Primary Amide Group Research Articles

Ammonolysis of morpholine‐2,5‐diones: participation of the primary amide group. Part 2

The ammonolysis of three morpholine‐2,5‐dione derivatives was investigated and the mechanism ascertained by kinetic studies and theoretical calculations. The kinetics, followed by high‐performance liquid chromatography analysis, evidenced the presence of two intermediates, which were isolated and characterized. The ammonolysis occurs with a complex mechanism involving two consecutive reactions followed by two parallel ones. The second step of the whole reaction involves an anchimeric assistance of the primary amide group. The pseudo‐first‐order rate constants were calculated by appropriate equations, which describe the single steps of the process. Computational density functional theory investigations of vicinal primary amide group participation were performed using a model compound, and the transition states were generated. The theoretical calculations evidenced the essential role exerted by ammonia, which acts as a proton transfer. Copyright © 2011 John Wiley & Sons, Ltd.

Hydrosiloxane–Ti(OiPr)4: an efficient system for the reduction of primary amides into primary amines as their hydrochloride salts

A simple and useful method for the reduction of primary amides into the corresponding amines using a polymethylhydrosiloxane (PMHS)–Ti(OiPr)4 reducing system is described. Aromatic as well as aliphatic primary amides are reduced in high selectivity and excellent yields. The reduction could proceed via dehydration of the primary amide group into the corresponding nitrile which is then reduced into the corresponding primary amine.

SARs at the Monoamine Transporters for a Novel Series of Modafinil Analogues

A series of modafinil (1) analogues was synthesized wherein 1) para-halo-substitutents were added to the aryl rings, 2) the sulfoxide function was removed, and 3) the primary amide group was replaced with secondary and tertiary amides and amines to investigate the effects of these chemical modifications on DAT, SERT and NET binding. In addition, the locomotor-stimulant effects in mice of (±)-modafinil (1), its R- and S-enantiomers and its para-chloro sulfinylacetamide analogue (5c) were compared to those of cocaine.

Complexes derived from the copper(II)/succinamic acid/ N, N′, N″-chelate tertiary reaction systems: Synthesis, structural and spectroscopic studies

The use of succinamic acid (H 2sucm) in Cu II/ N, N′, N″-donor [2,2′:6′,2″-terpyridine (terpy), 2,6-bis(3,5-dimethylpyrazol-1-yl)pyridine (dmbppy)] reaction mixtures yielded compounds [Cu(Hsucm)(terpy)] n (ClO 4) n ( 1), [Cu(Hsucm)(terpy)(MeOH)](ClO 4) ( 2), [Cu 2(Hsucm) 2(terpy) 2](ClO 4) 2 ( 3), [Cu(ClO 4) 2(terpy)(MeOH)] ( 4), [Cu(Hsucm)(dmbppy)] n (NO 3) n ·3 nH 2O ( 5 . 3 nH 2O), and [CuCl 2(dmbppy)]·H 2O ( 6·H 2O). The succinamate(−1) ligand exists in four different coordination modes in the structures of 1– 3 and 5, i.e., the μ 2-κ O:κ O′:κ O″ in 1 and 5 which involves asymmetric chelating coordination of the carboxylato group and ligation of the amide O-atom leading to 1D coordination polymers, the μ 2-κ 2 O:κ O′ in 3 which involves asymmetric chelating and bridging coordination of the carboxylato group, and the asymmetric chelating mode in 2. The primary amide group, either coordinated in 1 and 5, or uncoordinated in 2 and 3, participate in hydrogen bonding interactions, leading to interesting crystal structures. Characteristic IR bands of the complexes are discussed in terms of the known structures and the coordination modes of the Hsucm − ligands. The thermal decomposition of complex 5·3 nH 2O was monitored by TG/DTG and DTA measurements.

