Amines reaction with lithium

A similar sequence starting with the acylation product (76) from metachlorophenylacetonitrile gives the halogenated tricyclic ketone 83. Condensation of that intermediate with ethyl bromoacetate in the presence of zinc (Reformatsky reaction) gives the hydroxyester 84. This product is then in turn dehydrated under acid conditions (85), saponified to the corresponding acid (86), and converted to the dimethyl-amide (87) by way of the acid chloride. The amide function is then reduced to the amine (88) with lithium aluminum hydride catalytic hydrogenation of the exocyclic double bond completes the synthesis of closiramine (89). This compound also exhibits antihistaminic activity. 

The sensitivity of position 2 in 4-chloroquinazoline for nucleophilic addition was also demonstrated in the reaction with lithium piperidide (73RTC460). Whereas in the amination with potassium amide/liquid ammonia no open-chain intermediate could be isolated, with lithium piperi-dide/piperidine the open-chain compound ort/z6>-(piperidinomethy-leneamino)benzonitrile (78,60%) was obtained, in addition to 4-piperidino-quinazoline (80,19%) (Scheme 11.35). The formation of 80 from 78 involves... 

A detailed study of the conversion of 3,4-dichloro-l,2,5-thiadiazole into 3,4-diamino-l,2,5-thia-diazole has been carried out <76JHC13>. Reaction with lithium or sodium amide produces only 4% of the diamine together with cyano-containing by-products, a consequence of direct attack on sulfur. Use of a less powerful nucleophile, ammonia or potassium phthalimide, resulted in an increased attack on carbon and produced the diamine in 24% and 66% yields, respectively. Secondary amines, e.g. morpholine <76JOC3l2l> and dimethylamine <72JMC315>, produce the normal displacement products. The reaction of dichlorothiadiazole with potassium fluoride in sulfolane gives a mixture of 3-chloro-4-fluoro and 3,4-difluoro-l,2,5-thiadiazole <82CB2135>. 

Azomethine ylides such as 64 can be generated from tertiary amine A-oxides (63) by reaction with lithium diisopropylamide (EDA) (Scheme 12.22) (97). Several different chiral A -substituted azomethine ylides were prepared in this manner. The best results were obtained when using 64 in 1,3-dipolar cycloaddition with alkenes, but the de values obtained of the product 65 were <60%. 

Nitriles (RCN) can be reduced to primary amines (RCH2HN2) with lithium aluminium hydride that provides the equivalent of a nucleophilic hydride ion. The reaction can be explained by the nucleophilic attack of two hydride ions ... 

Kirmse and coworkers have studied the reaction of alkanediazonium ions with amines and with lithium azide Cyclopropanediazonium ions give azo coupling products 6 and 7 with dimethylamine and with ethylamine, respectively (1) K However, no azo coupling of 1 with phenols was observed. In the reaction... 

This sequence is well illustrated by the synthesis of 3a-aminocholes-tane (72) from cholestanyl-3j3-/>-toluenesulphonate . Reaction of the equatorial /(-toluenesulphonate with sodium azide in aqueous di-methylformamide or dimethylacetamide afforded the axial azide (73) which was reduced to the amine (72) with lithium aluminium hydride... 

Lactams. This N-(cyanomethyl)amine reacts with lithium ester enolates to afford 4-unsubstituted p-lactams in 60-75% yield (equation I). This reaction is generally applicable to N-(cyanomethyl)amines. 3-Amino-p-lactams can be ob-... 

A series of ferrocene-based mono and bifunctional tris(pyrazolyl)-borates bearing either methyl or phenyl substituents at the 3-position has been prepared via a fnms-amination reaction. The lithium salts have been converted in the analogous T1 species and [Tl(Fc(Tpph))] has been also structurally characterized. These compounds feature monomeric units with tridentate Fc(Tpph) in striking contrast to the sterically less congested [Tl(Fc(Tp))] that forms polymeric rods in the solid state. In the same paper the authors reported the structure of Tl(Tp) for purpose of comparison.192... 

The reaction of ( )-3,3-dimethyl-l-butene-l,2-r/2 with hydrogen cyanide and of ( )-3,3-dimethyl-l-butene-l-d2 with deuterium cyanide stereospecifically proceeds in a cis fashion with Pd(Diop)2 used as the catalyst precursor20,24. The stereochemistry of the products is verified by NMR and characterization of the thiourea derivatives of the corresponding amine obtained with lithium aluminum deuteride. No //wu-addition products exceeding a limit of 5-10% can be detected. 

The Birch reductions of C C double bonds with alkali metals in liquid ammonia or amines obey other rules than do the catalytic hydrogenations (D. Caine, 1976). In these reactions regio- and stereoselectivities are mainly determined by the stabilities of the intermediate carbanions. If one reduces, for example, the a, -unsaturated decalone below with lithium, a dianion is formed, whereof three different conformations (A), (B), and (C) are conceivable. Conformation (A) is the most stable, because repulsion disfavors the cis-decalin system (B) and in (C) the conjugation of the dianion is interrupted. Thus, protonation yields the trans-decalone system (G. Stork, 1964B). 

In each of the following reactions an amine or a lithium amide derivative reacts with an aryl halide Give the structure of the expected product and specify the mechanism by which it is formed... 

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