Phthalocyanines and related compounds: XLVII. Nucleophilic replacement of chlorine atoms in tetrachlorophthalonitrile. Synthesis of phenyl(alkyl)amino-substituted phthalonitriles and some phthalocyanines based thereon

Nucleophilic replacement of chlorine atoms in tetrachlorophthalonitrile by the action of primary and secondary amines was studied. The reactions of tetrachlorophthalonitrile with amines at a ratio of 1: 10 gave with high yields and regioselectivity the corresponding 4,5-diamino-3,6-dichlorophthalonitriles from cyclic secondary amines and 4-amino-3,5,6-trichlorophthalonitriles from primary amines and acyclic secondary amines. 4-Amino-3,5,6-trichlorophthalonitriles were used to synthesize cobalt and zinc phthalocyanine complexes. It was shown that replacement of chlorine atoms in the pyrrolic β-positions of hexadecachlorophthalocyanines by amino groups is not accompanied by red shift of the long-wave absorption band in the electronic spectra.     

Versatile solid-phase synthesis of secondary amines from alcohols. Development of an N-Boc-(o-nitrobenzene)sulfonamide linker

The development of a versatile amine releasing linker based on the modified o-nitrobenzene sulfonamide protective group is described. This new N-Boc-o-nitrobenzenesulfonamide (Boc-ONBS) linker enables the elaboration on resin of primary and secondary amines by sequential substitution of the sulfonamide moiety using the Mitsunobu reaction. A 16-member array of secondary and Boc protected primary amines was then prepared using this linker.     

Acceleration of aminolysis of nitrophenyl esters by quaternized modifications of polyethylenimine

Derivatives of polyethylenimine, containing free primary amines but with secondary and tertiary amines fully quaternized, were prepared. The residual primary amines of the polymer markedly accentuated the rates of cleavage of nitrophenyl esters. This modified polymer exhibits a pK_a, determined from kinetics of its reactions, close to that for small molecules with a primary amine adjacent to a charged aminoethyl group. Thus, the primary amine group of the polymer stays relatively distant from all charged nitrogens on the macromolecule except its immediately adjacent neighbor on the chain.     

Safe and Efficient Reductive Methylation of Primary and Secondary Amines Using N-Methylpyrrolidine Zinc Borohydride

An efficient, general procedure for reductive methylation of primary and secondary amines with 37% formaldehyde using N-methylpyrrolidine zinc borohydride (ZBHNMP) as a reducing agent gave the corresponding tertiary amines in excellent yields. The reaction was carried out in tetrahydrofuran under neutral conditions at 0–10 °C.     

Optimization of normal-phase chromatographic separation of compounds with primary, secondary and tertiary amino groups

The retention behavior of primary, secondary and tertiary amines was studied using normal-phase-HPLC on silica, diol, and cyano stationary phases. Several classes of amines, including benzylamines, anilines, ephedrines, tryptamines, and azatryptamines were chromatographed using mixtures of hexane and ethoxynonafluorobutane with methylene chloride and methanol. Peak tailing, diminished selectivity and low plate count were minimized by the addition of volatile amines to the mobile phase. The optimal additive was n-propylamine at 0.1% concentration. On diol columns, the elution order of free primary, N-N-methyl, and N,N-dimethylamines was predictable, while the elution order of primary and secondary amines on cyano columns varied depending on the alcohol modifier concentration. The feasibility of preparative normal-phase chromatography was demonstrated by the separation of a mixture of primary, secondary and tertiary amines obtained by direct methylation of norephedrine. The procedures described may provide a practical alternative to traditional methods of analysis and purification of potential drug candidates.     

Selective Analysis of Secondary Amines Using Liquid Chromatography with Electrochemical Detection (LC‐EC)

In a mixture of primary and secondary aliphatic amines, the primary amines were derivatized (masked) with o‐phthalaldehyde (OPA) followed by derivatization of the remaining secondary amines with ferrocenecarboxylic acid chloride (FAC). The “tagged” amines were analyzed by LC‐EC (liquid chromatography with electrochemical detection) using in‐series dual electrode detection. Chemically‐reversible oxidation of the FAC tagged secondary amines and their subsequent complementary oxidation and reduction signals coupled with chemically‐irreversible oxidation of OPA tagged primary amines provided the selectivity for quantitative secondary amine analysis. The procedure was also applied for the selective identification of fragment 4–11 (N‐terminus‐proline) of Substance P in the presence of other Substance P fragments with primary amino acids as their N‐termini.     

