N‐Chloro­acetyl‐β‐alanine

The β‐alanine residue of the title compound, C₅H₈ClNO₃, has a ggt folded conformation, which is mainly stabilized through intermolecular N—H⋯O=C (amide–acid) and O—H⋯O=C (acid–amide) hydrogen bonds. In addition, a cis conformation is found for the Cl—CH₂—C(=O)—NH torsion angle, which is associated with the presence of an intramolecular hydrogen bond.     

(S,S)‐4′′‐Cyano‐7,7′′‐dimethoxy‐3′,6′‐dioxodispiro[indane‐2,2′‐piperazine‐5′,2′′‐indane]‐4‐carboxamide methanol solvate: interrupting the amide‐to‐amide hydrogen‐bonded tape

The title methanol solvate, C₂₄H₂₂N₄O₅·CH₃OH, forms an extended three‐dimensional hydrogen‐bonded structure, assisted by the presence of several good donor and acceptor sites. It shows none of the crystal packing features typically expected of piperazinediones, such as amide‐to‐amide R₂²(8) hydrogen bonding. In this structure the methanol solvent appears to play only a space‐filling role; it is not involved in any hydrogen bonding and instead is disordered over several sites. This study reports, to the best of our knowledge, the first crystal structure of an indane‐containing piperazinedione compound which exhibits a three‐dimensional hydrogen‐bonded structure formed by classical (N—H...O and N—H...N) hydrogen‐bonding interactions.     

Three‐dimensional hydrogen‐bonded structures in the hydrated proton‐transfer salts of isonipecotamide with the dicarboxylic oxalic and adipic acid homologues

The structures of the 1:1 hydrated proton‐transfer compounds of isonipecotamide (piperidine‐4‐carboxamide) with oxalic acid, 4‐carbamoylpiperidinium hydrogen oxalate dihydrate, C₆H₁₃N₂O⁺·C₂HO₄⁻·2H₂O, (I), and with adipic acid, bis(4‐carbamoylpiperidinium) adipate dihydrate, 2C₆H₁₃N₂O⁺·C₆H₈O₄²⁻·2H₂O, (II), are three‐dimensional hydrogen‐bonded constructs involving several different types of enlarged water‐bridged cyclic associations. In the structure of (I), the oxalate monoanions give head‐to‐tail carboxylic acid O—H...O_carboxyl hydrogen‐bonding interactions, forming C(5) chain substructures which extend along a. The isonipecotamide cations also give parallel chain substructures through amide N—H...O hydrogen bonds, the chains being linked across b and down c by alternating water bridges involving both carboxyl and amide O‐atom acceptors and amide and piperidinium N—H...O_carboxyl hydrogen bonds, generating cyclic R₄³(10) and R₃²(11) motifs. In the structure of (II), the asymmetric unit comprises a piperidinium cation, half an adipate dianion, which lies across a crystallographic inversion centre, and a solvent water molecule. In the crystal structure, the two inversion‐related cations are interlinked through the two water molecules, which act as acceptors in dual amide N—H...O_water hydrogen bonds, to give a cyclic R₄²(8) association which is conjoined with an R₄⁴(12) motif. Further N—H...O_water, water O—H...O_amide and piperidinium N—H...O_carboxyl hydrogen bonds give the overall three‐dimensional structure. The structures reported here further demonstrate the utility of the isonipecotamide cation as a synthon for the generation of stable hydrogen‐bonded structures. The presence of solvent water molecules in these structures is largely responsible for the non‐occurrence of the common hydrogen‐bonded amide–amide dimer, promoting instead various expanded cyclic hydrogen‐bonding motifs.     

