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.     

Reactions of the carbonate radical with aliphatic amines

Carbonate radicals react with aliphatic amines by a dual mechanism, viz. (i) hydrogen abstraction and (ii) electron transfer. The former is more probable with primary amines. Tertiary amines react via electron transfer. Both mechanisms may operate in secondary amines. Cyclic tertiary amines react with different rates and their relative reactivities are explained on the basis of the concept of Hoffmann's ‘through bond’ interaction.     

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.     

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.     

多相双金属Pt-Sn/γ-Al_2O_3催化的胺N-烷基化反应合成仲胺和叔胺

基于借氢策略、醇为烷基化试剂的胺的N-烷基化反应是合成胺类化合物的绿色途径.在无外加氢源条件下,多相双金属Pt-Sn/γ-Al2O3催化剂可高效催化醇为烷基化试剂的伯(仲)胺的N-烷基化反应合成仲(叔)胺,反应副产物为水与极少量亚胺.催化体系的底物适应性好,目标产物收率高;催化剂可以循环使用,具有潜在的工业化应用前景.     

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.     

Hydrogen bonding by alcohols and amines

The pure base calorimetric method has been used to determine the enthalpies of hydrogen bond complex formation between aliphatic amines and alcohols. The enthalpies of complexation for the series methanol-n-butanol bonding with triethylamine increase with decreasing alkyl chain length in accordance with the electron donating properties of alkyl groups. Unexpectedly, the enthalpies for the complexes of n-butanol with tributylamine, tripropylamine, and triethylamine increase with decreasing alkyl chain length.Primary and secondary amines form hydrogen bonded complexes with n-butanol in which the amine protons form an NH···O bond with the alcohol and the alcohol hydroxyl proton donates a proton to the amine nitrogen. The difference in enthalpy of complex formation between tertiary amines and secondary amines is largely accounted for by the involvement of the amine proton of the secondary amine. Primary amines, like secondary amines, donate only one proton to the complex with n-butanol but have a larger complex enthalpy than secondary amines probably because of steric hindrance and differences in basicity.     

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.     

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.     

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.     

Oxidative amide synthesis directly from alcohols with amines

Transition metal catalyzed oxidative amide synthesis directly from primary alcohols and amines is a highly atom economical transformation that evolves hydrogen gas as the only by-product. Several Ru-, Rh-based homogeneous and Ag-based heterogeneous catalysts have been developed for direct amide synthesis. Most of the developed catalysts showed excellent activity with sterically unhindered alcohols and amines; however, limited activity was observed with sterically hindered alcohols or amines, less basic aryl amines, and secondary amines. This account provides an overview of recent advances and challenges in direct amide synthesis.     

Selective synthesis of secondary and tertiary amines by cp*iridium-catalyzed multialkylation of ammonium salts with alcohols

The efficient selective synthesis of secondary and tertiary amines has been achieved by means of Cp*Ir-catalyzed multialkylation of ammonium salts with alcohols without solvent: the reactions of ammonium acetate with alcohols gave tertiary amines exclusively, while those of ammonium tetrafluoroborate afforded secondary amines selectively. Using this method, secondary 5- and 6-membered cyclic amines were synthesized from ammonium tetrafluoroborate and diols in one pot.     

Palladium-catalyzed reaction of allyl carbamates; allylation of carbonucleophiles,and protection-deprotection of amines

Allylation of carbonucleophiles with allylic carbamates under neutral conditions has been studied. The C-allylation of carbonucleophile is competitive with the N-allylation of amines, and the structure of amines is crucial for the selectivity. Bulky secondary amines gave the best results. Also a new method of protection-deprotection of amines as carbamates has been developed. Smooth deprotection is possible by the palladium-catalyzed reaction of allyl carbamates with formic acid. This method is particulary useful for primary amines, including optically active amino acids.     

Facile N‐Alkylation/N′‐Arylation Process: A Direct Approach to Aromatic Aminoalkyl Amines

An intriguing C?N transformation involving a catalyst‐free N‐alkylation/N′‐arylation process in a multicomponent reaction with secondary amines, cyclic tertiary amines and electron‐deficient aryl halides has been described. In this case, the N‐alkylation of secondary amines, utilizing cyclic tertiary amines as alkyl group sources, is enabled by a facile C?N cleavage. Such an operationally simple method could facilitate access to aromatic aminoalkyl amines, nitrogen‐containing bioactive molecules, in good to excellent yields.     

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.     

Solution-phase library synthesis of furanoses

The solution-phase synthesis of amido-, urea-, and aminofuranoses was achieved. Alkylated furanose aldehydes were treated with primary amines in the presence of sodium triacetoxyborohydride to give secondary amines. Subsequent acylation with acid chlorides and isocyanates afforded amidofuranoses and ureafuranoses, respectively. Second, reductive amination of furanose aldehydes with secondary amines yielded tertiary amines. The resulting acetonides were treated with alcohols in the presence of acid to yield mixed acetals. In the library syntheses, functionalized scavenger resins were used in the purification of intermediates and products.     

Fast naked-eye detection of amines with viologen derivatives

Three viologen derivatives with the ability to detect amines were synthesised. Upon interacting with amines, a rapid colour change caused by electron transfer and charge transfer between viologen derivatives and amines can be directly observed by naked eyes. With fluorine substituents, the detection sensitivity of these viologen derivatives for amines is remarkably enhanced to reach the level of ppm.     

Fluorometric sensing of biogenic amines with aggregation-induced emission-active tetraphenylethenes

A fluorometric sensor for detection and identification of biogenic amines with carboxylic acid modified tetraphenylethenes (TPEs) based on aggregation-induced emission (AIE) is reported. A mixture of the carboxylic acid substituted TPE and biogenic amines displayed a blue emission on aggregation, which serves as a "turn-on" fluorescent sensor for the amines, the degree of fluorescence enhancement being dependent on the amine. The chromic responses were utilized to distinguish the amines. A fluorometric sensor array of three TPEs with carboxylic acid groups was shown to identify accurately 10 different amines, including biogenic amines. The response patterns were systematically classified by using linear discriminant analysis (LDA) with 98% classification accuracy. Additional information on the concentration of histamine in a "tuna fish matrix" as an example was assessed by the further analysis of the fluorescence intensity, demonstrating a test for food freshness and quality.