Determination of low molecular weight aliphatic primary amines in urine as their benzenesulphonyl derivatives by gas chromatography with flame photometric detection.

A selective and sensitive method for the determination of low molecular weight aliphatic primary amines in urine is described. These amines were converted into their benzenesulphonyl derivatives by a modified Hinsberg procedure, and measured by gas chromatography with flame photometric detection (FPD-GC) using a DB-1 capillary column. The derivatives were very stable and provided excellent FPD responses. By FPD-GC, linear calibration curves were obtained in the range 10-200 ng of methylamine, ethylamine, n-propylamine, isobutylamine and n-butylamine using tert-butylamine as an internal standard, and the detection limits of these amines were ca. 6-25 pg as the injection amount. Benzenesulphonamide derived from ammonia was converted into its N-dimethylaminomethylene derivative which has a longer retention time, and separated from benzenesulphonyl derivatives of low molecular weight primary amines on the chromatogram. The recoveries of aliphatic primary amines added to urine samples were 91-107% and the relative standard deviations were 0.2-4.5%. Analytical results of aliphatic primary amine contents in urine samples of normal subjects are presented.     

CO2 deactivation of supported amines: does the nature of amine matter?

Adsorption of CO(2) was investigated on a series of primary, secondary, and tertiary monoamine-grafted pore-expanded mesoporous MCM-41 silicas, referred to as pMONO, sMONO, and tMONO, respectively. The pMONO adsorbent showed the highest CO(2) adsorption capacity, followed by sMONO, whereas tMONO exhibited hardly any CO(2) uptake. As for the stability in the presence of dry CO(2), we showed in a previous contribution [J. Am. Chem. Soc.2010, 132, 6312-6314] that amine-supported materials deactivate in the presence of dry CO(2) via the formation of urea linkages. Here, we showed that only primary amines suffered extensive loss in CO(2) uptake, whereas secondary and tertiary amines were stable even at temperature as high as 200 °C. The difference in the stability of primary vs secondary and tertiary amines was associated with the occurrence of isocyanate as intermediate species toward the formation of urea groups, since only primary amines can be precursors to isocyanate in the presence of CO(2). However, using a grafted propyldiethylenetriamine containing both primary and secondary amines, we demonstrated that while primary amines gave rise to isocyanate, the latter can react with either primary or secondary amines to generate di- and trisubstituted ureas, leading to deactivation of secondary amines as well.     

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.     

NMR spectroscopic investigation of multi-walled carbon nanotubes modified by amino groups

The results of the functionalization of multi-walled carbon nanotube surface by amines containing different substituents at the nitrogen atom, namely, primary n-hexylamine, secondary izadrine, and tertiary N-benzylmorpholine and dithiline, are presented. It was shown by NMR spectroscopy, thermal analysis, mass spectrometry, X-ray photoelectron spectroscopy, and elemental analysis that the interaction of primary and secondary amines with modified nanotubes results in the formation of a covalent bond with the nitrogen atom of amines, while the reactions with tertiary amines afford quaternary ammonium salts; diamine is attached covalently through both amine groups.     

Preparation of secondary and tertiary amines from nitroarenes and alcohols

Various secondary amines were obtained selectively from the reaction of nitroarenes with primary alcohols in the presence of ruthenium(II) complexes having phosphine-amine ligands as the catalyst. Secondary amines could be further alkylated with a primary alcohol using the same catalyst, but different conditions.     

Discoloration of celluloses treated with amino compounds

Degradation and discoloration of celluloses treated with different amino compounds, including primary amines and hexamethylenetetramine (HMTA), were studied using spectroscopic techniques. The colour generation was measured using standard colorimetry and the degradation and discoloration were characterized using diffuse reflectance FTIR spectroscopy and diffuse reflectance UV-visible spectroscopy. The colour of all the treated celluloses was due to the same chromophores, thus revealing that the discoloration mechanism was essentially the same. The most important reaction was the condensation between carbonyl and amino groups to form coloured imines, and secondary processes were detected at high temperatures and long heating times. The discoloration of celluloses modified with primary amines followed first-order kinetics. However, the discoloration of HMTA-treated cellulose showed an induction period which was related to the thermal decomposition of HMTA.     