Synthesis,antitumor activity and crystal structure of the triphenyltin derivative of exo‐7‐oxa‐bicyclo[2,2,1]hept‐5‐ene‐3‐N‐p‐tolylamide‐2‐acid

The synthesis and crystal structure of­Ph₃SnO₂CCHCHCH:CHCH(O)CHCONHC₆H₄­CH₃·CH₂Cl₂ are reported. The monomer units­are bridged by the carbonyl oxygen of the amide group, thus forming a polymer in which each tin atom is best described as having a distorted five‐coordinate geometry. There is a relatively strong intramolecular hydrogen bond between the amide hydrogen and the ether oxygen. The in vitro antitumor activities of the title compound against HL‐60, BGC‐823, Bel‐7402, SKOV3, KB and Hela tumor lines are reported. The title compound shows a distinct advantage when the metal (tin) is introduced into the acid.Copyright © 2001 John Wiley & Sons, Ltd.     

Cyclic imides and an open‐chain amide carboxylic acid from the facile reaction of cis‐cyclohexane‐1,2‐carboxylic anhydride with the isomeric monofluoroanilines

The structures of the cyclic imides cis‐2‐(2‐fluorophenyl)‐3a,4,5,6,7,7a‐hexahydroisoindole‐1,3‐dione, C₁₄H₁₄FNO₂, (I), and cis‐2‐(4‐fluorophenyl)‐3a,4,5,6,7,7a‐hexahydroisoindoline‐1,3‐dione, C₁₄H₁₄FNO₂, (III), and the open‐chain amide acid rac‐cis‐2‐[(3‐fluorophenyl)carbamoyl]cyclohexane‐1‐carboxylic acid, C₁₄H₁₆FNO₃, (II), are reported. Cyclic imides (I) and (III) are conformationally similar, with comparable ring rotations about the imide N—C_ar bond [the dihedral angles between the benzene ring and the five‐membered isoindole ring are 55.40 (8)° for (I) and 51.83 (7)° for (III)]. There are no formal intermolecular hydrogen bonds involved in the crystal packing of either (I) or (III). With the acid (II), in which the meta‐related F‐atom substituent is rotationally disordered (0.784:0.216), the amide group lies slightly out of the benzene plane [the interplanar dihedral angle is 39.7 (1)°]. Intermolecular amide–carboxyl N—H...O hydrogen‐bonding interactions between centrosymmetrically related molecules form stacks extending down b, and these are linked across c by carboxyl–amide O—H...O hydrogen bonds, giving two‐dimensional layered structures which lie in the (011) plane. The structures reported here represent examples of compounds analogous to the phthalimides or phthalanilic acids and have little precedence in the crystallographic literature.     

Amide hydrogen bonding: control of the molecular and extended structures of two symmetrical pyridine‐2‐carboxamide derivatives

The crystal structures of two symmetrical pyridine‐2‐carboxamides, namely N,N′‐(propane‐1,3‐diyl)bis(pyridine‐2‐carboxamide), C₁₅H₁₆N₄O₂, (I), and N,N′‐(butane‐1,4‐diyl)bis(pyridine‐2‐carboxamide), C₁₆H₁₈N₄O₂, (II), exhibit extended hydrogen‐bonded sequences involving their amide groups. In (I), conventional bifurcated amide–carbonyl (N—H)...O hydrogen bonding favours the formation of one‐dimensional chains, the axes of which run parallel to [001]. Unconventional bifurcated pyridine–carbonyl C—H...O hydrogen bonding links adjacent one‐dimensional chains to form a `porous' three‐dimensional lattice with interconnected, yet unfilled, voids of 60.6 (2) ų which combine into channels that run parallel to, and include, [001]. 4% of the unit‐cell volume of (I) is vacant. Compound (II) adopts a Z‐shaped conformation with inversion symmetry, and exhibits an extended structure comprising one‐dimensional hydrogen‐bonded chains along [100] in which individual molecules are linked by complementary pairs of amide N—H...O hydrogen bonds. These hydrogen‐bonded chains interlock viaπ–π interactions between pyridine rings of neighbouring molecules to form sheets parallel with (010); each sheet is one Z‐shaped molecule thick and separated from the next sheet by the b‐axis dimension [7.2734 (4) Å].     

