Carbene adduct of cyclopalladated ferrocenylimine‐assisted synthesis of aminopyridine derivatives by the amination of chloropyridines with primary and secondary amines

An efficient, simple way to synthesize aminopyridine derivatives is presented, based on Buchwald–Hartwig aminations. Using 1 mol% N‐heterocyclic carbene adduct of cyclopalladated ferrocenylimine in the presence of 1.5 equiv. ^tBuOK as base in dioxane at 110°C offered moderate to excellent yields in the reaction of chloropyridines with primary and secondary amines, including sterically hindered amines and alkyl amines.     

Synthesis of homoallylic amines and acylhydrazides by tin powder‐promoted multicomponent one‐pot allylation reactions

An efficient process for the synthesis of homoallylic amines and N′‐homoallylic hydrazides is developed from the one‐pot reaction of carbonyl compounds, amines or N‐acylhydrazines, allyllic bromide and tin powder using water as solvent. N‐Acylhydrazines are found to be more reactive than amines in these processes. They can react not only with aldehydes but also with ketones to give the corresponding N′‐homoallylic hydrazides. Copyright © 2016 John Wiley & Sons, Ltd.     

Preparation of trimethylsilyl ethers of 3-azetidinols. Scope and Limitations

Preparation of the trimethylsilyl ethers of 1-alkyl-3-azetidinols from non-hindered primary amines and epichlorohydrin by conversion of the intermediate 1-(alkylamino)-3-chloro-2-propanols to their trimethylsilyl ethers by either N-(trimethylsilyl)acetamide or by 1-(trimethylsilyl)imidazole followed by ring closure in acetonitrile is described. This sequence of reactions fails for aromatic amines, but appears to be general for all primary aliphatic amines, although the condensation of hindered amines with epichlorohydrin occurs slowly. Several novel azetidinols, in which the N-alkyl substituent itself contains a second heterocyclic system, are reported. In addition, the pK_A's of several m. and p-substituted 1-benzylazetidinols correlates well with the Hammett equation.     

MgBr2 · OEt2: A Lewis Acid Catalyst for the O- and N-Boc Protection of Phenols and Amines

MgBr₂ · OEt₂ efficiently catalyzes the O- and N-tert-butoxycarbonylation of functionalized phenols and amines. The presented procedure is operationally simple and done under solvent-free conditions.     

Photogeneration of polyfunctional amines and novel thermal curing reactions of epoxy resin and polyurethane oligomer using these amines

Photochemical reactions of various blocked polyfunctional amines such as bis(4-formylaminophenyl)methane (FAPM), bis(4-acetylaminophenyl)methane (AAPM), bis(4-benzoylaminophenyl)methane (BAPM), 2,4-diformylaminotoluene (DFAT), m-xylene diformamide, and bis[[(2-nitrobenzyl)oxy]carbonyl]hexane-1.6-diamine were carried out to give the corresponding free amines in THF solution, in epoxy resin, or in polyurethane oligomer with terminal isocyanate groups. Photolysis of FAPM and DFAT to produce the corresponding polyfunctional amines such as 4,4'-methylenedianiline and 2,4-diaminotoluene proceeded with 80 and 75% conversions, respectively, in THF solution under UV irradiation at 5 h. AAPM and BAPM also produced the corresponding photo-Fries rearrangement products with 32 and 38% conversions, respectively, under the same irradiation conditions. The photolysis of those compounds also occurred with similar conversions in the epoxy resin and in the polyurethane oligomer under UV irradiation; and the thermal curing reactions of the epoxy resin and the polyurethane oligomer with photogenerated polyfunctional amines proceeded smoothly after heating at 140°C for 2 hrs. © 1993 John Wiley & Sons, Inc.     

