Hydrogenation, catalytic benzyl amines

Reductive alkylation of ammonia has been proved an effective and highly versatile method for obtaining primary amines. The most satisfactory conditions have been catalytic hydrogenation (Raney nickel) of the carbonyl compound in an ethanolic solution of ammonia under pressure ranging from 20 to 150 atm. and at temperatures in the range of 40° to 150°. Typical amines prepared in this manner include benzyl-amine and 2-aminoheptane (80%). With liquid ammonia and no... 

The catalytic hydrogenation of the benzoylformic acid amides of optically active amino acid esters was carried out. When the (5)-amino acid ester was used, the resulting mandelic acid had the (R)-con-figuration. When pyruvic acid amides of optically active benzylic amines were hydrogenated over palladium, optically active lactic acid was obtained in relatively high enantiomeric excess (ee 60%). The... 

Benzylic amines are particularly susceptible to hydrogenolysis by catalytic hydrogenation or dissolving metal reduction. " Note that the Wolff-Kishner reduction in 19-61 involved formation of a hydrazone and deprotonation by base led to loss of nitrogen and reduction. Ceric ammonium nitrate in aqueous acetonitrile has also been shown to reductively cleave the V-benzyl group. Primary amines have been reduced to RH with hydroxylamine-O-sulfonic acid and... 

Products related in structure to 249 and 250 could be accessed through condensation of benzyl amine with tetronic acid (256) followed by aza-annulation with acrylic anhydride to give 258 (eq. 52).58 Stereoselective generation of the cis ring fusion of 259 was accomplished by catalytic hydrogenation. 

Modification of the products that resulted from the aza-annulation of tetrasubstituted enamine substrates with acrylate derivatives was very limited. The aza-annulation of benzyl ester 496 with the mixed anhydride, a mixture (497) preformed from EtC CCl and sodium acrylate, provided a route to 498 in >98 2 diastereoselectivity (eq. 100), which allowed access to the carboxylic acid derivative 499 through catalytic hydrogenation.1 Further elaboration of either the ester or the acid derivative was unsuccessful, possibly due to the steric congestion around the reactive functionality. Extended hydrogenation did not reduce the enamine functionality, as observed in related substrates, and 498 was relatively stable to acidic hydrolysis conditions. In addition, DCC (N,N -dicyclohexylcarbodiimide) coupling of acid 499 with either benzyl amine or glycine ethyl ester was unsuccessful. 

What happens to them is a hydrogenolysis—a reaction that is liable to occur under catalytic hydrogenation conditions whenever a heteroatom (in particular O or N) finds itself bonded to a carbon atom adjacent to a benzene ring, in other words with benzylic amines, alcohols or ethers. 

A second-generation process ronte was developed that improves upon the initial process route (Scheme 6). - - In this simplified process approach, the molecular symmetry of the starting caronic anhydride was maintained to the latest stage possible. Caronic anhydride (30) was initially converted directly to imide 40 by heating with either ammonium hydroxide or formamide with DMAP under Dean-Stark conditions. In an alternative two-step protocol, heating of 30 with benzyl amine produced an intermediate benzyl imide, which was deprotected to 40 under catalytic hydrogenation conditions. Reduction of imide 40 with lithium aluminum hydride afforded 41, which was desymmetrized under oxidative conditions to produce racemic imine 42. Diastereoselective cyanation favored trans-43, which underwent methanolysis under Pinner conditions. Finally, classical resolution by crystallization with D-DTTA afforded 24 as the D-DTTA salt with >95% ee. 

Synthesis of 210 was started from preparation of chiral diamine 211 (Scheme 50) [172], In particular, D-serine methyl ester was converted to iV-benzyl derivative 212, which was transformed into carboxylic acid 212 using reaction with chloroacetyl chloride and subsequent hydrolysis. Carboxylic acid 212 was subjected to coupling with benzyl amine, reduction, reaction with ethyl oxalyl chloride and reductive cyclization to give bicyclic compound 213. Finally, 211 Two-step reduction of 213 led to the formation of diamine 211, which was isolated as dihydrochloride. Reaction of 211 with dichloro derivative 215 and then - hydrazine hydrate gave the product 216, which was coupled with carboxylic acid 217 and subjected to catalytic hydrogenation to give 210. 

Based upon the results of mechanism studies, a proposed mechanism containing two catalytic cycles was concluded by the authors. Firstly, benzylic radical is formed by the hydrogen abstraction of the terf-butoxy radical, which is well supported by literatures. The benzylic radical may be oxidized by iodine to give the benzylic cation with the generation of iodide ion. The interaction between iodide ion and TBHP would regenerate the terf-butoxy radical and finish the first catalytic cycle. Secondly, benzylic iodide is formed as a result of the reaction between benzylic cation and iodide ion, which is then converted into benzaldehyde by a DMSO participated Komblum oxidation. Finally, the iodide ion was oxidized back to iodine by TBHP to finish the second catalytic cycle (Scheme 4.17). Benzylic amine or alcohol may be formed from the benzylic cation. As confirmed in the control experiments, they can also lead to the nitrile product under standard condition. 

Schistosoma japonicum. The carbobenzoxy (CBz) protected template 160 was initially converted to the a, p-dehydrolactone 161 via the phosphate ester, before undergoing cycloaddition to ylide 162, generated in situ by acidic treatment of A(-benzyl-A(-(methoxymethyl)trimethylsilyl amine. The resultant cycloadduct (163) was isolated in 94% yield as a single diastereoisomer. Destructive template removal, by catalytic hydrogenation, released (5)-( )-cucurbitine, after ion-exchange chromatography, as the free amino acid in 90% yield (Scheme 3.46). 

The N-alkylation of amines with alcohols [63] can also be carried out with Ir catalysts through a similar domino sequence reaction. In this case, the aldehyde/ketone resulting from oxidation is condensed with an amine to the corresponding imine, which is hydrogenated to the alkylated amine [63]. By way of example, the reaction of benzyl alcohol with aniline in toluene afforded benzylaniline in a 88% isolated yield by using catalytic amounts of [ lr(/z-Cl)Cp Cl 2]/K2C03. 

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