Alkylation of amine

Unusual reducing properties can be obtained with borohydride derivatives formed in situ. A variety of reductions have been reported, including hydrogenolysis of carbonyls and alkylation of amines with sodium borohydride in carboxyHc acids such as acetic and trifluoroacetic (38), in which the acyloxyborohydride is the reducing agent. 

The imine, prepared from an amine and (C5H4N)(Me3C JH2)CO (TiC, toluene, reflux, 12 h NaOH, 80% yield), can be cleaved with coned. HCl (reflux). The protective group was used to direct a-alkylation of amines. 

A similar mechanism has been proposed for the alkylation of amines by p-nitrocumyl chloride. 

In addition to its uses in photography and medicine, iodine and its compounds have been much exploited in volumetric analysis (iodometry and iodimetry, p. 864). Organoiodine compounds have also played a notable part in the development of synthetic organic chemistry, being the first compounds used in A. W. von Hofmann s alkylation of amines (1850), A. W. Williamson s synthesis of ethers (1851), A. Wurtz s coupling reactions (1855) and V. Grignard s reagents (1900). 

Coe et al. reported an efficient modification for the preparation of /-substituted indole analogs for biology screening in good yield. The intermediate P-nitrostyrene 44, prepared from the condensation of 43 with DMFDMA, underwent methanolysis and reduction to provide the aniline acetal intermediate 45. Alkylation of amine 45 was carried out employing standard conditions of reductive alkylation to provide A-alkyl analogs represented by 46. The indole 47 was generated by formation of the oxonium ion (from 46) under acidic conditions, followed by cyclization, accompanied by loss of methanol. 

A. Attack by NH2, NHR, or NR2 at an Alkyl Carbon 10-44 Alkylation Of Amines Amino-de-halogenation (alkyl)... 

In addition, there are a few examples of heterogeneous nonaqueous sonochemistry, in both liquid-liquid and liquid-solid systems. Two recent reports have utilized ultrasonic agitation in place of or along with phase transfer catalysis for the preparation of dichlorocarbene from aqueous NaOH/CHCl3 (166), and for N-alkylation of amines with alkyl halides (167). Along the same lines, several papers have appeared in which... 

Ruthenium-catalyzed a-alkylations of amines have been reported (Equation (26)). 

The reductive alkylation of amines is called the Leuckart-Wallach reaction [112-115]. The primary or secondary amine reacts with the ketone or aldehyde. The formed imine is then reduced with formic acid as hydrogen donor (Scheme 20.27). When amines are reductively methylated with formaldehyde and formic acid, the process is termed the Eschweiler-Clarke procedure [116, 117]. 

HZ Sommer, HI Lipp, LL Jackson. Alkylation of amines. A general exhaustive alkylation method for the synthesis of quaternary ammonium compounds, (effects of hindrance) J Org Chem 36, 824, 1971. 

The catalytic effect of quaternary ammonium salts in the basic liquid liquid two-phase alkylation of amines [1-3] is somewhat unexpected in view of the low acidity of most amines (pKfl>30). Aqueous sodium hydroxide is not a sufficiently strong base to deprotonate non-activated amines in aqueous solution and the hydroxide ion is not readily transferred into the organic phase to facilitate the homogeneous alkylation (see Chapter 1). Additionally, it is known that ion-pairs of quaternary ammonium cations with deprotonated amines are decomposed extremely rapidly by traces of water [4]. However, under solidrliquid two-phase conditions, the addition of a quaternary ammonium salt has been found to increase the rate of alkylation of non-activated amines by a factor of ca. 3-4 [5]. Similarly, the alkylation of aromatic amines is accelerated by the addition of the quaternary ammonium salt the reaction is accelerated even in the absence of an inorganic base, although under such conditions the amine is deactivated by the formation of the hydrohalide salt, and the rate of the reaction gradually decreases. Hence, the addition of even a weak base, such as... 

The most widely used iridium catalyst for the V-alkylation of amines with alcohols is [Cp lrCl2]2, which was identified and developed by Fujita, Yamaguchi, and CO workers [94]. Aniline 111 has been selectively alkylated by a range of... 

Scheme 26 Alkylation of amines with alcohols by borrowing hydrogen...

Complexation of [Cp IrCl2]2 with iV-heterocyclic carbenes has led to complexes such as 25, developed by Peris and coworkers [107, 108], and 133, developed by Crabtree and coworkers [12]. Complex 24 is activated by the addition of silver triflate and is effective for the iV-alkylation of amines with alcohols and for the iV-alkylation of anilines with primary amines. Complex 25 has also been shown to couple benzyl alcohol 15 with a range of alcohols, including ethanol 134, to give ether products such as ether 135 (Scheme 31). Complex 133 was an active hydrogen transfer catalyst for the reduction of ketones and imines, using 2-propanol as the hydrogen source. It was also an effective catalyst for the iV-alkylation of amines... 

The development of versatile and efficient methods for the synthesis of amines has long been an active area of research, mainly because a wide variety of amines play important roles in many fields of organic chemistry. The N-alkylation of amines with alcohols represents an attractive method for synthesizing various amines because it does not generate any wasteful byproducts (H2O is the only stoichiometric coproduct). Although several catalytic systems for this process have been studied using transition-metal catalysts [53-57], most of these require a high reaction temperature (>150°C). 

The [Cp IrCl2]/K2C03 system serves as an efficient catalyst for the N-alkylation of amines 106 with alcohols 107 (Equation 10.25) [48]. Alternatively, [IrCl(cod)]2... 

---