Glycosidic linkage,N‐acetyl side‐chain,and other structural properties of methyl 2‐acetamido‐2‐deoxy‐β‐d‐glucopyranosyl‐(1→4)‐β‐d‐mannopyranoside monohydrate and related compounds

The crystal structure of methyl 2‐acetamido‐2‐deoxy‐β‐d ‐glycopyranosyl‐(1→4)‐β‐d ‐mannopyranoside monohydrate, C₁₅H₂₇NO₁₁·H₂O, was determined and its structural properties compared to those in a set of mono‐ and disaccharides bearing N‐acetyl side‐chains in βGlcNAc aldohexopyranosyl rings. Valence bond angles and torsion angles in these side chains are relatively uniform, but C—N (amide) and C—O (carbonyl) bond lengths depend on the state of hydrogen bonding to the carbonyl O atom and N—H hydrogen. Relative to N‐acetyl side chains devoid of hydrogen bonding, those in which the carbonyl O atom serves as a hydrogen‐bond acceptor display elongated C—O and shortened C—N bonds. This behavior is reproduced by density functional theory (DFT) calculations, indicating that the relative contributions of amide resonance forms to experimental C—N and C—O bond lengths depend on the solvation state, leading to expectations that activation barriers to amide cis–trans isomerization will depend on the polarity of the environment. DFT calculations also revealed useful predictive information on the dependencies of inter‐residue hydrogen bonding and some bond angles in or proximal to β‐(1→4) O‐glycosidic linkages on linkage torsion angles ? and ψ. Hypersurfaces correlating ? and ψ with the linkage C—O—C bond angle and total energy are sufficiently similar to render the former a proxy of the latter.     

Tris­[2‐(benzoyl­amino)­ethyl]­amine

Tris­[2‐(benzoyl­amino)­ethyl]­amine [alternatively, N,N′,N′′‐(nitrilo­tri­ethyl)­tri­benz­amide], C₂₇H₃₀N₄O₃, adopts a folded structure, forming a symmetrical cavity with an average depth of 7.3 Å and width ranging from 4.1–4.4 Å. The folded structure is a result of one intramolecular N—H?O hydrogen bond. A linear chain motif along the c axis best describes the extended intermolecular N—H?O hydrogen bonding.     

Hydro­gen bonding in N,N′‐bis­[(1S)‐2‐azido‐1‐(2‐methyl­propyl)­ethyl]­oxal­amide: twofold symmetry of R(10) hydrogen‐bonded dimers connected into an α‐network

The title compound, C₁₄H₂₆N₈O₂, belongs to a class of retropeptides with an oxal­amide unit (–NH–CO–CO–NH–), and is a precursor for the synthesis of an amine‐terminal gelator. The compound is a good synthon for one‐dimensional hydrogen bonding. The crystal structure reveals a hydrogen‐bonded cyclic dimer with unusual twofold rotation symmetry.     

Hydrogen bonding in cyclic imides and amide carboxylic acid derivatives from the facile reaction of cis‐cyclohexane‐1,2‐carboxylic anhydride with o‐ and p‐anisidine and m‐ and p‐aminobenzoic acids