Structure-Property Relationships in the Basicity and Lipophilicity of Arylalkylamine Oxides

Homologous N,N-dimethyl-phenylalkylamine oxides and N,N-dimethyl-diphenylalkylamine oxides were prepared. Their basicity and lipophilicity (octan-1-ol/H₂O) were compared to those of the parent amines. In contrast to the amines, the basicity of all N,N-dimethyl-arylalkylamine oxides showed very limited pK_a variations (range 4.65 – 5.01) with increasing chain length and number of Ph groups. The N-oxides in their neutral form had a log P^N value lower by 2.77±0.34 (n=9) units than that of the parent amine. The log P^C of the cationic N,N-dimethyl-diphenylalkylamines was lower than that of their neutral form, with a decrement diff(log P^N−C) that increased from 3.25 to 4.21 in the homologous series. Unexpectedly, the decrement diff(log P^N−C) for the N-oxides was much smaller than for the tertiary amines, being 0.23 for the aliphatic N,N-dimethyl-pentylamine oxide, 0.47±0.13 for the phenylalkylamine oxides, and 0.80±0.07 for the diphenylalkylamine oxides. In fact, the protonated N-oxides had log P^C values that were quite comparable to those of the protonated parent amines. Because of the differences in basicity, the difference in distribution coefficients at physiological pH (log D^7.4) between a tertiary arylalkylamine and its N-oxide was 0.82±0.66 (n=9). The pharmacokinetic implication is that N-oxygenation may have a smaller effect on the urinary excretion of tertiary amines than usually assumed.     

Non-Planar Structures of Sterically Overcrowded Trialkylamines

Several amines with three bulky alkyl groups at the nitrogen atom, which exceed the steric crowding of triisopropylamine significantly, were synthesized, mainly by treating N-chlorodialkylamines with Grignard reagents. In six cases, namely tert-butyldiisopropylamine, 1-adamantyl-tert-butylisopropylamine, di-1-adamantylamines with an additional N-cyclohexyl or N-exo-2-norbonyl substituent, as well as 2,2,6,6-tetramethylpiperidine derivatives with N-cyclohexyl or N-neopentyl groups, appropriate single crystals were generated that enabled X-ray diffraction studies and analysis of the molecular structures. The four noncyclic amines adopt triskele-like conformations, and the sum of the three C−N−C angles is always in the range of 351.1° to 352.4°. Consequently, these amines proved to be structurally significantly flatter than trialkylamines without steric congestion, which is also signalized by the smaller heights of the NC₃ pyramids (0.241–0.259 Å). There is no clear correlation between the heights of these pyramids and the degree of the steric crowding in the new amines, presumably because steric repulsion is partly compensated by dispersion interaction. In the cases of the two heterocyclic amines, the steric stress is smaller, and the molecular structures include quite different conformations. Quantum chemical calculations led to precise gas-phase structures of the sterically overcrowded trialkylamines exhibiting heights of the NC₃ pyramids and preferred molecular conformers which are similar to those resulting from the X-ray studies.     

Thiocarbamyolation of amine-containing compounds

Thiocarbamoylation of primary and secondary aliphatic amines with tetramethylthiuram disulfide in various solvents at different temperatures was studied. At 110°C, the reactions with primary amines afforded mixed,N,N-dimethyl-N′-alkyl(cycloalkyl)thioureas and symmetricalN,N′-dialkyl(cycloalkyl)thioureas as the final products, while the reactions with secondary amines gave mixtures of dithiocarbamate salts with “symmetrical” derivatives predominating.     

N,N ′-Diiodo-N,N′-1,2-ethanediylbis(p-toluenesulfonamide) as an Efficient Catalyst for Acetylation of Alcohols,Phenols, Amines,and Thiols Under Solvent-Free Conditions

N,N′-Diiodo-N,N′-1,2-ethanediylbis(p-toluenesulfonamide) (NIBTS) is a highly efficient catalyst for the acetylation of alcohols, phenols, amines, and thiols under solvent-free conditions. Primary, secondary, tertiary alcohols; phenols; amines; and thiols can be easily acetylated in good to excellent yields at 80 °C.     