Synthetic, structural and spectroscopic studies of copper(II) complexes derived from the combination of the succinamate(−1) ligand with aromatic N,N′-chelates

The use of succinamic acid (H 2sucm)/N,N′-chelate (2,2′-bipyridine, bpy; 4,4′-dimethyl-2,2′-bipyridine, dmbpy; 1,10-phenanthroline, phen) ‘ligand blends’ in CuX 2· yH 2O (X = NO 3, y = 3; X = Cl, y = 0) chemistry has yielded the new complexes [Cu 2(Hsucm) 3(bpy) 2](NO 3)·0.5MeOH ( 1·0.5MeOH), [Cu 2(Hsucm)(OH)Cl(bpy) 2](OH)·3.6H 2O ( 5·3.6H 2O) and [Cu 2(Hsucm) 2Cl 2(phen) 2] ( 6). The succinamate(−1) ion behaves as a carboxylate ligand and exists in two different coordination modes in the structures of the above complexes, i.e., the common syn, syn μ 2-κ O:κ O′ in 1, 5 and 6, and the μ 2-κ 2 O:κ O′ in 1. The primary amide group of Hsucm − remains uncoordinated and participates in intermolecular hydrogen bonding interactions leading to 1D, 2D and 3D networks. Characteristic IR bands of the complexes are discussed in terms of the known structures and the coordination modes of the Hsucm − ligands.

Maleamate(–1) and Maleate(–2) Copper(II)–2,2′‐Bipyridine Complexes: Synthesis, Reactivity and Structural and Physical Studies

AbstractA systematic investigation of the 1:2:1:2 Cu(NO3)·2.5H2O/H2L/bpy/LiOH·H2O (H2L = maleamic acid) reaction system in MeCN/H2O was carried out. The compounds [Cu2(HL)2(bpy)2(H2O)2](NO3)2 (1), [Cu2(HL)2(bpy)2(H2O)2](NO3)2·2H2O (1·2H2O), [Cu2Li2(L′)2(bpy)2(H2O)6][Cu2(HL)2(bpy)2(H2O)2](NO3)4 (2), [Cu4(L′)2(NO3)2(bpy)4(H2O)2](NO3)2·2H2O (3·2H2O) and [Cu(L′)(bpy)]n·2nH2O (4·2nH2O) were isolated, depending on the crystallization method employed. Complexes 2, 3·2H2O and 4·2nH2O contain the maleate(–2) anion (L′2–), which was formed in situ through metal‐ion‐assisted hydrolysis of the primary amide group of H2L. Efforts to prepare complex 3 from the direct use of maleic acid (H2L′) afforded compounds 4·2nH2O, [Cu4(L′)2(NO3)2(bpy)4(H2O)2](NO3)2·2[Li(NO3)(H2O)3]·4H2O (5·4H2O) and [Cu(NO3)(bpy)(H2O)3](NO3) (6) from the 1:1:1:2 Cu(NO3)·2.5H2O/H2L′/bpy/LiOH·H2O reaction system in MeCN/H2O. The maleamate(–1) ligand presents the less common η1:μ2 coordination mode in the cations of 1, 1·2H2O and 2. The maleate(–2) ligand exhibits the η1:η1:η1:η1:μ3 coordination mode in the [CuII4] cations of 3·2H2O and 5·4H2O and in the [CuII2LiI2] heterometallic cation of 2. The crystal structures of the complexes are stabilized by various H‐bonding patterns. Characteristic IR bands of the complexes are discussed in terms of the known structures and the coordination modes of the ligands. Magnetic susceptibility measurements for 3·2H2O reveal weak ferromagnetic interactions along the periphery of the Cu4 rhombus (J = 3.3 cm–1, –2JijSiSj Hamiltonian formalism), which stabilizes an S = 2 ground state. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Delta agonist hydroxy bioisosteres: The discovery of 3-((1-benzylpiperidin-4-yl){4-[(diethylamino)carbonyl]phenyl}amino)benzamide with improved delta agonist activity and in vitro metabolic stability

We have investigated phenol replacements in a series of diaryl amino piperidine delta opioid agonists. From this study we have demonstrated that the hydroxy functional group can be replaced with a primary amide group, giving enhanced activity at the delta receptor, increased selectivity versus mu and kappa as well as improved in vitro metabolic stability.

Robust Organogels from Nitrogen-Containing Derivatives of (R)-12-Hydroxystearic Acid as Gelators: Comparisons with Gels from Stearic Acid Derivatives†