The structures of the open‐chain amide carboxylic acid rac‐cis‐2‐[(2‐methoxyphenyl)carbamoyl]cyclohexane‐1‐carboxylic acid, C₁₅H₁₉NO₄, (I), and the cyclic imides rac‐cis‐2‐(4‐methoxyphenyl)‐3a,4,5,6,7,7a‐hexahydroisoindole‐1,3‐dione, C₁₅H₁₇NO₃, (II), chiral cis‐3‐(1,3‐dioxo‐3a,4,5,6,7,7a‐hexahydroisoindol‐2‐yl)benzoic acid, C₁₅H₁₅NO₄, (III), and rac‐cis‐4‐(1,3‐dioxo‐3a,4,5,6,7,7a‐hexahydroisoindol‐2‐yl)benzoic acid monohydrate, C₁₅H₁₅NO₄·H₂O, (IV), are reported. In the amide acid (I), the phenylcarbamoyl group is essentially planar [maximum deviation from the least‐squares plane = 0.060 (1) Å for the amide O atom] and the molecules form discrete centrosymmetric dimers through intermolecular cyclic carboxy–carboxy O—H...O hydrogen‐bonding interactions [graph‐set notation R₂²(8)]. The cyclic imides (II)–(IV) are conformationally similar, with comparable benzene ring rotations about the imide N—C_ar bond [dihedral angles between the benzene and isoindole rings = 51.55 (7)° in (II), 59.22 (12)° in (III) and 51.99 (14)° in (IV)]. Unlike (II), in which only weak intermolecular C—H...O_imide hydrogen bonding is present, the crystal packing of imides (III) and (IV) shows strong intermolecular carboxylic acid O—H...O hydrogen‐bonding associations. With (III), these involve imide O‐atom acceptors, giving one‐dimensional zigzag chains [graph‐set C(9)], while with the monohydrate (IV), the hydrogen bond involves the partially disordered water molecule which also bridges molecules through both imide and carboxy O‐atom acceptors in a cyclic R₄⁴(12) association, giving a two‐dimensional sheet structure. The structures reported here expand the structural database for compounds of this series formed from the facile reaction of cis‐cyclohexane‐1,2‐dicarboxylic anhydride with substituted anilines, in which there is a much larger incidence of cyclic imides compared to amide carboxylic acids.     

Zero‐, one‐ and two‐dimensional hydrogen‐bonded structures in the 1:1 proton‐transfer compounds of 4,5‐dichlorophthalic acid with the monocyclic heteroaromatic Lewis bases 2‐aminopyrimidine,nicotinamide and isonicotinamide

The structures of the anhydrous 1:1 proton‐transfer compounds of 4,5‐dichlorophthalic acid (DCPA) with the monocyclic heteroaromatic Lewis bases 2‐aminopyrimidine, 3‐(aminocarbonyl)pyridine (nicotinamide) and 4‐(aminocarbonyl)pyridine (isonicotinamide), namely 2‐aminopyrimidinium 2‐carboxy‐4,5‐dichlorobenzoate, C₄H₆N₃⁺·C₈H₃Cl₂O₄⁻, (I), 3‐(aminocarbonyl)pyridinium 2‐carboxy‐4,5‐dichlorobenzoate, C₆H₇N₂O⁺·C₈H₃Cl₂O₄⁻, (II), and the unusual salt adduct 4‐(aminocarbonyl)pyridinium 2‐carboxy‐4,5‐dichlorobenzoate–methyl 2‐carboxy‐4,5‐dichlorobenzoate (1/1), C₆H₇N₂O⁺·C₈H₃Cl₂O₄⁻·C₉H₆Cl₂O₄, (III), have been determined at 130 K. Compound (I) forms discrete centrosymmetric hydrogen‐bonded cyclic bis(cation–anion) units having both R₂²(8) and R₁²(4) N—H...O interactions. In (II), the primary N—H...O‐linked cation–anion units are extended into a two‐dimensional sheet structure via amide–carboxyl and amide–carbonyl N—H...O interactions. The structure of (III) reveals the presence of an unusual and unexpected self‐synthesized methyl monoester of the acid as an adduct molecule, giving one‐dimensional hydrogen‐bonded chains. In all three structures, the hydrogen phthalate anions are essentially planar with short intramolecular carboxyl–carboxylate O—H...O hydrogen bonds [O...O = 2.393 (8)–2.410 (2) Å]. This work provides examples of low‐dimensional 1:1 hydrogen‐bonded DCPA structure types, and includes the first example of a discrete cyclic `heterotetramer.' This low dimensionality in the structures of the 1:1 aromatic Lewis base salts of the parent acid is generally associated with the planar DCPA anion species.     