Determination of aromatic amines in environmental water samples using solid-phase extraction modified with sodium dodecyl sulphate and micellar liquid chromatography

Extraction and determination of seven aromatic amines in environmental water samples were performed with solid-phase extraction (SPE) and micellar liquid chromatography (MLC) using experimental design. Extraction of aromatic amines was carried out with a C₁₈ cartridge modified with sodium dodecyl sulphate (SDS). The washing solution and elution solvent for extraction of aromatic amines were aqueous solution containing 5% (v/v) acetonitrile and 5% (v/v) acetone and 3 mL methanol, respectively. The chemometrics approach was applied for the separation optimisation of these compounds using MLC. Different mobile phase compositions were used for modelling based on retention times to obtain the best separation using central composite design. The optimum mobile phase composition for separation and determination of analytes in water samples was 69 mM SDS, 9% v/v 1-propanol and pH = 6.4. Recoveries were between 84.8–93.5% with relative standard deviation (RSD) less than 5.8% (n = 5). Limits of detection and linear range were 1–4.5 and 3.1–125.0 µg/L, respectively. The proposed method was applied to determine the aromatic amines in real samples (river and well waters). Amount of 4-nitroaniline and 3-nitroaniline in river water sample were 2.15 and 1.91 µg/L, respectively.     

Continuous‐Flow Oxidative Cyanation of Primary and Secondary Amines Using Singlet Oxygen

Primary and secondary amines can be rapidly and quantitatively oxidized to the corresponding imines by singlet oxygen. This reactive form of oxygen was produced using a variable‐temperature continuous‐flow LED‐photoreactor with a catalytic amount of tetraphenylporphyrin as the sensitizer. α‐Aminonitriles were obtained in good to excellent yields when trimethylsilyl cyanide served as an in situ imine trap. At 25°C, primary amines were found to undergo oxidative coupling prior to cyanide addition and yielded secondary α‐aminonitriles. Primary α‐aminonitriles were synthesized from the corresponding primary amines for the first time, by an oxidative Strecker reaction at –50 °C. This atom‐economic and protecting‐group‐free pathway provides a route to racemic amino acids, which was exemplified by the synthesis of tert‐leucine hydrochloride from neopentylamine.     

Structure and Synthesis of a New Library of N,N-Bis-[1,2,4]triazol-1-ylmethyl-amino Compounds

New N,N-bis(triazol-1-ylmethyl)amines have been prepared in one step by condensation of 1-(hydroxymethyl)triazole with a series of primary substituted aromatic amines. These reactions were carried out in refluxed CH₃CN for 4 h. The products were recuperated with excellent and good yields (75–90.5%). The x-ray crystallography structure of one of them has been studied.     

Trans ligand influence in cobalt(III) Schiff base complexes: Electronic and steric effects on the kinetics of hydrolysis

Rate constants for the hydrolysis (k_h) of six different amines in trans‐[Co((BA)₂en)(amine)₂]ClO₄ complexes (amine = aniline 1a , para‐toluidine 1b , benzylamine 1c (primary amines), pyrrolidine 2a , piperidine 2b , morpholine 2c (secondary amines), and (BA)₂en = Bisbenzoylacetoneethylenediiminato) in mixed methanol/water (1:1) solvent have been determined between 30 and 55°C. The hydrolysis product of 2c , trans‐[Co((BA)₂en)(morpholine)(H₂O)]ClO₄, has been separately prepared and characterized by UV–vis and ¹H NMR spectroscopy. Depending on the nature of the axial amine ligand the limiting first‐order rate constants for the amine hydrolysis at 40°C range from (3.42 ± 0.10) × 10^?5 to (5.32 ± 0.13) × 10^?5 s^?1. At the first glance, a reasonable trend cannot be established between k_h and the basicity or the inductive trans effect of the amine ligands. However, when the complexes are classified into two groups, based on the type of the amine (primary and secondary), the values of k_h correlate well with the basicity or inductive effect of the amine in each group. The observed trend in k_h values for the complexes with primary amines is 1a (5.32 ± 0.13) × 10^?5 s^?1 > 1b (3.51 ± 0.14) × 10^?5 > 1c (1.72 ± 0.03) × 10^?5 (40°C), which is opposite to the amine basicity strength. In the case of the complexes with secondary amines, the observed trend in k_h values is in accord with amine basicity (or inductive trans effect), i.e. 2a (5.02 ± 0.22) × 10^?5 > 2b (4.18 ± 0.10) × 10^?5 > 2c (3.42 ± 0.10) × 10^?5 s^?1 (40°C). © 2002 Wiley Periodicals, Inc. Int J Chem Kinet 34: 387–393, 2002     