Thirteen members of a new class of low molecular-mass organogelators (LMOGs), amides, and amines based on (R)-12-hydroxystearic acid (HSA; i.e., (R)-12-hydroxyoctadecanoic acid) and the properties of their gels have been investigated by a variety of structural and thermal techniques. The abilities of these LMOGs, molecules with primary and secondary amide and amine groups and the ammonium carbamate salt of 1-aminooctadecan-12-ol, to gelate a wide range of organic liquids have been ascertained. Their gelating efficiencies are compared with those of HSA and the corresponding nitrogen-containing molecules derived from stearic acid (i.e., HSA that lacks a 12-hydroxyl group). Several of the HSA-derived molecules are exceedingly efficient LMOGs, with much less than 1 wt % being necessary to gelate several organic liquids at room temperature. Generally, the self-assembled fibrillar networks of the gels consist of spherulitic objects whose dimensions depend on the protocol employed to cool the precursor sol phases. X-ray studies indicate that the LMOG molecules are packed in lamellae within the fibers that constitute the spherulites. In addition, some of the organogels exhibit unusual thixotropic properties: they recover a large part of their viscoelasticity within seconds of being destroyed by excessive strain shearing. This recovery is at least an order of magnitude faster than for any other organogel with a crystalline fibrillar network reported to date. Correlations of these LMOG structures (as well as with those that lack a hydroxyl group along the n-alkyl chain, a headgroup at its end, or both) with the properties of their gels, coupled with the unusual theological properties of these systems, point to new directions for designing LMOGs and organogels.

Complexes derived from the copper(II) perchlorate/maleamic acid/2,2′-bipyridine and copper(II) perchlorate/maleic acid/2,2′-bipyridine reaction systems: Synthetic, reactivity, structural and spectroscopic studies

A systematic investigation of the reactions of Cu(ClO 4) 2 · 6H 2O with maleamic acid (H 2L) in the presence of 2,2′-bipyridine (bpy) has been carried out. The chemical and structural identity of the products depends on the solvent, the absence or presence of external hydroxides in the reaction mixture and the molar ratio of the reactants. Various reaction schemes have led to the isolation of the complexes [Cu 2(HL) 2(bpy) 2(H 2O) 2](ClO 4) 2 ( 1), [Cu 2(HL) 2(bpy) 2(H 2O) 2](ClO 4) 2 · 2H 2O ( 1 · 2H 2O), [Cu(L′′)(bpy)] n · 2 nH 2O ( 2 · 2 nH 2O), [Cu 2(L′′)(bpy) 2(H 2O) 2] n (ClO 4) 2 n · 0.5 nH 2O ( 3 · 0.5 nH 2O), [Cu 2(L′′) 2(bpy) 2] · 2MeOH ( 5 · 2MeOH), [Cu 2(L′) 2(bpy) 2(ClO 4) 2] ( 6) and [Cu(ClO 4) 2(bpy)(MeCN) 2] ( 7b), where L′′ 2− and L′ − are the maleate(−2) and monomethyl maleate(−1) ligands, respectively. The HL − ion has been transformed to L′′ 2− and L′ − in the known compounds 2 · 2 nH 2O and 6, respectively, via metal ion-assisted processes involving hydrolysis ( 2 · 2 nH 2O) and methanolysis ( 6) of the primary amide group. The reaction that leads to 6 takes place through the formation of the mononuclear complex [Cu(ClO 4) 2(bpy)(MeOH) 2] ( 7a), whose structure was assigned on the basis of its spectral similarity with the structurally characterized complex 7b. The structures of the cations in 1 and 1 · 2H 2O consists of two Cu II atoms bridged by the carboxylate groups of the two HL − ligands, each exhibiting the less common η 2 coordination mode; a chelating bpy molecule and a H 2O ligand complete square pyramidal coordination at each metal centre. The structure of the dinuclear repeating unit in the 1D coordination polymer 3 · 0.5 nH 2O consists of two Cu II atoms bridged by two syn,syn η 1: η 1: μ 2 carboxylate groups belonging to two L′′ 2− ions; each ligand bridged two neighboring [Cu II,II 2] units thus promoting the formation of a helical chain. The structure of the dinuclear molecule of complex 5 · 2MeOH consists of two Cu II atoms bridged by two η 2 carboxylate groups from two L′′ 2− ligands; the second carboxylate group of each maleate(−2) ligand is monodentately coordinated to Cu II, creating a remarkable seven-membered chelating ring. The L′ − ion behaves as a carboxylate-type ligand in 6, with the carboxylate group being in the familiar syn,syn η 1: η 1: μ 2 coordination mode; a chelating bpy molecule and a coordinated ClO 4 − complete five-coordination at each Cu II centre. The crystal structures of the complexes are stabilized by various H-bonding patterns. Characteristic IR bands of the complexes are discussed in terms of the known structures and the coordination modes of the ligands.

