Selective N-alkylation of amines using nitriles under hydrogenation conditions: facile synthesis of secondary and tertiary amines

Nitriles were found to be highly effective alkylating reagents for the selective N-alkylation of amines under catalytic hydrogenation conditions. For the aromatic primary amines, the corresponding secondary amines were selectively obtained under Pd/C-catalyzed hydrogenation conditions. Although the use of electron poor aromatic amines or bulky nitriles showed a lower reactivity toward the reductive alkylation, the addition of NH(4)OAc enhanced the reactivity to give secondary aromatic amines in good to excellent yields. Under the same reaction conditions, aromatic nitro compounds instead of the aromatic primary amines could be directly transformed into secondary amines via a domino reaction involving the one-pot hydrogenation of the nitro group and the reductive alkylation of the amines. While aliphatic amines were effectively converted to the corresponding tertiary amines under Pd/C-catalyzed conditions, Rh/C was a highly effective catalyst for the N-monoalkylation of aliphatic primary amines without over-alkylation to the tertiary amines. Furthermore, the combination of the Rh/C-catalyzed N-monoalkylation of the aliphatic primary amines and additional Pd/C-catalyzed alkylation of the resulting secondary aliphatic amines could selectively prepare aliphatic tertiary amines possessing three different alkyl groups. According to the mechanistic studies, it seems reasonable to conclude that nitriles were reduced to aldimines before the nucleophilic attack of the amine during the first step of the reaction.     

Chemoselective organocatalytic aerobic oxidation of primary amines to secondary imines

Biomimetic aerobic oxidation of primary benzylic amines has been achieved by using a quinone catalyst. Excellent selectivity is observed for primary, unbranched benzylic amines relative to secondary/tertiary amines, branched benzylic amines, and aliphatic amines. The exquisite selectivity for benzylic amines enables oxidative self-sorting within dynamic mixtures of amines and imines to afford high yields of cross-coupled imine products.     

Cesium effect: high chemoselectivity in direct N-alkylation of amines

A novel method for the mono-N-alkylation of primary amines, diamines, and polyamines was developed using cesium bases in order to prepare secondary amines efficiently. A cesium base not only promoted alkylation of primary amines but also suppressed overalkylations of the produced secondary amines. Various amines, alkyl bromides, and alkyl sulfonates were examined, and the results demonstrated this methodology was highly chemoselective to favor mono-N-alkylation over dialkylation. In particular, use of either sterically demanding substrates or amino acid derivatives afforded the secondary amines exclusively, offering wide applications in peptidomimetic syntheses.     

General and efficient synthesis of arylamino- and alkylamino-substituted diphenylporphyrins and tetraphenylporphyrins via palladium-catalyzed multiple amination reactions

A series of arylamino- and alkylamino-substituted diphenylporphyrins and tetraphenylporphyrins were efficiently synthesized by reactions of brominated porphyrin precursors with amines via palladium-catalyzed amination. The multiple amination reactions are general and suitable for a variety of amines, affording the desired aminoporphyrins in good to excellent yields. Examples include aromatic and aliphatic amines, primary and secondary amines, electron-rich, -neutral, and -poor amines as well as heteroaromatic amines and imines.     

胺及其衍生物的非酰基化动力学拆分

光学纯胺在合成与药物化学领域都有着广泛的应用,发展其高效的合成方法一直以来是有机化学界的研究热点.其中通过N酰基化及去酰基化动力学拆分方法获得光学纯胺化合物,已经成为合成手性胺类化合物的重要方法.近年来,基于非酰基化(或去酰基化)的不对称反应实现外消旋胺的动力学拆分的报道不断涌现,包括一些氨基不参与反应的非酰基化(或去酰基化)不对称反应的外消旋胺的动力学拆分.根据氮原子是否参与反应以及反应类型的不同,总结了外消旋胺的化学催化动力学拆分的研究进展.     

Thermometric titrations of amines with nitrosyl perchlorate in acetonitrile solvent

Thirteen aliphatic and four aromatic amines, namely diethylamine, triethylamine, n-propylamine, di-n-propylamine, tri-n-butylamine, isopropylamine, di-isopropylamine, n-butylamine, di-n-butylamine, tri-n-butylamine, isobutylamine, sec-butylamine, tert-butylamine, aniline, N,N-dimethylaniline, 2-nitroaniline and 4-nitroaniline were titrated thermometrically with nitrosyl perchlorate in acetonitrile solvent. All the aliphatic amines gave very well-shaped thermometric titration curves. The calculated recovery values of the amines were very good. In comparison, the aromatic amines, aniline and N,N-dimethylaniline gave rather well-shaped titration curves, but the recovery values were fairly low. 2-Nitro- and 4-nitro anilines gave no thermometric response at all. The heats of reaction of the amines with nitrosyl perchlorate are rather high. However, the average heat of reaction of the aromatic amines is approximately two-thirds that of the average heat of the aliphatic amines. To support this method all the amines were also titrated potentiometrically and very similar results to those obtained with the thermometric method are seen. The nitrosyl ion is a Lewis acid, strong enough to titrate quantitatively aliphatic amines in acetonitrile solvent, but not strong enough to titrate aromatic amines at the required level in the same solvent.     

