-deficient and electron-rich anilines resulted in both mono- and di-substituted products, which could be separated by flash chromatography. Several functional groups when substituted at the ortho position of the aniline were well tolerated under these reaction conditions these include methyl, chloro, acetylene, and thiophenes. Examples are tabulated in Table 7.17. 

The Nenitzescu reaction generally occurs under relatively mild reaction conditions. Moreover mono-, di-, and tri-substituted quinones react with equal facility. Many enamines including p-aminoacrylonitriles, p-aminoacrylamides, and p-amino-a,p-unsaturated ketones react with quinones to form indole nuclei as well. The mild reaction conditions and the availability of the starting material render it attractive even in those instances where the yield of the product is low. ... 

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