Polyimides derived from bismethylolimides. II. Polyamine-imides from bismethylolimides and diamines

Compounds in the N-methylolimide group reacted smoothly with amines in the presence of water to yield the corresponding condensation products. Polycondensations of bismethylolimides, N,N′-bismethylolpyromellitic diimide, and N,N′-bismethylolbenzophenonetetracarboxylic diimide, with amines such as aromatic diamines, piperazine, and n-butylamine, were carried out in DMAc that contained 1% water to produce linear polyamine-imides. The polyamine-imides assumed various colors, from very pale yellow to deep purple, and had inherent viscosities in the 0.07–0.37-dl/g range. Most of these polymers were soluble in polar solvents such as DMAc and DMSO. The thermal stability of the polymers was examined by thermogravimetric analysis; decomposition started at 210–350°C and weight residue at 500°C was 22–85% in air.     

Direct conversion of secondary phosphine oxides and H‐phosphinates with [Di(acyloxy)iodo]benzenes to phosphinic and phosphonic amides

The reaction of [di(acyloxy)iodo]benzene with secondary phosphine oxides or H‐phosphinates in the presence of primary or secondary amines allows one to obtain phosphinic or phosphonic acids amides in the one‐pot process. We take advantage of the strong acylating system DAIB/R₂P(O)H to phosphinylation of amines. However, the reaction mechanism is multipathway and causes yields of phosphinic or phosphonic acids amides to be moderate. When the concentration of amines is low, the intermolecular process plays a main role leading to the formation of carboxylic amides through mixed phosphoric–carboxylic anhydride, and also in the low concentration of amines, tetrahydrofuran effectively competes with the amines in the nucleophilic attack on the acylating intermediates. © 2009 Wiley Periodicals, Inc. Heteroatom Chem 20:81–86, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20514     

Concerted aminolysis of diaryl carbonates: Kinetic sensitivity on the basicity of the nucleophile,nonleaving group,and nucleofuge

The kinetics of the reactions of 4‐methylphenyl, phenyl, and 4‐chlorophenyl 2,4,6‐trinitrophenyl carbonates ( 1 , 2 , and 3 , respectively) with a series of anilines and secondary alicyclic (SA) amines has been carried out spectrophotometrically in 44 wt% ethanol–water, at 25.0°C, ionic strength 0.2 M. The Brønsted plots (statistically corrected) for the reactions of carbonates 1 – 3 with anilines and SA amines were linear with slopes (β_N) in the range of 0.69–0.78 and 0.45–0.48, respectively, attributed to a concerted mechanism. The negative values found for the sensitivity of log k_N to the basicity of the nonleaving (β_nlg) and leaving (β_lg) groups are discussed. Anilines are more reactive than isobasic SA amines, probably because of the greater steric hindrance offered by the latter. © 2012 Wiley Periodicals, Inc. Int J Chem Kinet 44: 604–611, 2012     

