Thermodynamic study of heptane + secondary, tertiary and cyclic amines mixtures. Part IV. Excess and solvation enthalpies at 298.15 K

Partial molar enthalpies and excess enthalpies H^E of binary mixtures of heptane + secondary and tertiary n-alkyl, primary cycloalkyl, and secondary (hetero)cyclic amines have been determined at 298.15 K by isothermal titration calorimetry in the whole composition range. All mixtures showed positive H^E values which decrease with increasing amine size in each category, and decrease in the order cyclic primary > cyclic secondary > linear primary [1] > secondary > tertiary when comparing amines of similar size in different categories. From partial molar enthalpies at infinite dilution and known enthalpies of vaporization, the solvation enthalpies have been calculated either for heptane in amines and for amines in heptane. These quantities, together with their cavitational and interactional terms obtained applying the scaled particle theory, are discussed to get insight into the types and relative strength of solute-solvent interactions and into their effects on molecular structure features such as branching and cyclization.     

Deallyloxy- and debenzyloxycarbonylation of protected alcohols, amines and thiols via a naphthalene-catalysed lithiation reaction

The naphthalene-catalysed lithiation of Alloc- and Cbz-protected alcohols, amines and thiols in THF at 0 °C led, after quenching with methanol, to the recovery of the free alcohols, amines and thiols in short reaction times and with very good yields. The selectivity for the removal of the Alloc- or the Cbz- group in a polyfunctionalised substrate has been studied. The selective reductive cleavage of a benzylic carbon-oxygen bond was achieved in the presence of an allylic carbon-oxygen or carbon-nitrogen bond. This method represents a great improvement in comparison with the previously reported deprotection procedures by dissolving metals, since it avoids the use of the toxic liquid ammonia and, therefore, the need to perform the reaction at low temperatures.     

Enantioselective Oxidative Aerobic Dealkylation of N‐Ethyl Benzylisoquinolines by Employing the Berberine Bridge Enzyme

N‐Dealkylation methods are well described for organic chemistry and the reaction is known in nature and drug metabolism; however, to our knowledge, enantioselective N‐dealkylation has not been yet reported. In this study, exclusively the (S)‐enantiomers of racemic N‐ethyl tertiary amines (1‐benzyl‐N‐ethyl‐1,2,3,4‐tetrahydroisoquinolines) were dealkylated to give the corresponding secondary (S)‐amines in an enantioselective fashion at the expense of molecular oxygen. The reaction is catalyzed by the berberine bridge enzyme, which is known for C? C bond formation. The dealkylation was demonstrated on a 100 mg scale and gave optically pure dealkylated products (ee>99 %).     

A novel salt-free ruthenium-catalyzed alkylation of aryl amines

The alkylation of aryl amines using cyclic amines such as pyrrolidine proceeds via borrowing hydrogen methodology in the presence of 1 mol % Shvo catalyst. During the reaction multiple carbon-nitrogen cleavage and formation occurred. This novel reaction sequence leads to N-aryl-pyrrolidines and -piperidines.     

Multicomponent Reactions with Cyclic Tertiary Amines Enabled by Facile C−N Bond Cleavage

A novel and catalyst‐free multicomponent reaction with cyclic tertiary amines, electron‐deficient aryl halides or heteroaromatic halides, and Na₂S enabled by facile C−N bond cleavage of the cyclic tertiary amines was developed. This direct and operationally simple method can be applied with a wide range of functional groups and provides an efficient and rapid approach to potentially drug‐like products containing amine, azaarene, thioether, or phenol ether functionalities in good to excellent yields. The utility of this method was demonstrated by the rapid synthesis of the analgesic ruzadolane.     

CpIr-catalyzed N-alkylation of amines with alcohols. A versatile and atom economical method for the synthesis of amines

A versatile and highly atom economical catalytic system consisting of [Cp^∗IrCl₂]₂/NaHCO₃ (Cp^∗=pentamethylcyclopentadienyl) for the N-alkylation of amines with primary and secondary alcohols as alkylating reagents has been developed. For example, the reaction of equimolar amounts of aniline and benzyl alcohol in the presence of [Cp^∗IrCl₂]₂ (1.0 mol % Ir) and NaHCO₃ (1.0 mol %) in toluene at 110 °C gives N-benzylaniline in 94% yield. The present catalytic system is applicable to the N-alkylation of both primary and secondary amines, and only harmless water is produced as co-product. A wide variety of secondary and tertiary amines can be synthesized with high atom economy under mild and less-toxic conditions. One-pot sequential N-alkylation leading to tertiary amines bearing three different substituents is also described.     

