Reductive amination of carbonyl

The practical applications of NaBH4 reductions on mineral surfaces for in situ generated SchifFs bases have been successfully demonstrated. The solid-state reductive amination of carbonyl compounds on various inorganic solid supports such as alumina, clay, silica etc. and especially on K 10 clay surface rapidly afford secondary and tertiary amines [126]. Clay behaves as a Lewis acid and also provides water from its interlayers thus enhancing the reducing ability of NaBH4 [22], 

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The Leuckart-Wallach reaction is the oldest method of reductive amination of carbonyl compounds. It makes use of formamide, formic acid or ammonium formate at high temperature. The final product is a formamide derivative, which can be converted to an amine by reduction or hydrolysis. The method has been applied to the preparation of 1,2-diamines with a norbornane framework, which are interesting rigid analogues of 1,2-diaminocyclohexanes. As a matter of fact, starting from N-acetyl-2-oxo-l-norbornylamine 222, the diamide 223 was obtained with excellent diastereoselectivity and then converted to the M-methyl-N -ethyl derivative 224 by reduction with borane [ 104] (Scheme 34). On the other hand, when the reac-... 

Tab. 3.8 Microwave-mediated Leuckart reductive amination of carbonyl compounds in 30 min.

Sodium cyanoborohydride [123], sodium triacetoxyborohydride [124] or NaBH4 coupled with sulfuric acid [125] are common agents used for the reductive amination of carbonyl compounds. These reagents either generate waste or involve the use of corrosive acids. The environmentally friendlier procedures developed by Varma and coworkers have been extended to a solvent-free reductive amination protocol for carbonyl compounds using moist montmorillonite K 10 day supported sodium borohydride that is facilitated by microwave irradiation (Scheme 6.39) [126]. 

Scheme 6.39 Reductive amination of carbonyls using clay-supported sodium borohydride.

Reductive amination, of carbonyl compounds, 16 573 Reductive bleaching, 21 440 Reductive dechlorination defined, 3 757t Reductive dehalogenation defined, 3 757t... 

Reductive amination of carbonyl compounds, 59, 1 71, 1 Reductive cyanation, 57, 3 Redutive desulfonylation, 72, 2 Reductive desulfurization of thiol esters,... 

Varma, R.S. and Dahiya, R., Sodium borohydride on wet clay solvent-free reductive amination of carbonyl compounds using microwaves, Tetrahedron, 1998, 54, 6293-6298. 

The C=N bonds of imines, oximes and hydrazones can be hydrogenated to form the corresponding amines even under ambient conditions on Pt, Pd, Rh and Raney Ni catalysts in acidic, neutral or basic media (equation 42). The imines, furthermore, are intermediates in the hydrogenation of nitro compounds, nitriles and oximes, and likewise play a key role as intermediates in the reductive amination of carbonyl compounds. 

Reductive amination of carbonyls.1 This borohydride is generally superior to sodium cyanoborohydride for reductive animations with weakly basic amines. 

A solvent-free reductive amination of carbonyl compounds using sodium borohydride supported on moist montmorillonite K10 clay also was facilitated by microwave irradiation (Scheme 8) [54]. Clay served the dual purpose of a Lewis acid and provided water from its interlayers to enhance the reducing ability of NaBH4. 

The reduction of 2-imino ketones is performed with Bu2SnClH-HMPA to give 2-amino ketones where no reduction of the carbonyl group takes place.84 The reductive amination of carbonyl compounds is one of the most convenient routes to various secondary amines. The high imine selectivity of Bu2SnClH-HMPA can be applied to... 

The two most general amine syntheses are the reductive amination of carbonyl compounds and the reduction of amides. Show how these techniques can be used to accomplish the following syntheses. 

Riermeier [1] prepared amines in high yields by reductive amination of carbonyl-containing compounds using hydrogen and primary or secondary amines with [Rh(COD)Cl]2 and 2,2 -bis[[bis(3-sulfophenyl)phosphino]-meth-yl]-4,4, 7, 7 -tetrasulfo-1,1 -binaphthyl octasodium as catalysts as illustrated below. When the reaction was duplicated using [Ir(COD)Cl]2 alone, only 6% 2-butylamine was incorporated. 