Influence of the substituent on amide nitrogen atom of N-acetyl tyrosine on interactions with β-cyclodextrin

The influence of substituent on amide nitrogen atom on the interactions of N-acetyl tyrosine amides with β-cyclodextrin was studied by means of steady-state and time-resolved fluorescence spectroscopy, 2D 1H NMR, and microcalorimetry. In comparison with AcTyr-OH a primary amide group only in a small degree modified the binding constant with β-CD, regardless of the structure (linear or branched) and the length of n-alkyl substituent which for primary amides (methyl, ethyl, n-propyl, iso-propyl, n-butyl, and sec-butyl), as determined from the microcalorimetric titrations, is in the range from 122 M −1 to 190 M −1, except for t-butyl substituent for which the highest binding constant (over 500 M −1) was determined. Moreover, for a branched substituent binding constants are a little higher in comparison with n-alkyl ones. For secondary amides (di-methyl, di-ethyl, di- n-propyl, di- iso-propyl, and di- iso-butyl) the binding constants are higher (in the range from 270 M −1 to 410 M −1).

Amide, Amino, Hydroxy and Aminopyridine Groups as Building Blocks for Carbohydrate Receptors

AbstractReceptors 1–3, incorporating primary amide, hydroxy or amino groups as recognition units used in nature, as well as 2‐aminopyridine units as heterocyclic analogues of the asparagine/glutamine primary amide side chains, were prepared and their binding properties towards neutral sugar molecules were studied. The design of these receptors was inspired by the binding motifs observed in the crystal structures of protein–carbohydrate complexes. The binding studies with β‐glucopyranoside 5 indicated the formation of complexes with 1:1 and 2:1 receptor–monosaccharide binding stoichiometries, with an overall β21 binding constant of 107–108 M–2. Both hydrogen bonding and interactions of the sugar CH groups with the central phenyl rings of the receptors contribute to the stabilisation of the receptor–sugar complexes. The syntheses, molecular modeling studies and binding properties of the receptors 1–3 are described, as well as comparative binding studies with receptor 4, lacking the third recognition site. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

A nonoxidic sol–gel route to titanium nitride and carbonitride films by primary aminecondensation

A solution phase route to films of nanocrystalline titanium nitride and carbonitride is reported. Transamination of Ti(NMe2)4 with primary amines results in primary amide groups which can self condense forming alkylimide bridges. The use of controlled amounts of amine results in sols in tetrahydrofuran; these can be coated onto silica substrates via a dip coating method. Pyrolysis of these films under ammonia or nitrogen leads to TiN and Ti(C,N) respectively.

Efficient Stereoselective Synthesis of γ‐N‐Glycosyl Asparagines by N‐Glycosylation of Primary Amide Groups.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis, characterization and thermal properties of soluble aromatic poly(amide imide)s

Novel diamines such as N, N′-bis(aminoaryl)terephthalamido-2-carboxylic acids (BATCA), which contain primary amine, amide and carboxylic acid groups and are soluble in dilute aqueous NaOH solution, were synthesized by reacting aromatic diamines with trimellitic anhydride chloride in dimethylformamide. Poly(amide imide)s containing 3:1 ratio of amide:imide groups in the polymer chain were prepared by low temperature solution polymerization of BATCAs with isophthaloyl chloride or terephthaloyl chloride in dimethylformamide at 5–10 °C to form poly(amide amic acid)s, and followed by treating with a mixture of triethylamine and acetic anhydride. The PAIs were soluble in polar aprotic solvents like dimethylformamide, dimethylacetamide, dimethylsulphoxide and N-methylpyrrolidone, and have inherent viscosities in the range of 0.30–0.66 dL/g. The PAIs were characterized by IR, 1H NMR and 13C NMR techniques. Thermogravimetric analysis (TGA) has shown that the initial decomposition temperatures of the polymers are in the range of 250–440 °C, depending upon the structures of diamine and diacid chloride. The glass transition temperatures of the PAIs are in the range of 128–320 °C. The IDT and T g values of the polymers containing terephthaloyl unit are higher by about 20–40 °C than those of the polymers with isophthaloyl unit. BATCA could be utilized for the preparation of thin film composite membranes having PAA/PAI barrier layer on PES by in situ interfacial polymerization with IPC/TPC/TMC.

