Amines, alkylation with alcohols

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... 

The alkylation with alcohols and amines can lead to alkyl derivatives or a-hydroxy and a-aminoalkyl derivatives according to the nature of the heteroaromatic base and the reaction conditions. The intermediate products in both cases are, however, the a-hydroxy and a-aminoalkyl dihydro derivatives, which can be aromatized by disproportionation or oxidation, while the loss of water or ammonia leads to the alkyl derivatives (Scheme 7). 

Thiazines.- Two groups have synthesised 1, 3-thiazines (360) from y-isothiocyanatoallyl chlorides (359), ring-closure being effected with primary or secondary amines or with alcohols or thiols. In the case of the thiazines (360 X=NHR), these exist as such when R = alkyl but in imino forms (361) when R = aryl.2 9 29 ... 

This reaction was initially reported by Fukuyama and co-workers in 1995. It is a two-step conversion of primary amines into secondary amines via ortho-nitrobenzenesulfonation in conjunction with the Mitsunobu Reaction and subsequent removal of the o-nitrobenzenesulfonyl group by thiophenol. Therefore, this reaction is generally known as the Fukuyama amine synthesis. In addition, it is also referred to as the Fukuyama-Mitsunobu A -alkylation," Fukuyama-Mitsunobu alkylation, Fukuyama-Mitsunobu condition, Fukuyama-Mitsunobu procedure, or Fukuyama-Mitsunobu Reaction. In this reaction, the o-nitrobenzenesulfonyl-protected amine is alkylated with alcohol in the presence of PPhs and diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD), and the deprotection occurs in a very mild condition (almost neutral ). The o-nitrobenzenesulfonyl group is simply called the Fukuyama sulfonamide protecting groupThis reaction has become a versatile method... 

In addition to the homogeneous and heterogeneous TM catalysts discussed above, other catalysts/methods such as uano catalysts, carbon materials, enzymes, chiral catalysts and continuous flow techuiques have also been developed successfully and applied in /-alkylation reactions of amines/amides with alcohols. 

Li F, Chen L, Kang Q (2013) Regioselective W-alkylation with alcohols for the preparation of 2-(N-alkylamino)quinazolines and 2-(A-aUcylamino)pyriniidines. New J Chem 37(3) 624-631 Berliner MA, Dubant SPA, Makowski T (2011) Use of an iridium-catalyzed redox-neutral alcohol-amine couphng on kilogram scale for the synthesis of a GlyTl inhibitor. Org Proc Res Deve 15(5) 1052-1062... 

Sulfonamide iV-alkylation with alcohols is an important transformation due to the abundance of the sulfonamide moiety in drugs. Traditional sulfonamide synthesis involves the reaction of a sulfonyl chloride with a primary or secondary amine. However, these methods require the use of unstable sulfonyl chlorides and generate stoichiometric salt waste. In contrast, the N-alkylation of sulfonamides with alcohols presents a convenient alternative that utilises stable starting materials and produces water as the... 

Cyanuiic chloiide is a convenient piecuisoi to alkyl oi aiyl cyanurates by reaction with alcohols or phenols, or to substituted melamines by reaction with amines alkaline conditions ate employed in both cases and yields are generally high. 

Amines can be N-alkylated by reaction with alcohols, in a sealed tube with irradiation by microwaves, with the alcohol and RuCl2(PPh3)2, or by treatment with the amine, SnCl2 and Pd(PPh3)4. Chlorodiethylaluminum (Et2AlCl), with a Cu(ll) catalysts can N-ethylate aniline derivatives. tcrt-Butylamines can be prepared from isobutylene, HBr and the amine by heating a sealed tube. ... 

Madsen and co-workers have reported an important extension to the amine alkylation chemistry, in which oxidation takes place to give the amide product [13]. A ruthenium NHC complex is formed in situ by the reaction of [RuCl Ccod)] with a phosphine and an imidazolium salt in the presence of base. Rather than returning the borrowed hydrogen, the catalyst expels two equivalents of H. For example, alcohol 31 and benzylamine 27 undergo an oxidative coupling to give amide 32 in good isolated yield (Scheme 11.7). 

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