Thiocarbamoylation of amine-containing compounds

Thiocarbamoylation of aliphatic amines with tetramethylthiuram disulfide (TMTD) was studied. The reactions were established to proceed according to a two-stage mechanism. In the first stage,S-(thiocarbamoyl)thiohydroxylamines and dimethyl dithiocarbamates are formed. The latter exist in equilibrium with dimethyldithiocarbamic acid, which can undergo decomposition to give dimethylamine and carbon disulfide. In the second stage, several competitive transformations of these intermediates into the final products occur,viz., (1) the reactions of CS₂ with primary amines on heating (70–110 °C) yield mixed and symmetrical thioureas and the reactions of CS₂ with secondary amines give symmetrical dithiocarbamates, and (2) insertion of CS₂ intoS-(thiocarbamoyl)thiohydroxylamines affords thiuram disulfides. Thiuram disulfides formed from primary amines decompose to give isothiocyanates, which are converted into thioureas by condensation with amines, whereas thiuram disulfides which are obtained in the reactions with secondary amines and which cannot form thioureas react with amines analogously to TMTD. For Part 4, see Ref. 1. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 334–342, February, 2000.     

Homo‐double helix formation of an optically active conjugated polymer bearing carboxy groups and amplification of the helicity upon complexation with achiral and chiral amines

An optically active, m‐terphenyl‐based π‐conjugated polymer bearing carboxy groups was synthesized by the copolymerization of the diethynyl monomer bearing a carboxy group with (S,S)‐2,5‐bis(2‐methylbutoxy)‐1,4‐dibromobenzene using Sonogashira reaction. The copolymer showed a weak circular dichroism (CD) in the main‐chain chromophore region due to a homo‐double helix formation with an excess helical handedness biased by the chiral alkoxy substituents through self‐association. However, upon complexation with achiral amines, such as piperidine, the CD intensity of the polymer significantly increased resulting in the formation of a greater excess one‐handed homo‐double helix via hydrogen‐bonded inclusion complexation with the achiral amines between each strand, leading to the amplification of the helicity. A preferred‐handed homo‐double helix was also induced in the polymer in the presence of nonracemic amines. The effect of the achiral and chiral amines on the homo‐double helix formation was investigated by comparing the CD spectra of the polymer to those of its model dimer. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 990–999     

Kinetics and mechanism of the amine exchange reactions of 2-aminopyridine derived Schiff-base ligands and their copper(II) complexes

The kinetics and product analyses of the amine exchange reactions of two 2-aminopyridine derived Schiff-base ligands and their monomeric bischelate and dimeric copper(II) complexes have been studied. The Schiff-base ligands investigated underwent amine exchange reactions with n-butyl, cyclohexyl, t-butyl amines. The coordination of the Schiff-base ligands to copper(II) rendered the amine exchange reactions slower. With n-butyl and cyclohexyl amines, parallel first- and second-order terms on their concentrations are observed for the amine exchange reactions of copper(II) bischelates and dimer. The kinetic data favor a mechanism involving a rate-limiting elimination of 2-aminopyridine from a diaminoacetal intermediate in preference to a scheme in which a dissociation of the complexes into free ligands and Cu(II) may precede the amine exchange. The steric factors influence the amine exchange reactions of Cu(II) bischelates with the bulkier amines reacting slower as given by the order t-butylamine (3.3 ± 0.3 × 10^?3 dm³/mol·s) < cyclohexylamine (0.2 ± 0.03 dm³/mol·s) < n-butylamine (2.2 ± 0.2 dm³/mol·s). The bulkiness of the t-butyl group and the constraints imposed by the changes in the coordination geometry of Cu(II) on amine exchange not only render the reactions of Cu(II) bischelates slower but also make the formation of the mixed adduct ([N-(5-methyl)-2-pyridyl salicylaldimine][N-t-butyl salicylaldimine] Cu(II)) more favored.     

Cobalt‐Catalyzed Electrophilic Amination of Aryl‐ and Heteroarylzinc Pivalates with N‐Hydroxylamine Benzoates

Aryl‐ and heteroarylzinc pivalates can be aminated with O‐benzoylhydroxylamines at 25 °C within 2–4 h in the presence of 2.5–5.0 % CoCl₂?2 LiCl to furnish the corresponding tertiary arylated or heteroarylated amines in good yields. This electrophilic amination also provides access to diarylamines and aryl(heteroaryl)amines. A new tuberculosis drug candidate (Q203) was prepared in six steps and 56 % overall yield by using this cobalt‐catalyzed amination as the key step.