Aldehydes to amines

The submitters state that Avith a 1 1 mole ratio of aldehyde to amine the yield dropped to 75%, presmnably because more of the aldehyde was reduced. 

The reaction occurs rapidly at alkaline pH (7—10), with higher pH values resulting in better yields due to faster Schiff base formation. To ensure complete conversion of available aldehydes to amines, add the ammonia or diamine compound to the reaction in at least a 10-fold molar excess over the expected number of formyl groups present, Diamines that are commonly used for this process include ethylene diamine, diamino-dipropylamine (3,3 -iminobispropylamine), 1,6-diaminohexane, and the Jeffamine derivative EDR-148 containing a hydrophilic, 10-atom chain (Texaco Chemical Co.). 

Reductive amination. Conversion of ketones or aldehydes to amines is usually accomplished by reduction of the carbonyl compound with sodium cyanoborohydride in the presence of an amine (Borch reduction, 4, 448-449). However, yields are generally poor in reactions of hindered or acid-sensitive ketones, aromatic amines, or trifluoromethyl ketones. Yields can be improved markedly by treatment of the ketone and amine first with TiCl4 or Ti(0-i -Pr)42 in CH2C12 or benzene to form the imine or enamine and then with NaCNBH3 in CH3OH to effect reduction. Note that primary amines can be obtained by use of hexamethyldisilazane as a substitute for ammonia (last example). 

A popular and effective method for converting aldehydes to amines is through a reductive amination protocol. Typically, the aldehyde and amine react to fonn an intermediate imine or iminiiim ion and tlien a reducing agent (i.e., sodium triacetoxyborohydride) is added to carry out the reduction of the intermediate species to afford the amine. The reaction is accelerated in the presence of acetic acid (0.1 -3 equivalents). Reviews (a) Baxter, E. W. Reitz, A. B. Org. React. 2002, 59, 1-714. (b) Hutchins, R. O. In Comprehensive Organic Synthesis Trost, B. M. Fleming, L, Eds. Pergamon Press Oxford, U. K., 1991 Vol. 8, Chapter 1.2 Reduction of C=N to CHNH by Metal Hydrides, pp. 25-54. 

The synthesis of ring-fused aminals under solvent-free conditions has recently been reported (Scheme 2.3). Simply heating the neat reagents at 130 °C for 45-60 min generated the desired products in moderate-to-high yields. Although a 1 4 ratio of aldehyde to amine was needed for a successful reaction, this one-pot process represents an efficient way to prepare ring-fused aminals. 

Hantzsch ester (2, R = Et) and an organocatalyst -benzyl isothiouronium chloride, prepared from thiourea, catalysed the reductive amination of aromatic, aliphatic, heterocyclic, and cyclic aldehydes to amines in high yields. Aliphatic aldehydes reacted with difficulty and required a higher temperature. Nitro, nitrile, and carbonyl moieties were not reduced. ... 

PEG/dextran aldehyde was developed as biocompatible tissue adhesive [77]. It consisted of a relatively short-chain PEG polymer (linear PEG of 2 kDa or 8-arm PEG of 10 kDa) containing amine-terminated groups, and dextran containing aldehyde groups. Aldehyde to amine ratios of 1, 3, and 10 were examined for... 

It will also reduce acid chlorides, acid anhydrides and aldehydes to primary alcohols, ketones to secondary alcohols, and amides to the corresponding amines R-CONHi -> R CHiNH. Nitro-hydrocarbons if aromatic are... 

Commercially, pure ozonides generally are not isolated or handled because of the explosive nature of lower molecular weight species. Ozonides can be hydrolyzed or reduced (eg, by Zn/CH COOH) to aldehydes and/or ketones. Hydrolysis of the cycHc bisperoxide (8) gives similar products. Catalytic (Pt/excess H2) or hydride (eg, LiAlH reduction of (7) provides alcohols. Oxidation (O2, H2O2, peracids) leads to ketones and/or carboxyUc acids. Ozonides also can be catalyticaHy converted to amines by NH and H2. Reaction with an alcohol and anhydrous HCl gives carboxyUc esters. 

Primary aromatic amines react with aldehydes to form Schiff bases. Schiff bases formed from the reaction of lower aUphatic aldehydes, such as formaldehyde and acetaldehyde, with primary aromatic amines are often unstable and polymerize readily. Aniline reacts with formaldehyde in aqueous acid solutions to yield mixtures of a crystalline trimer of the Schiff base, methylenedianilines, and polymers. Reaction of aniline hydrochloride and formaldehyde also yields polymeric products and under certain conditions, the predominant product is 4,4 -methylenedianiline [101 -77-9] (26), an important intermediate for 4,4 -methylenebis(phenyhsocyanate) [101-68-8], or MDI (see Amines, aromatic amines, l thylenedianiline). 

Biomters are most economic when apphed to low-concentration gas streams (<1000 ppm) that are also oxygen rich. Greater than 90 percent destruction efficiencies can be obtained for water-soluble organics such as alcohols, aldehydes, and amines. Water-soluble inor-... 

Reductive amination ol aldehydes or ketones by cyanoborohydride (or tnacetoxyborohydride) anion Selective reduction of carbonyls to alcohol, oximes to N alkylhydroxylarmnes, enamines to amines... 

Lithium aluminum hydride (LiAlH4) is the most powerful of the hydride reagents. It reduces acid chlorides, esters, lactones, acids, anhydrides, aldehydes, ketones and epoxides to alcohols amides, nitriles, imines and oximes to amines primary and secondary alkyl halides and toluenesulfonates to... 

Additional evidence that a dynamic equilibrium exists between an enamine, N-hemiacetal, and aminal has been presented by Marchese (41). It should be noted that no acid catalysts were used in the reactions of aldehydes and amines discussed thus far. The piperidino enamine of 2-ethylhexanal (0.125 mole), morpholine (0.375 mole), and p-toluene-sulfonic acid (1.25 x 10 mole) diluted with benzene to 500 ml were refluxed for 5 hr. At the end of this time the enamine mixture was analyzed by vapor-phase chromatography, which revealed that exchange of the amino residue had occurred in a ratio of eight morpholine to one piperidine. Marchese proposed a scheme [Eqs. (4), (5) and (6)] to account for these... 

Mino and Kaizerman [12] established that certain. ceric salts such as the nitrate and sulphate form very effective redox systems in the presence of organic reducing agents such as alcohols, thiols, glycols, aldehyde, and amines. Duke and coworkers [14,15] suggested the formation of an intermediate complex between the substrate and ceric ion, which subsequently is disproportionate to a free radical species. Evidence of complex formation between Ce(IV) and cellulose has been studied by several investigators [16-19]. Using alcohol the reaction can be written as follows ... 

An example of how information from fragmentation patterns can be used to solve structural problems is given in Worked Example 12.1. This example is a simple one, but the principles used are broadly applicable for organic structure determination by mass spectrometry. We ll see in the next section and in later chapters that specific functional groups, such as alcohols, ketones, aldehydes, and amines, show specific kinds of mass spectral fragmentations that can be interpreted to provide structural information. 

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