Development of a General Non‐Noble Metal Catalyst for the Benign Amination of Alcohols with Amines and Ammonia

The N‐alkylation of amines or ammonia with alcohols is a valuable route for the synthesis of N‐alkyl amines. However, as a potentially clean and economic choice for N‐alkyl amine synthesis, non‐noble metal catalysts with high activity and good selectivity are rarely reported. Normally, they are severely limited due to low activity and poor generality. Herein, a simple NiCuFeO_x catalyst was designed and prepared for the N‐alkylation of ammonia or amines with alcohol or primary amines. N‐alkyl amines with various structures were successfully synthesized in moderate to excellent yields in the absence of organic ligands and bases. Typically, primary amines could be efficiently transformed into secondary amines and N‐heterocyclic compounds, and secondary amines could be N‐alkylated to synthesize tertiary amines. Note that primary and secondary amines could be produced through a one‐pot reaction of ammonia and alcohols. In addition to excellent catalytic performance, the catalyst itself possesses outstanding superiority, that is, it is air and moisture stable. Moreover, the magnetic property of this catalyst makes it easily separable from the reaction mixture and it could be recovered and reused for several runs without obvious deactivation.     

Direct N-alkylation of amines with alcohols using AlCl3 as a Lewis acid

A substitution reaction of amines with alcohols for N-alkylated amines has been developed using inexpensive AlCl_3 without any ligand or additive.Either aromatic or aliphatic amines and primary or secondary alcohols perform the AlCl_3-mediated reaction smoothly to afford various N-alkylated amines in satisfactory yields.     

Blue Chitin Columns for the Extraction of Heterocyclic Amines from Urine Samples

During normal cooking of meat, a class of mutagenic/carcinogenic compounds called heterocyclic amines is formed. Heterocyclic amines are rapidly absorbed and metabolised in the human body, and for estimation of the intake of heterocyclic amines, it is useful to determinate their levels in the urine. Blue Chitin columns were used for the extraction and purification of heterocyclic amines from urine samples spiked with 14 different heterocyclic amines. The samples were analysed using LC-MS. The results show that Blue Chitin columns provide a straightforward and rapid means of extracting heterocyclic amines from urine samples, and that Blue Chitin column are also useful in the purification of urinary metabolites.     

伯胺的单烷基化反应研究进展

伯胺的单烷基化在有机合成过程中是非常重要的一类反应。由于伯胺的化学性质较活泼,对其进行烷基化时很难控制在仲胺阶段而易于生成叔胺,因而其单烷基化一般通过间接的方法得到。本文介绍了伯胺单烷基化方法的最新研究进展。     

Diastereoselective addition of amines to vinyl sulfone modified carbohydrates: a highly flexible methodology for the synthesis of new classes of deoxyaminosugars

Methyl 2,3-dideoxy-4,6-O-(phenylmethylene)-3-C-phenylsulfonyl-alpha- D-erythro-hex-2-enopyranoside (5 alpha) and methyl 2,3-dideoxy-4,6-O-(phenylmethylene)-3-C-phenylsulfonyl- beta-D-erythro-hex-2-enopyranoside (5 beta) have been subjected to Michael addition reaction with various amines to develop a new methodology for the synthesis of new classes of aminosugars. Compound 5 alpha reacted with primary amines to generate gluco- derivatives, but secondary amines produced both gluco- (major) and manno- (minor) isomers. Compound 5 beta, on the other hand, produced only gluco- isomers with both primary and secondary amines. The stereochemical course of addition of some of the amines to 5 alpha and 5 beta are significantly different from that of the addition of amines to 3-nitroenopyranoses. The present route to the syntheses of various aminosugars with gluco- configurations from 5 alpha and 5 beta constitutes a novel method for the introduction of N-monoalkylated and N,N-dialkylated amines to the C-2 carbon of pyranoses in equatorial configurations.     