Unexpected reactions of [60]fullerene involving tertiary amines and insight into the reaction mechanisms

Thermal reactions of [60]fullerene with amino acid ester hydrochlorides and triethylamine in o-dichlorobenzene at reflux afforded pyrrolidinofullerene derivatives containing the CH(3)CH moiety and originating from triethylamine through an unusual C-N bond cleavage. Detailed investigation of these thermal reactions resulted in the discovery of unprecedented reactions between C(60) and tertiary amines and of reactions of C(60) with tertiary amines and aldehydes, giving cyclopentafullerene derivatives with high stereoselectivity. Plausible reaction mechanisms for the product formation involving the uncommon C-N bond cleavage of tertiary amines were proposed on the basis of extensive experimental results.     

Copper‐Catalyzed Aerobic Oxidative Inert CC and CN Bond Cleavage: A New Strategy for the Synthesis of Tertiary Amides

A copper‐catalyzed aerobic oxidative amidation reaction of inert C?C bonds with tertiary amines has been developed for the synthesis of tertiary amides, which are significant units in many natural products, pharmaceuticals, and fine chemicals. This method combines C?C bond activation, C?N bond cleavage, and C?H bond oxygenation in a one‐pot protocol, using molecular oxygen as the sole oxidant without any additional ligands.     

‘Counter-intuitive’ regioselectivity, subtle steric and solvation effects in lithiation of cyclic tertiary aralkylamines

Lithiation of a series of cyclic aralkyl tertiary amines with sec-BuLi in various solvents has been studied. There is a subtle sensitivity to steric factors and lithium coordinating solvents/additives have an adverse effect. ortho-Lithiation is observed only in the case of an eight-membered cyclic amine and the ease of benzylic lithiation with respect to nitrogen is in the surprising order γ > β ? α, δ. These observations are discussed in the context of nitrogen coordination promoted lithiation.     

Hydrolysis of the amide bond in N-acetylated l-methionylglycine catalyzed by various platinum(II) complexes under physiologically relevant conditions

The hydrolytic reactions between various Pt(II) complexes of the type [Pt(L)Cl₂] and [Pt(L)(CBDCA-O,O′] (L is ethylenediamine, en; (±)-trans-1,2-diaminocyclohexane, dach; (±)-1,2-propylenediamine, 1,2-pn and CBDCA is the 1,1-cyclobutanedicarboxylic anion) and the N-acetylated l-methionylglycine dipeptide (MeCOMet-Gly) were studied by ¹H NMR spectroscopy. All reactions were realized at 37 °C with equimolar amounts of the Pt(II) complex and the dipeptide at pH 7.40 in 50 mM phosphate buffer in D₂O. Under these experimental conditions, a very slow cleavage of the Met-Gly amide bond was observed and this hydrolytic reaction proceeds through the intermediate [Pt(L)(H₂O)(MeCOMet-Gly-S)]⁺ complex. In general, it can be concluded that faster hydrolytic cleavage of the MeCOMet-Gly dipeptide was observed in the reaction with the chloride complex than with corresponding CBDCA Pt(II) complexes. The steric effects of the Pt(II) complex on the hydrolytic cleavage of the amide bond in the MeCOMet-Gly dipeptide were also investigated by ¹H NMR spectroscopy. It was found that the rate of hydrolysis decreases as the steric bulk of the CBDCA and chlorido Pt(II) complexes increase (en > 1,2-pn > dach). These results contribute to a better understanding of the toxic side effects of Pt(II) antitumor drugs and should be taken into consideration when designing new potential Pt(II) antitumor drugs with preferably low toxic side effects.     

Practical Catalytic Cleavage of C(sp3)−C(sp3) Bonds in Amines

The selective cleavage of thermodynamically stable C(sp³)?C(sp³) single bonds is rare compared to their ubiquitous formation. Herein, we describe a general methodology for such transformations using homogeneous copper‐based catalysts in the presence of air. The utility of this novel methodology is demonstrated for C_α?C_β bond scission in >70 amines with excellent functional group tolerance. This transformation establishes tertiary amines as a general synthon for amides and provides valuable possibilities for their scalable functionalization in, for example, natural products and bioactive molecules.     