Electrocatalytic Oxidation of Amines on a Mediator‐Modified Electrode by Electrochemical Copolymerization of Nitroxyl Radical Precursor Containing Pyrrole Side Chain and Bithiophene

This paper describes the electrocatalytic oxidation of amines on TEMPO (2,2,6,6‐tetramethylpiperidine‐1‐oxyl)‐modified electrodes prepared by electrochemical copolymerization of TEMPO precursor containing pyrrole side chain and 2,2′‐bithiophene. The modified electrode exhibits electrocatalytic activity for the oxidation of primary and secondary amines. Cyclic voltammetric studies showed that the peak current of the cyclic voltammogram increased linearly with increasing concentration of amine in the sample solution.     

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.     

Study of CuI catalyzed coupling reactions of aryl bromides with imidazole and aliphatic amines under microwave dielectric heating

Amination of a variety of functionalized aryl bromides with imidazole and primary and secondary amines was accomplished using a CuI/amino acid catalyst system under microwave heating. Application of microwave irradiation shortened the reaction time from 25–40 h to 6–20 min. Good to very good yields of the corresponding coupling products were obtained when imidazole and secondary amines were used as starting materials. In case of primary amines, the outcome of the reaction was dependent on the character of the substituent on aryl bromide.     

Enthalpies of formation of primary, secondary, and tertiary amineborane adducts in tetrahydrofuran solution

The enthalpies of solution of primary, secondary, and tertiary amines in THF were determined from calorimetric experiments for five primary, five secondary, and three tertiary amines. The enthalpies of formation of amineborane adducts from borane and the corresponding amines in THF solution were also determined. The differences in adduct formation enthalpies from borane and the corresponding amines can be explained by taking into account steric effects and the chain length of the substituents on the amine. In general, as the alkyl chain length, branching, or the number of chains increases, the formation enthalpy of amineborane adducts is less exothermic. That is to say, the steric effect is more important in tertiary and secondary amines than in primary ones. The enthalpy of solution of linear primary amines in THF was more endothermic as the alkyl chain increased and a similar behavior was observed with linear secondary and tertiary ones. An analysis is made of the amine structural factors which affect the amineborane adduct formation.     

A diastereoselective and general route to 5-amino-5-deoxysugars: influence of C-3 substitution on the addition of amines to C-5 of vinyl sulfone-modified hex-5-enofuranosyl carbohydrates

In the synthesis of vinyl sulfone-modified hex-5-enofuranosides, the E/Z ratios of the products are influenced by the stereoelectronic property of a group present at the C-3 position. This observation has been utilized to influence the diastereoselectivity of addition of amines to C-5 of vinyl sulfone- modified hex-5-enofuranosides, which are efficient Michael acceptors. The stereoelectronic effect of OMe attached to the beta-face of C-3 (gluco derivative) is sufficient to impose diastereoselectivity overwhelmingly in favor of l-ido-aminosugars when the Michael acceptor is reacted with both primary and secondary amines. 3-O-Benzylated gluco derivative is also effective in producing l-ido-aminosugars but only in reactions with primary amines. The selectivity is lost when an allo derivative with OBn at the alpha-face of C-3 is used. Selected products were desulfonated to establish this new approach as a general and versatile strategy for accessing 5-amino-5-deoxysugars.     

Amberlite IRA-400 Cl resin catalyzed synthesis of secondary amines and transformation into N-((1H-indol-3-yl) (heteroaryl) methyl)-N-heteroaryl benzenamines and bis-indoles via multicomponent reaction

A one-pot Amberlite IRA-400 Cl resin catalyzed the in-situ generation of imines from various aldehydes and primary amines followed by reduction with sodium borohydride affording corresponding secondary amines. The secondary amines thus obtained were utilized for the IRA-400 Cl resin catalyzed multicomponent synthesis of 3-aminoalkylated indoles using a number of aldehydes and indole. Mild condition, easy work-up, and environmentally benign nature of the synthetic strategy make it both practical and attractive.     

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.     

Three-component one-pot process to propargylic amines and related amide and sulfonamide compounds: application to the construction of 2-(aminomethyl)benzofurans and indoles

An efficient palladium-copper-catalyzed three-component assembling of propargyl halides, aryl or heteroaryl halides, and secondary amines is described. A wide variety of tertiary propargylic amines were synthesized in good to excellent yields from easily accessible starting materials. This three-component assembling was also effective when using potassium phthalimide or di-tert-butyliminodicarbonate instead of secondary amines. Consequently, it provides a quick entry to N-protected propargylic amines suitable intermediates for the synthesis of primary and secondary propargylic amines. In a similar way, related compounds including propargylic amide, carbamate and sulfonamide derivatives were efficiently obtained. This catalytic domino three-component process has been applied successfully to the construction of functionalized 2-(aminomethyl)benzo[b]furan or indole derivatives of biological interest.