From α‐carbamoyl‐α‐cyano­oxiranes to 3‐halogenopyruv­amides

The crystal structures of the first stable α‐diol from the α‐halogenopyruv­amide series, 3‐chloro‐2,2‐di­hydroxy‐3‐phenyl­propan­amide, C₉H₁₀­ClNO₃, and three products [3‐(4‐chloro­phenyl)‐2‐cyano‐2,3‐epoxy­propan­amide, C₁₀H₇­ClN₂O₂, 3‐bromo‐2‐cyano‐2‐hydroxy‐3‐p‐tolyl­propan­amide, C₁₁H₁₁Br­N₂O₂, 3‐bromo‐2‐oxo‐3‐p‐tolyl­propan­amide, C₁₀H₁₀­BrNO₂] obtained during the systematic synthesis of α‐halogenopyruv­amides are reported. The crystal structures are dominated by hydrogen bonds involving an amide group. The stability of the geminal diol could be ascribed to hydrogen bonds which involve both hydroxyl groups.     

()‐5‐(4‐Methoxy­phenyl­amino­carbonyl)‐1‐aza­bi­cyclo­[3.3.0]octan‐2‐one benzene solvate

The title trans prolyl amide exists as a benzene solvate, C₁₅H₁₈N₂O₃·C₆H₆, with positional disorder of the prolyl ring. The molecular structure is influenced by a close intramolecular N—H⋯N contact that provides structural support for the intramolecular catalysis of peptidyl–prolyl cis–trans isomerization.     

Tris[N‐(4‐fluorophenyl)pyridine‐2‐carboxamidato‐κ2N,N′]cobalt(III) trihydrate: a novel meridional complex

The title complex, [Co(C₁₂H₈FN₂O)₃]·3H₂O, has been synthesized for the first time. The complex comprises three bidentate ligands containing the pyridine‐2‐carbox­amide stem. The distorted octahedral coordination around the Co atom is formed via the pyridine (py) N atom and the deprotonated amide N atom of each ligand, with the three pyridine rings in a meridional arrangement. For each ligand, the pyridine ring and the carbonyl group are nearly coplanar, with torsion angles in the range 0.4 (3)–4.8 (4)°. The Co—N_py distances [1.9258 (16)–1.9656 (17) Å] are shorter than the corresponding Co—N_amide distances [1.9372 (17)–1.9873 (15) Å]. In addition, the Co—N_py distances are closely related to the magnitudes of the chelate angles, a shorter Co—N_py distance corresponding to a larger angle. Five intermolecular hydrogen bonds, involving carbonyl O atoms of the ligands and lattice water mol­ecules, lead to the formation of a mesh structure.     

N‐(3‐Phenoxy‐4‐pyridinio)methanesulfonamidate

The title compound, C₁₂H₁₂N₂O₃S, is a strict pyridine analogue of nimesulide, a selective inhibitor of cyclooxygen­ase‐2. The structure is characterized by a pyridinium ring with a deprotonated sulfon­amide group. An intermolecular charge‐assisted hydrogen bond between these two groups is observed within the crystal packing, linking the mol­ecules into an infinite chain running along the b‐axis direction.     

2‐Acetamido‐N‐benz­yl‐2‐(methoxy­amino)acetamides: functionalized amino acid anticonvulsants

In the crystal structure of 2‐acetamido‐N‐benz­yl‐2‐(methoxy­amino)acetamide (3L), C₁₂H₁₇N₃O₃, the 2‐acetyl­amino­acetamide moiety has a linearly extended conformation, with an inter­planar angle between the two amide groups of 157.3 (1)°. In 2‐acetamido‐N‐benz­yl‐2‐[meth­oxy(meth­yl)­amino]­acetamide (3N), C₁₃H₁₉N₃O₃, the planes of the two amide groups inter­sect at an angle of 126.4 (4)°, resulting in a chain that is slightly more bent. The replacement of the methoxy­amino H atom of 3L with a methyl group to form 3N and concomitant loss of hydrogen bonding results in some positional/thermal disorder in the meth­oxy­(methyl)­amino group. In both structures, in addition to classical N—H⋯O hydrogen bonds, there are also weak non‐standard C—H⋯O hydrogen bonds. The hydrogen bonds and packing inter­actions result in planar hydro­philic and hydro­phobic areas perpendicular to the c axis in 3L and parallel to the ab plane in the N‐meth­yl derivative. Stereochemical comparisons with phenytoin have identified two O atoms and a phenyl group as mol­ecular features likely to be responsible for the anticon­vulsant activities of these compounds.     

