Reduction reactions amine preparation

In addition to the nitrile and alcohol routes for fatty amine preparation, processes have been described by Unocal and Pennwalt Corporation, using an olefin and secondary amine (14—16) by Texaco Inc., hydrogenation of nitroparaffins (17—20) by Onyx Corporation, reaction of an alkyl haUde with secondary amines (21,22) by Henkel Cie, GmbH, reduction of an ester in the presence of a secondary amine (23) by catalytic hydroammonolysis of carboxyhc acids (24) and by the Hofmann rearrangement (25). 

The in-out bicyclic amines prepared by Simmons and Park bear a remarkable semblance to the cryptands but lack the binding sites in the bridges. As a result, these molecules interact with electrophiles in a fashion similar to other tertiary amines and generally do not exhibit strong interactions with alkali or alkaline earth metal ions. The in-out bicyclic amines are prepared by reaction of the appropriate acid chlorides and amines in two stages to yield the macrobicyclic amine after reduction of the amidic linkages. A typical amine is shown above as compound 18. 

The Zincke reaction has also been adapted for the solid phase. Dupas et al. prepared NADH-model precursors 58, immobilized on silica, by reaction of bound amino functions 57 with Zincke salt 8 (Scheme 8.4.19) for subsequent reduction to the 1,4-dihydropyridines with sodium dithionite. Earlier, Ise and co-workers utilized the Zincke reaction to prepare catalytic polyelectrolytes, starting from poly(4-vinylpyridine). Formation of Zincke salts at pyridine positions within the polymer was achieved by reaction with 2,4-dinitrochlorobenzene, and these sites were then functionalized with various amines. The resulting polymers showed catalytic activity in ester hydrolysis. ... 

Nonetheless, it was a fairly short step from octopus compounds to dendrimers, and the step was taken by Vogtle in the late 1970s when he attempted to use a cascade reaction to prepare a molecule of the dendrimer type that would now be considered a dendron rather than a fully developed dendrimer. It began with the addition of acrylonitrile to an anfine, followed by reduction of the nitrile to amine. This was followed by a further reaction with acrylonitrile, and the process was repeated several times to yield highly branched macromolecules. There were initially problems with the reduction step but these were overcome, and the preparation of these poly(propylene imine) dendrimers was later commercialized. 

The key intermediate in another total synthesis of secoquettamine (234), elaborated by Stevenson et al. (185), was 2-arylbenzofuran 241 prepared by a coupling reaction of the copper salt of 4-benzyloxyphenylacetylene with bromoisovanillin (Scheme 37). In the next step condensation with nitro-methane and reduction gave amine 242, which when N-methylated and debenzylated resulted in secoquettamine (234). 

In recent years, the importance of aliphatic nitro compounds has greatly increased, due to the discovery of new selective transformations. These topics are discussed in the following chapters Stereoselective Henry reaction (chapter 3.3), Asymmetric Micheal additions (chapter 4.4), use of nitroalkenes as heterodienes in tandem [4+2]/[3+2] cycloadditions (chapter 8) and radical denitration (chapter 7.2). These reactions discovered in recent years constitute important tools in organic synthesis. They are discussed in more detail than the conventional reactions such as the Nef reaction, reduction to amines, synthesis of nitro sugars, alkylation and acylation (chapter 5). Concerning aromatic nitro chemistry, the preparation of substituted aromatic compounds via the SNAr reaction and nucleophilic aromatic substitution of hydrogen (VNS) are discussed (chapter 9). Preparation of heterocycles such as indoles, are covered (chapter 10). 

In the chemistry described in Scheme 6.151, Coats and a group of researchers from Johnson and Johnson utilized successive reductive aminations and Suzuki cross-coupling reactions to prepare a 192-member library of tropanylidene benz-amides [295], This series of tropanylidene opioid agonists proved to be extremely tolerant with regard to structural variation while maintaining excellent opioid activity. 

Asymmetric catalytic reduction reactions represent one of the most efficient and convenient methods to prepare a wide range of enantiomerically pure compounds (i.e. a-amino acids can be prepared from a-enamides, alcohols from ketones and amines from oximes or imines). The chirality transfer can be accomplished by different types of chiral catalysts metallic catalysts are very efficient for the hydrogenation of olefins, some ketones and oximes, while nonmetallic catalysts provide a complementary method for ketone and oxime hydrogenation. 

Unsymmetrical secondary aliphatic amines have been prepared by reaction of alkyl halides with benzylidene amines and subsequent hydrolysis 814 by reaction of alkyl halides with alkyl amines 5 by reduction of amine-aldehyde adducts 8-8 and by dealkylation of tertiary amines with dibenzoyl peroxide. ... 

Amines can be prepared a number of ways. These methods include nucleophilic substitution reactions, reduction reactions, and oxidation reactions. 

A number of organic species, including amides, oximes, and nitriles, undergo reductive amination, a variety of reduction reactions that produce cimines. In general, these processes involve imines, R=N-R, or related species. Reduction processes include hydrogenation using Raney nickel as the catalyst (for nitriles), the reaction with sodium/EtOH (for oximes), and the use of lithium aluminum hydride, LiAlH (for amides or nitriles). Figure 13-16 illustrates the preparation of amphetamine by reductive amination. 

In order to place later chapters in proper context, the first chapter offers a comprehensive overview of industrially important catalysts for oxidation and reduction reactions. Chapters 2 and 3 describe the preparation of chiral materials by way of the asymmetric reduction of alkenes and ketones respectively. These two areas have enjoyed a significant amount of attention in recent years. Optically active amines can be prepared by imine reduction using chiral catalysts, as featured in Chapter 4, which also discloses a novel reductive amination protocol. 