Efficient Stereoselective Synthesis of γ-N-Glycosyl Asparagines by N-Glycosylation of Primary Amide Groups

The efficient and elegant synthesis of N-glycosides by N-glycosylation of asparagine-containing peptides is described. Glycosylation of primary amides with glycosyl N-phenyltrifluoroimidates in the presence of a catalytic amount of TMSOTf in nitromethane smoothly proceeded to provide the corresponding N-glycosyl amino acids in excellent yields. This coupling method was adaptable to the coupling of various glycosyl donors with amino acids and peptides.

Coefficient of friction reduction of ethylene-co-acrylic acid film: Effects of grafted 12-aminododecanamide and solvent exposure

The effect of covalently bound 12-aminododecanamide on the surface coefficient of friction (COF) of ethylene–acrylic acid copolymer (EAA) films was investigated. The reaction involved grafting 12-aminododecanoic acid to the inherent carboxylic acid groups on the film, followed by amidation of the grafted amino acid. Conversion of film carboxylic acid groups to primary amide groups was also conducted to compare the impact of direct surface amidation. Subsequent measurements showed that both surface amidation schemes reduced the kinetic COF from 0.30 to 0.15 ∼ 0.18. Repetitive COF testing revealed that amide-modified EAA films maintained low COF values that were independent of the number of COF test runs. However, control experiments showed that COF values also depended greatly on simply exposing film to the various reaction solvents, which increased surface roughness. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 97: 2242–2248, 2005

Synthesis of 4-Aza Analogs of Epothilone D

An efficient synthesis of epothilone D analogs of type 1 has been developed, which is based on a highly diastereoselective Evans aldol reaction as one of the key steps. A profound difference in the relative stabilities ofTBS-protecting groups on C7-O and C15-O was observed between secondary and primary amide groups at C5-N4. Although modeling studies had suggested analogs of type 1 to assume a conformation similar to the NMR-derived conformation of tubulin-bound epothilone As compounds la-d were found to be significantly less active than the parent compound epothilone D.

C.I. Pigment Red 266.

AbstractFor Abstract see ChemInform Abstract in Full Text.

C.I. Pigment red 266.

C.I. Pigment Red 266, or 4-[[4-(aminocarbonyl)phenyl]hydrazono]-N-(2-methoxyphenyl)-3-oxo-3,4-dihydronaphthalene-2-carboxamide, C(25)H(20)N(4)O(4), adopts the keto-hydrazone tautomeric form with significant intramolecular hydrogen bonding. The molecules pack to form layers involving an extensive network of intermolecular hydrogen bonds, in which the primary amide group plays a prominent role. The good technical performance of this pigment in application may be attributed principally to the pattern of intra- and intermolecular hydrogen bonding.

Solvent-induced polymorphism of three-dimensional hydrogen-bonded networks of hexakis(4-carbamoylphenyl)benzene.

The crystal structures for three types of three-dimensional (3-D) hydrogen-bonded networks of hexakis(4-carbamoylphenyl)benzene (1), the network morphologies of which depend greatly on crystallization conditions, have been determined. When this compound is crystallized from hot DMSO, the resulting crystals, 1.12DMSO (orthorhombic, Pca2(1)), showed a 3-D hydrogen-bonded porous network (type A) via 1-D catemer chains as a hydrogen-bonding motif of six primary amide groups. The type A network creates chambers surrounded by six molecules of 1 and channels along the c axis to give the highest porosity among the network polymorphs of 1 investigated here. Crystallization from a boiling mixture of n-PrOH and water gave 1.6n-PrOH (monoclinic, P2(1)/c), which exhibits another type of 3-D hydrogen-bonded porous network (type B) via cyclic dimers as another hydrogen-bonding motif of six primary amide groups. The type B network leads to triangle-like channels along the a axis having a cross section of ca. 9.2 x 9.7 x 9.7 A (including van der Waals radii). The crystal structure of 1.H(2)O (monoclinic, P2(1)/c), which was produced under hydrothermal conditions, showed a nonporous 3-D hydrogen-bonded network chain of amide groups (type C) composed of a mixed hydrogen bonding motif of helical catemer chains/cyclic dimer/catemer. Solvent-induced topological isomerism of these 3-D hydrogen-bonded networks of 1 arises from (i) the guest inclusion ability based on a radially functionalized hexagonal structure of 1, (ii) the correlation between the hydrogen bond donor ability of the syn and anti protons of the primary amide group in host 1 and the hydrogen bond acceptor ability of the oxygen atoms of 1 and guest solvents, and (iii) the polarity of the bulk crystallization solvents.