Colloid and nanosized catalysts in organic synthesis: XIV. Reductive amination and amidation of carbonitriles catalyzed by nickel nanoparticles

Hydrogenation of carbonitriles catalyzed by nickel nanoparticles in the presence of primary amines led to the predominant formation of unsymmetrical secondary amines. In the presence of secondary amines hydrogenation of nitrites provided enamines as main products. Hydrogenation of nitriles in the presence of formamide or acetamide afforded formyl or acetyl derivatives of primary amines.     

AlMe(3)-promoted formation of amides from acids and amines

In the presence of AlMe(3), amines can be directly coupled with acids through dimethylaluminum amide intermediates to form the corresponding amides. A wide range of amines and acids including less nucleophilic amines, bulky amines, unprotected secondary amino acids, and acids with poor solubility were coupled smoothly to give the desired products in 55-98% yields.     

三级胺及酰胺硝解研究进展

综述了三级叔胺及酰胺硝解的近期研究进展,重点是已作为或有可能成为高能量密度化合物硝胺的合成。讨论了三级胺及酰胺的硝解历程,汇集了常用的硝化及硝解系统。详细阐述了烷基叔胺、叔酰胺、烷基酰基叔胺。特别是多环笼形叔胺和叔酰胺的硝解反应及硝解条件。     

Efficient synthesis of tertiary amines from secondary amines

Reliable N-alkylations of secondary amines have been developed. By using DIAD and TPP (or PS-TPP) a variety of secondary amines can be converted to the corresponding tertiary amines in good to excellent yields with diverse alkylhalides; no formation of quaternary amine salts are observed. These protocols are amenable to combinatorial chemistry libraries, and are also useful for the syntheses of secondary amines by an acid lysis of the cleavable tertiary amino resins.     

Fluorogenic imines for fluorescent detection of Mannich-type reactions of phenols in water

Fluorogenic imines and their precursor amines that can be used for fluorescent visualization of Mannich-type reactions of phenols in aqueous buffers have been developed. The precursor amines are aniline derivatives that are covalently conjugated to fluorophores. These amines and their imine derivatives were nonfluorescent or very weakly fluorescent. On the other hand, addition products of the imines to phenols showed more than 100-fold higher fluorescence than the imines and the precursor amines.     

Factors affecting the efficiency and stereoselectivity of α-amino acid synthesis by the Petasis reaction

The use of chiral secondary amines containing only one branched substituent has been shown to give optimal yields and stereoselectivities in the preparation of α-amino acids using the Petasis reaction. While the use of chiral primary amines generally gives products in low to moderate diastereoselectivity, chiral secondary amines generally give products in >95:5 diastereoselectivity. Additionally, the use of amines with two chiral (and by definition, branched) N-alkyl substituents results in significantly reduced yields with respect to to secondary amines with one or no branched N-alkyl substituents.     

Chemospecific and ligand free CuI catalysed heterogeneous N-arylation of amines with diheteroaryl halides at room temperature

A ligand free, copper-catalyzed N-arylation reaction of amines with diheteroaryl halides in heterogeneous medium at room temperature has been developed. The protocol is very effective for low boiling amines and useful for amines available in aqueous solution. The reaction gives chemospecific arylation of amines with diheteroaryl halides in the mixture monoheteroaryl halides, diheteroaryl halides and carbocyclic aryl halides. The reaction is also chemospecific with respect to arylation of aliphatic amines. Monoarylated piperazines were also synthesized at room temperature following this protocol.     

二级胺与羰基化合物的一步还原烷基化

碲试剂作为还原剂已得到较广泛的应用,Yamashita、周洵钧将NaHTe用于羰基化合物还原胺化为二级胺,Kambe等近期用H_2Te还原烯胺、亚胺到相应的胺,我们曾用NaHTe将二级胺与羰基化合物还原烷基化。本文采用不同二级胺进一步研究发现,脂肪环胺与醛的反应效果较好,同一条件下烯胺也可被还原,反应条件温和,脯氨酸酯还原烷基化的产物不发生明显消旋化(表1,3),可应用于氨基酸类反应。     

Grafting onto wool. VIII. Graft copolymerization of methyl methacrylate (MMA) by use of Ce4+ -amine system as redox initiator

In an attempt to determine the role of a variety of amines in ceric-ion-initiated grafting, poly-(methyl methacrylate) was graft copolymerized onto Himachali wool in the presence of a variety of amines that included ammonia, diethylamine (DEA), dipropylamine (DPA), triethylamine (TEA), triethanol amine, and pyridine. All amines (with the exception of DEA) reduced the percent grafting. The reactivity of various amines toward graft copolymerization followed the order: DEA > DPA > NH₃ > TEA > triethanol amine > Py. An explanation based on the basicity, nucleophilicity, and steric requirement of amines is given to explain the observed reactivity order shown by the various amines toward graft copolymerization.