Azide, amines from reduction

Atorvastatin, structure of, 105. 516 ATP (see Adenosine triphosphate) ATZ, see Anilinothiazolinone, 1031-1032 Aufbau principle. 6 Axial bonds (cyclohexane), 119 drawing, 120 Azide, amines from, 929 reduction of, 929 Azide synthesis, 929 Azo compound, 944 synthesis of, 944-945 uses of. 945... 

Benzodiazepin-2-ones are converted efficiently into the 3-amino derivatives by reaction with triisopropylbenzenesulfonyl (trisyl) azide followed by reduction <96TL6685>. Imines from these amines undergo thermal or lithium catalysed cycloaddition to dipolarophiles to yield 3-spiro-pyrrolidine derivatives <96T13455>. Thus, treatment of the imine 50 (R = naphthyl) with LiBr/DBU in the presence of methyl acrylate affords 51 in high yield. 

One problem with this method is that the workup must be done carefully as die amine products tend to complex tenaciously with the aluminum salts formed from the LAH upon workup and thus are not recovered easily. There are standard workups which avoid these issues, but these should be followed carefully. Reduction of azides by catalytic reduction, phosphine or phosphite reagents, or Sn(II) chloride are all effective methods. The azides are also available from displacement reactions and give primary amines upon reduction. 

The synthesis of secondary amines from azides is efficient in terms of chemos-electivity [57] and has found valuable applications in the preparation of diamines [58,59], m-alkylaminoboronic esters [60], and in Diels-Alder-based amination reactions [61]. A convenient general route to open-chain polyamines, which play major roles in cellular differentiation and proliferation, has also been developed using the reductive alkylation of aliphatic aminoazides by (co-halogenoalk-yi)dichloroboranes as a key step [62] (Scheme 21). 

Exposure of sulfolane 261 to sodium azide and mesylation regioselectively afforded mesylate 262, which was transformed into aziridine 263 by a three-step sequence involving azide to amine Staudinger reduction, acetylation, and ring closure. The trans 1,2-diamino derivative 264 was quickly obtained from 263 by azide opening of the aziridine ring, followed by reduction. 

There are many instances in which the introduction of amines with specific substitution patterns is desired. With the abundance of structurally diverse commercially available amines from which to choose, the use of these compounds as nucleophiles is extremely valuable. While the example illustrated in Scheme 6.29 focuses on the hydrazine displacement of a secondary tosylate from a furanose sugar derivative [56], this type of reaction is easily achieved with most primary and secondary amines. Where the introduction of direct NH2 groups is desired, the best methods rely on the reduction of azides or nitro groups, or the hydrolysis (hydrazinolysis) of imides [32]. 

Amines from azides. The oxide reagent is converted in situ into BujSnH by a hydrosilane such as PhSiHj to effect the reduction. 

Amines from azides. Reduction of various azides to amines... 

Amines from azides. The rapid reduction occurs at room temperature using MejSil generated in situ from Me SiCl and Nal in MeCN. 

Reduction of aldehydes and ketones allylic alcohols from a, 3-unsaturated aldehydes and ketones alcohols from carboxylic acid chlorides amines from aliphatic azides.21 ... 

A later-developed method to obtain amines from azides consists in their reduction with propane-1,3-dithiol,employing ethyldiisopropylamine as a base. The transformations reported proceeded rapidly and resulted in, 2-trans selectivity. Unverzagt described the reduction of the azido heptasaccharide 221 by this dithiol method, to give exclusively the p amine 222. In contrast, reduction of 221 by Raney nickel resulted in both anomers 222 and 223, with p a = 7 3. A corresponding reduction of the azido octasaccharide gave a 52% yield however, a low yield of 35% was observed in the reduction of the thio sugar azide 68 with propane-1,3-dithiol... 

Alkylation of Azide Ion and Reduction A much better method for preparing a primary amine from an alkyl halide is first to convert the alkyl halide to an alkyl azide (R — N3) by a nucleophilic substitution reaction, then reduce the azide to a primary amine with lithium aluminum hydride. 

As shown in Scheme 12.95, the methylcarbamate was removed with hydrogen bromide (HBr) in acetic acid to form hydrobromide salt. When the amino hydrobromide salt was heated in acetic acid, a bromolactam was generated from the presumed aziridine intermediate and then treatment of the bromolactam with lithium azide in dimethylformamide produced a cis azidolactam, which then yielded the corresponding amine on reduction. Hydrolysis of the lactam with aqueous barium hydroxide ([Ba(OH)2] then produced the diamino acid, and addition of phosgene (COCI2) in aqueous sodium bicarbonate (NaHCOs) produced bisnorbio-tin, which was isolated as the corresponding methyl ester. 

The resulting 2-benzylthioethylamine could be debenzylated by treatment with sodium in liquid ammonia. However, when 2-benzylthioethylamine was treated with carbobenzyloxy-P-alanine azide (prepared from carbobenzyloxy-P-alanylhydrazide by nitrosation), 2-benzylthio-7V-(carbobenzyloxy-P-alanyl)ethyl-amine formed. Reduction with sodium in liquid ammonia was sufficient to remove both the benzyl and carbobenzyloxy protecting groups and, as noted above, reaction with pantolactone yielded pantetheine. Phosphorylation to the mono- and diphosphates of pantetheine has been effected with the corresponding dibenzylphospho-nates (vide supra, ATP). 

Hydroxy-lactone 6.75 was prepared in several steps from glutamic acid (see chapter 2, section 2.2) and then opened by treatment with iodotrimethylsilane to give 6.76.Displacement of iodide with sodium azide, followed by reduction to the amine and hydrolysis, gave R-GABOB in 56% overall yield (>99%ee). 

Di-t-butyl chromate and its pyridine adduct are suitable for large-scale oxidations of alcohols to ketones, thus cyclododecanol was converted into cyclododecanone (97 Alcohols are easily separated from non-hydroxylic compounds via their calcium chloride complexes. This method was used to separate cyclododecanone and cyclododecanol and is suitable for the separation of large quantities of material." All-cis-cyclododecane-l,5,9-triol was converted into the all-cis-tri-amine by tosylation, azide substitution, and reduction, and the amine acylated with 2,3-dimethoxybenzoyl chloride to give the tri-amide, an analogue of enterochelin. ... 

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