2‐Phenyl­malon­amide

In the title compound, C₉H₁₀N₂O₂, the amide groups are rotated out of the C(ONH₂)—C(HPh)—C(ONH₂) plane by ca 25–47° and the phenyl ring is almost perpendicular to this plane. The crystal structure is stabilized by intra‐ and intermolecular N—H?O hydrogen bonds.     

catena‐Poly[[[2‐(2‐chlorophenoxy)‐N′‐(2‐oxidobenzylidene‐κO)acetohydrazidato‐κ2N′,O]copper(II)]‐μ‐morpholine‐κ2N:O]

In the title compound, {[Cu(C₁₅H₁₁ClN₂O₃)(C₄H₉NO)]_n, the Cu^II cation has square‐pyramidal geometry. The morpholine ligand serves as a bridge to link two symmetry‐related metal atoms, resulting in an infinite chain structure along the a axis. Adjacent chains are extended into a two‐dimensional layered structure via hydrogen bonds formed between morpholine and amide N atoms [N—H...N = 2.971 (3) Å].     

Green chemistry synthesis: 2‐amino‐3‐[(E)‐(2‐pyridyl)methylideneamino]but‐2‐enedinitrile monohydrate and 5‐cyano‐2‐(2‐pyridyl)‐1‐(2‐pyridylmethyl)‐1H‐imidazole‐4‐carboxamide

The title compounds, C₁₀H₉N₅O·H₂O (L1·H₂O) and C₁₆H₁₂N₆O (L2), were synthesized by solvent‐free aldol condensation at room temperature. L1, prepared by grinding picolinaldehyde with 2,3‐diamino‐3‐isocyanoacrylonitrile in a 1:1 molar ratio, crystallized as a monohydrate. L2 was prepared by grinding picolinaldehyde with 2,3‐diamino‐3‐isocyanoacrylonitrile in a 2:1 molar ratio. By varying the conditions of crystallization it was possible to obtain two polymorphs, viz. L2‐I and L2‐II; both crystallized in the monoclinic space group P2₁/c. They differ in the orientation of one pyridine ring with respect to the plane of the imidazole ring. In L2‐I, this ring is oriented towards and above the imidazole ring, while in L2‐II it is rotated away from and below the imidazole ring. In all three molecules, there is a short intramolecular N—H...N contact inherent to the planarity of the systems. In L1·H₂O, this involves an amino H atom and the C=N N atom, while in L2 it involves an amino H atom and an imidazole N atom. In the crystal structure of L1·H₂O, there are N—H...O and O—H...O intermolecular hydrogen bonds which link the molecules to form two‐dimensional networks which stack along [001]. These networks are further linked via intermolecular N—H...N(cyano) hydrogen bonds to form an extended three‐dimensional network. In the crystal structure of L2‐I, symmetry‐related molecules are linked via N—H...N hydrogen bonds, leading to the formation of dimers centred about inversion centres. These dimers are further linked via N—H...O hydrogen bonds involving the amide group, also centred about inversion centres, to form a one‐dimensional arrangement propagating in [100]. In the crystal structure of L2‐II, the presence of intermolecular N—H...O hydrogen bonds involving the amide group results in the formation of dimers centred about inversion centres. These are linked via N—H...N hydrogen bonds involving the second amide H atom and the cyano N atom, to form two‐dimensional networks in the bc plane. In L2‐I and L2‐II, C—H...π and π–π interactions are also present.