A review which covered the different known methods for the preparation of chiral amines and analysis of the different chiral catalysts used, correlating them according to their efficiency, selectivity, and flexibility, has been presented.279 Reduction reactions of alkenes, arenes, alkynes and allenes resulting in the formation of two or more C-H bonds280 and reduction and addition reactions of alkynes to alkenes to form one or more C=C bonds281 have been reviewed. 

A Diels-Alder approach to varenicline was recently published by Dr. Reddy s Laboratories. Entry to a key bicyclic intermediate is achieved by an iodide-catalyzed Diels-Alder reaction of tetrabromo dimethyl pyrazine (47) with excess norbomadiene. Dihydroxylation of 48, oxidative cleavage, and reductive amination prepares N-p-methoxybenzyl varenicline (50), which is deprotected under transfer hydrogenation conditions to give varenicline (1) in 10% yield for the sequence.47 This approach continues the theme of building the piperidine of 1 through olefin oxidative cleavage and reductive amination, but by doing so late in the sequence however, the approach... 

In our selected example, Lehn and coworkers [80] reported the synthesis of a dynamic 12-member, template-directed imine library 1, obtained from the reversible condensation of three aldehydes (monomer set M, Figure 7.11), with four primary amines (monomer set M2, Figure 7.11) in buffered aqueous conditions, followed by irreversible reduction to amines 2 with sodium cyanoborohydride. The library was prepared in the presence of a large excess of M2, to prevent further condensation of an aldehyde onto the secondary amine product. A template-driven imine library 1 was prepared in the presence of the metalloenzyme carbonic anhydrase II (CAII). After the template-assisted, reversible dynamic reaction was complete, the reducing agent was added and the amine library 2 was produced (Figure 7.11). Without any... 

Phenylethylamine has been made by a number of reactions, many of which are unsuitable for preparative purposes. Only the most important methods, from a preparative point of view, are given here. The present method is adapted from that of Adkins,1 which in turn was based upon those of Mignonac,2 von Braun and coworkers,3 and Mailhe.4 Benzyl cyanide has been converted to the amine by catalytic reduction with palladium on charcoal,5 with palladium on barium sulfate,6 and with Adams catalyst 7 by chemical reduction with sodium and alcohol,8 and with zinc dust and mineral acids.9 Hydrocinnamic acid has been converted to the azide and thence by the Curtius rearrangement to /3-phenyl-ethylamine 10 also the Hofmann degradation of hydrocinnamide has been used successfully.11 /3-Nitrostyrene,12 phenylthioaceta-mide,13 and the benzoyl derivative of mandelonitrile 14 all yield /3-phenylethylamine upon reduction. The amine has also been prepared by cleavage of N- (/3-phenylethyl) -phthalimide 15 with hydrazine by the Delepine synthesis from /3-phenylethyl iodide and hexamethylenetetramine 16 by the hydrolysis of the corre-... 

Alkyl groups may be introduced into ammonia, a primary amine, or a secondary amine by means of an aldehyde or ketone in the presence of a reducing agent, such as molecular hydrogen and a catalyst, active metals and acids, or formic acid or one of its derivatives. When the reducing agent is formic acid or a derivative, the reaction is known as the Leuckart reaction and is discussed elsewhere (method 432). An excellent review of the preparation of amines by reductive alkylation has been presented. This article includes a discussion of the scope and utility of the reaction, a selection of experimental conditions, illustrative preparations, and a tabulation of primary, secondary, and tertiary amines prepared thereby. ... 

Several types of Schmidt reaction merit special mention (a) An interesting consequence of the factors governing migratory aptitudes is that acetanilides are the major (typically >95%) products of rearrangement of acetophenones. This leads to a practical alternative to nitration and reduction as a preparative route to aromatic amines , cf. reaction (24). (b) Product analyses showed that... 

Reduction of a-nitro-j6-hydroxybutyric acid to D,L-threonine [65] and similar reactions [33,66] have been investigated for the preparation of amino acids. The reduction to amine passes predominantly through the hydroxylamino derivative and only to a smaller degree through the oxime. 

REACTION (a) PREPARATION OF AN AZO DTE FROM A DIAZO-COMPOUND AND AN AMINE. (i) REDUCTION OF THE AZO-COMPOUND... 

The various possibilities for the preparation of chiral allylic amines or a aryl substituted amines are outlined in Figure 1.9. Although the addition reaction of a carbon nucleophile to an imine derived from an aryl substituted aldehyde is very efficient (B), the related addition to an a,p unsaturated imine (A) can sometimes proceed via a 1,4 addition pathway. Similarly, the asymmetric C=N reduction reaction (C and D) is sometimes hampered by the possibility of either obtaining conjugate reduction (in the case of C) or low enantioselectivities (in D when R = aryl). The addition of sp hybridized carbanions to imines (E) is a particularly effective... 

Stereoisomer ratios were determined by capillary gas chromatographic analysis of the jY-trifluo-roacetylated amines prepared, where necessary, by alane/THF reduction of the IMDA reaction products. 

A number of applications of the above-presented approach have been made in the synthesis of bicyclic amines. It has been used in the preparation of pyrrolo[l,2-a]indoles starting from N-trimethylsilylmethyl indoles, which are reacted with silver fluoride in an oxidation-reduction reaction to provide the desired products in good to excellent yields126 (equation 128). This same approach was applied to the preparation of some... 

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