Reductive amination of carbonyl compounds. Sodium cyanoborohydride has been the reductant of choice for this reaction, even though it is highly toxic (4, 448-449). Borane-pyridine is recommended as a nontoxic substitute. The reactions are conducted in acetic acid, in which this borane is fairly stable, and a co-solvent such as CH2CI2 or THE... 

Reductive amination of carbonyl compounds. This reagent effects reductive ami-nation of aldehydes or ketones with amines (equation 1). Yields tend to be only moderate with anilines, but are high with aliphatic amines. 

Reductive amination of carbonyl compounds with ammonia or amines in the presence of a reducing agent has been discussed (method 431). When the reducing agent is formic acid or a derivative, the products are the formyl derivatives of primary or secondary amines or the formates of tertiary amines. These intermediates readily furnish the amines, A critical discussion of the reaction along with experimental conditions and procedures and a tabular survey of compounds has been presented. ... 

Stereospecific Reductive Amination of Carbonyl Compounds. Catalytic or chemical reduction of chiral imines derived from (1) often proceeds with high diastereoselectivity. Reductive removal of the a-methylbenzyl group yields chiral primary amines (eq 18 and 19). - ... 

Table 7 Reductive Amination of Carbonyls with NaBH3CN...

Another method for reductive amination of carbonyl compounds is based on the electroreduction of oximes in aqueous media. Thus, sugar oximes were reduced to their corresponding glycamines in good yields (Hg, KCl, acetate buffer). Similar reductions of oximes derived from furfural, salicylaldehyde, benzophenone and cyclohexanone have also been described, " but reports of preparative electrolyses in strictly aprotic media seem to be absent in the literature. 

Sodium triacetoxyborohydride Na[BH(OAc)3] ° and hydrogenation (H2, Pd/C) are used as alternatives to sodium cyanoborohydride for the reductive amination of carbonyl compounds. Also, Zn[BH4]2 is a particularly effective agent for the reductive amination of a,p-unsaturated aldehydes and ketones. ... 

Reduction ofimines. A mixture of Bu SnClj and Bu SnHj generates BujSnfCljH which saturates imines when complexed with HMPA. Thus, a-amino ketones are obtained from the corresponding imino ketones. Direct reductive amination of carbonyl compounds is also achieved (11 examples, 70-99%). ... 

Secondary amines. The reductive amination of carbonyl compounds with MeNHj HCl is easily accomplished. Triediylamine is present in the reaction mixture. 

Reductive amination of carbonyl compounds (including those belonging to heterocyclic series) with borohydride- and borane-reducing agents 02OR(59)l. 

Reductive amination of carbonyl compounds. Method A. N-octylbenzylamine (typical procedure). AAMF (30 mL) suspension of benzylamine (1.67 g, 15 mmol), octanal (1.55 g, 15 mmol), EtjN (7.0 mL, 50 mmol) and Al2Te3 (6.1 g, 14 mmol) is refluxed. The reaction is monitorized by GLC and H2O (3 mL, 168 mmol) is added at 15°C after 30 min. The het-erogeneons mixtnre is refluxed for another 30 min. The black solid is removed by filtration and the filtrate dried (CaCOj) and evaporated. The residne is distilled, giving the prodnct (2.7 g (80%) b.p. 108-112°C/1 torr). 

Ionic reduction enables efficient reductive amination of carbonyls. Although several reductive amination procedures have been developed, drawbacks had to be addressed - the requirement of excess amine to bias the equilibrium to the imine side and the unavoidable formation of overalkylation products. In sharp contrast, on treatment of a 1 1 mixture of carbonyl and amine hydroperchlorate wifh BusSnH in DMF, the desired amines were prepared in satisfactory yield wifhout contamination by overalkylation products (Scheme 12.122) [224]. 

Riermeier, T, Haack, K. J., Dingerdissen, U., Boerner, A., Tararov, V., and Kadyrov, R. (2005) Method for producing amines by homogeneously catalyzed reductive amination of carbonyl compounds, U.S. Patent No. 6884887, Degussa AG, Germany. 

LEUCKART - WALLACH ReductiveAmination Reductive amination of carbonyl groups with amines and formic add or H2-NI (Miquonac) or NaBHa (see Boreh). 

Primary amines are obtained by reductive amination of carbonyl compounds in two steps." The iminating agent is made up from (i-PrO)4Ti, NH4CI, and Et N, and the reducing agent is NaBH4. 

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