Liquid-phase microextraction and GC for the determination of primary, secondary and tertiary aromatic amines as their iodo-derivatives

Presence of iodine in aromatic amines, introduced by their reaction with iodine, and other electron withdrawing substituents such as chlorine and nitro, has been found to afford excellent liquid-phase microextraction (LPME) in toluene and separation by gas chromatography in the determination of primary, secondary and tertiary aromatic amines. The effect is due to decreased basic nature of amines when electronegative substituents are present. Single drop microextraction (SDME) of the amines in 2 μl of toluene and injection of the whole extract into GC, or LPME into 50 μl of toluene and injection of 2 μl of extract, were used. LPME has been found more robust and to give better extraction in shorter period than SDME. In SDME-GC-FID, the average correlation coefficient was 0.9939 and average limit of detection 25 μg l⁻¹ (range 12-61 μg l⁻¹) whereas the corresponding values in LPME-GC-MS were, respectively, 0.9953 and 33 ng l⁻¹ (range 18-60 ng l⁻¹). The method has been applied to determine aromatic amines in river water, dye factory effluents and food dye stuffs. The LPME was found as robust, rugged and simple extraction method.     

Chitosan/carboxymethyl cashew gum polyelectrolyte complex: synthesis and thermal stability

Chitosan/carboxymethyl cashew gum polyelectrolyte complexes were synthesized using different proportions of chitosan (CH) and carboxymethyl cashew gum (CMCG). The optimum CH:CMCG ratio was 25:75, which produced highest product yield. Polyelectrolyte (PEC) samples were characterized by thermogravimetric analysis and FT-IR spectroscopy. Parameters such as initial and maximal degradation temperatures and activation energy (E_a) were determined. Activation energies follows the order CMCG > CH > PECs samples. Infrared analysis from residual products after heating at 280 °C in different times indicated that cleavage of the glycosidic bond and formation of unsaturated products occurred.     

锆氢催化的酰胺硼氢化合成胺类化合物研究:机理、使用范围和应用

发展温和条件下胺类化合物的高效合成方法是催化与合成领域长期研究的课题.其中,酰胺还原因其原料来源广、易于合成而广受关注.酰胺还原到胺需要选择性断裂C=O键,因此该反应具有很大的挑战性.传统酰胺还原方法需要使用当量的强还原试剂,如四氢铝锂、硼氢化钠等,且官能团兼容性较差.使用氢气还原原子经济性最高,也最有吸引力;然而,目前已报道的体系大都在高温(>120℃)或高压(>40 bar H2)的条件下进行.虽然催化硼氢化可以在温和的条件下将羰基化合物还原,但由于酰胺化合物惰性比较高,其选择性的催化硼氢化研究则相对较少,而且在温和条件下对三级、二级、一级酰胺都适用的例子依然非常有限.本文采用前过渡金属锆氢催化剂实现了室温条件下酰胺选择性硼氢化制备胺类化合物,并进行了详细的机理研究.原位红外监测到反应过程中酰胺和硼烷逐渐减少,目标产物逐渐增多;但并未给出其他反应中间体的信息.核磁研究以及对照实验结果表明,反应中有苯甲醛的生成,可能是反应中间体.因此推测,该催化体系经历了锆氢介导的酰胺C?N键断裂、重组、C?O键断裂这一特殊的酰胺键活化转化过程.DFT计算也证实了上述反应历程的可行性.除一些常见官能团外,本方法对羧酸酯、氰基、硝基、烯烃和炔烃这些可能被硼氢化的官能团同样具有兼容性.而且本文体系对一些生物、药物分子衍生酰胺的硼氢化也可以顺利进行.可见,本文发展了一种温和条件下使用廉价催化剂和原料选择性合成胺类化合物的方法.     

锆氢催化的酰胺硼氢化合成胺类化合物研究:机理、使用范围和应用

发展温和条件下胺类化合物的高效合成方法是催化与合成领域长期研究的课题.其中,酰胺还原因其原料来源广、易于合成而广受关注.酰胺还原到胺需要选择性断裂C=O键,因此该反应具有很大的挑战性.传统酰胺还原方法需要使用当量的强还原试剂,如四氢铝锂、硼氢化钠等,且官能团兼容性较差.使用氢气还原原子经济性最高,也最有吸引力;然而,目前已报道的体系大都在高温(>120℃)或高压(>40 bar H2)的条件下进行.虽然催化硼氢化可以在温和的条件下将羰基化合物还原,但由于酰胺化合物惰性比较高,其选择性的催化硼氢化研究则相对较少,而且在温和条件下对三级、二级、一级酰胺都适用的例子依然非常有限.本文采用前过渡金属锆氢催化剂实现了室温条件下酰胺选择性硼氢化制备胺类化合物,并进行了详细的机理研究.原位红外监测到反应过程中酰胺和硼烷逐渐减少,目标产物逐渐增多;但并未给出其他反应中间体的信息.核磁研究以及对照实验结果表明,反应中有苯甲醛的生成,可能是反应中间体.因此推测,该催化体系经历了锆氢介导的酰胺C?N键断裂、重组、C?O键断裂这一特殊的酰胺键活化转化过程.DFT计算也证实了上述反应历程的可行性.除一些常见官能团外,本方法对羧酸酯、氰基、硝基、烯烃和炔烃这些可能被硼氢化的官能团同样具有兼容性.而且本文体系对一些生物、药物分子衍生酰胺的硼氢化也可以顺利进行.可见,本文发展了一种温和条件下使用廉价催化剂和原料选择性合成胺类化合物的方法.     

Synthesis and solid state structures of tri-t-butyl-cyclopropenyl derivatives of main group elements: Cyp*MPh3 (M = Si, Ge, Sn)

The reaction of Ph₃MLi (M = Si, Ge, and Sn) with tri-t-butylcyclopropenium tetrafluoroborate gives the cyclopropenyl compounds Cyp*MPh₃ as air and moisture stable solids in 11%, 74%, and 77% yields, respectively. Attempts to prepare Cyp*PbPh₃ by this method were unsuccessful. The X-ray crystal structures of all three of these compounds were obtained. The M-C(Cyp*) bond distances increase with the order: Sn-C (2.19 Å) > Ge-C (2.00 Å) > Si-C (1.91 Å). A high degree of steric strain is evidenced for the silicon derivative which forms an exocyclic bond angle (Si-C(Cyp*)-C(^tBu)) of 121.6°. The high degree of steric strain for the silicon analog is believed to be responsible for the low yields for its synthesis.     

Ligand-free C–N bond formation in aqueous medium using a reusable Cu–Mn bimetallic catalyst

A general ligand-free protocol has been described for the recyclable and reusable Cu–Mn catalyzed C–N bond forming cross coupling reaction of arylboronic acids with various amines to form N-arylated amine products in aqueous medium affording excellent yields under ambient conditions, in 3–4 h.     

Poly(urethaneimides) (PUIs) containing tertiary amine groups as precursors for original PUI cationomers

This paper details the synthesis and characterisation of poly(urethaneimides) (PUIs) containing tertiary amine groups and obtained from a polytetramethylene oxide diol (PTMO1000), N-methyldiethanolamine (MDEA), 4,4′-methylene-bis-phenylisocyanate (MDI) and 4,4′-hexafluoroisopropylidene-bis-phthalic anhydride (6FDA). The polymers PTMO1000 (1 − x equiv.) + MDEA (x equiv.)/MDI (2 equiv.)/6FDA (1 equiv.) were obtained in high yields (>90%) through original synthesis, involving the reaction of macrodiisocyanates with an aromatic dianhydride in two steps only. A wide range of complementary techniques including two-dimensional NMR showed that the new method enabled a very good control of the polymer structure. In particular, the tertiary amine content of the PUI copolymers was easily varied over the whole composition range (x: 0 → 1), with interesting prospects for the design of a wide range of ion-containing poly(urethaneimides) by quaternising the tertiary amine groups. The PUI properties (e.g. solubility, viscosity, film-forming ability, etc.) clearly depended upon their tertiary amine content. Up to a tertiary amine content of x = 0.7 equiv., the very good film-forming character of the PUIs enabled to cast strong films suitable for permeability investigations.     

Analysis of pyrolysis products formed from ethylene-tetrafluoroethylene heterosequences of poly(ethylene-co-tetrafluoroethylene)

Poly(ethylene-co-tetrafluoroethylene) (PETFE) was pyrolyzed and the pyrolysis products formed from the ethylene-tetrafluoroethylene heterosequences were analyzed using gas chromatography/mass spectrometry (GC/MS). Major pyrolysis products were 3,3-difluoropropene (DFP), 3,3,4,4-tetrafluoro-1-butene (TFB), 1,1,2,2,3,3-hexafluorocyclopentane (HFCP), 1,1,2,2,3,3-hexafluorocyclohexane (HFCH), 1,1,2,2,3,3,4,4-octafluorocyclohexane (OFCH), and 3-trifluoromethyl-3,4,4,5,5-pentafluorocyclohexene (FMPFCH). Their formation mechanisms were proposed. Peak intensity ratios of HFCP, HFCH, and FMPFCH compared to OFCH increased as the pyrolysis temperature increased, while those of DFP, TFB, HFCP, and HFCH compared to tetrafluoroethylene decreased. Order of the relative abundances of the major pyrolysis products formed from PETFE was OFCH > HFCP > HFCH > TFB > DFP. The order may be due to the difference in bond energies of CH₂-CH₂, CF₂-CH₂, and CF₂-CF₂. Formation of the pyrolysis product through the CH₂-CH₂ bond cleavage was more favorable than those through the CF₂-CH₂ and CF₂-CF₂ ones.