Different molecular conformations co‐exist in each of three 2‐aryl‐N‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)acetamides: hydrogen bonding in zero,one and two dimensions

4‐Antipyrine [4‐amino‐1,5‐dimethyl‐2‐phenyl‐1H‐pyrazol‐3(2H)‐one] and its derivatives exhibit a range of biological activities, including analgesic, antibacterial and anti‐inflammatory, and new examples are always of potential interest and value. 2‐(4‐Chlorophenyl)‐N‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)acetamide, C₁₉H₁₈ClN₃O₂, (I), crystallizes with Z′ = 2 in the space group P, whereas its positional isomer 2‐(2‐chlorophenyl)‐N‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)acetamide, (II), crystallizes with Z′ = 1 in the space group C2/c; the molecules of (II) are disordered over two sets of atomic sites having occupancies of 0.6020 (18) and 0.3980 (18). The two independent molecules of (I) adopt different molecular conformations, as do the two disorder components in (II), where the 2‐chlorophenyl substituents adopt different orientations. The molecules of (I) are linked by a combination of N—H…O and C—H…O hydrogen bonds to form centrosymmetric four‐molecule aggregates, while those of (II) are linked by the same types of hydrogen bonds forming sheets. The related compound N‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)‐2‐(3‐methoxyphenyl)acetamide, C₂₀H₂₁N₃O₃, (III), is isomorphous with (I) but not strictly isostructural; again the two independent molecules adopt different molecular conformations, and the molecules are linked by N—H…O and C—H…O hydrogen bonds to form ribbons. Comparisons are made with some related structures, indicating that a hydrogen‐bonded R₂²(10) ring is the common structural motif.     

A concise and efficient synthesis of amino‐substituted (1H‐benzo[d]imidazol‐1‐yl)pyrimidine hybrids: synthetic sequence and the molecular and supramolecular structures of six examples

A concise and efficient synthesis of a series of amino‐substituted benzimidazole–pyrimidine hybrids has been developed, starting from the readily available N⁴‐(2‐aminophenyl)‐6‐methoxy‐5‐nitrosopyrimidine‐2,4‐diamine. In each of N⁵‐benzyl‐6‐methoxy‐4‐(2‐phenyl‐1H‐benzo[d]imidazol‐1‐yl)pyrimidine‐2,5‐diamine, C₂₅H₂₂N₆O, (I), 6‐methoxy‐N⁵‐(4‐methoxybenzyl)‐4‐[2‐(4‐methoxyphenyl)‐1H‐benzo[d]imidazol‐1‐yl]pyrimidine‐2,5‐diamine, C₂₇H₂₆N₆O₃, (III), 6‐methoxy‐N⁵‐(4‐nitrobenzyl)‐4‐[2‐(4‐nitrophenyl)‐1H‐benzo[d]imidazol‐1‐yl]pyrimidine‐2,5‐diamine, C₂₅H₂₀N₈O₅, (IV), the molecules are linked into three‐dimensional framework structures, using different combinations of N—H…N, N—H…O, C—H…O, C—H…N and C—H…π hydrogen bonds in each case. Oxidative cleavage of 6‐methoxy‐N⁵‐(4‐methylbenzyl)‐4‐[2‐(4‐methylphenyl)‐1H‐benzo[d]imidazol‐1‐yl]pyrimidine‐2,5‐diamine, (II), with diiodine gave 6‐methoxy‐4‐[2‐(4‐methylphenyl)‐1H‐benzo[d]imidazol‐1‐yl]pyrimidine‐2,5‐diamine, which crystallized as a monohydrate, C₁₉H₁₈N₆O·H₂O, (V), and reaction of (V) with trifluoroacetic acid gave two isomeric products, namely N‐{5‐amino‐6‐methoxy‐6‐[2‐(4‐methylphenyl)‐1H‐benzo[d]imidazol‐1‐yl]pyrimidin‐2‐yl}‐2,2,2‐trifluoroacetamide, which crystallized as an ethyl acetate monosolvate, C₂₁H₁₇F₃N₆O₂·C₄H₈O₂, (VI), and N‐{2‐amino‐6‐methoxy‐4‐[2‐(4‐methylphenyl)‐1H‐benzo[d]imidazol‐1‐yl]pyrimidin‐5‐yl}‐2,2,2‐trifluoroacetamide, which crystallized as a methanol monosolvate, C₂₁H₁₇F₃N₆O₂·CH₄O, (VIIa). For each of (V), (VI) and (VIIa), the supramolecular assembly is two‐dimensional, based on different combinations of O—H…N, N—H…O, N—H…N, C—H…O and C—H…π hydrogen bonds in each case. Comparisons are made with some related structures.     

Conversion of substituted 5‐aryloxypyrazolecarbaldehydes into reduced 3,4′‐bipyrazoles: synthesis and characterization,and the structures of four precursors and two products,and their supramolecular assembly in zero,one and two dimensions

The reaction of 5‐chloro‐3‐methyl‐1‐phenyl‐1H‐pyrazole‐4‐carbaldehyde with phenols under basic conditions yields the corresponding 5‐aryloxy derivatives; the subsequent reaction of these carbaldehydes with substituted acetophenones yields the corresponding chalcones, which in turn undergo cyclocondensation reactions with hydrazine in the presence of acetic acid to form N‐acetylated reduced bipyrazoles. Structures are reported for three 5‐aryloxycarbaldehydes and the 5‐piperidino analogue, and for two reduced bipyrazole products. 5‐(2‐Chlorophenoxy)‐3‐methyl‐1‐phenyl‐1H‐pyrazole‐4‐carbaldehyde, C₁₇H₁₃ClN₂O₂, (II), which crystallizes with Z′ = 2 in the space group P, exhibits orientational disorder of the carbaldehyde group in each of the two independent molecules. Each of 3‐methyl‐5‐(4‐nitrophenoxy)‐1‐phenyl‐1H‐pyrazole‐4‐carbaldehyde, C₁₇H₁₃N₃O₄, (IV), 3‐methyl‐5‐(naphthalen‐2‐yloxy)‐1‐phenyl‐1H‐pyrazole‐4‐carbaldehyde, C₂₁H₁₆N₂O₂, (V), and 3‐methyl‐1‐phenyl‐5‐(piperidin‐1‐yl)‐1H‐pyrazole‐4‐carbaldehyde, C₁₆H₁₉N₃O, (VI), (3RS)‐2‐acetyl‐5‐(4‐azidophenyl)‐5′‐(2‐chlorophenoxy)‐3′‐methyl‐1′‐phenyl‐3,4‐dihydro‐1′H,2H‐[3,4′‐bipyrazole] C₂₇H₂₂ClN₇O₂, (IX) and (3RS)‐2‐acetyl‐5‐(4‐azidophenyl)‐3′‐methyl‐5′‐(naphthalen‐2‐yloxy)‐1′‐phenyl‐3,4‐dihydro‐1′H,2H‐[3,4′‐bipyrazole] C₃₁H₂₅N₇O₂, (X), has Z′ = 1, and each is fully ordered. The new compounds have all been fully characterized by analysis, namely IR spectroscopy, ¹H and ¹³C NMR spectroscopy, and mass spectrometry. In each of (II), (V) and (IX), the molecules are linked into ribbons, generated respectively by combinations of C—H…N, C—H…π and C—Cl…π interactions in (II), C—H…O and C—H…π hydrogen bonds in (V), and C—H…N and C—H…O hydrogen bonds in (IX). The molecules of compounds (IV) and (IX) are both linked into sheets, by multiple C—H…O and C—H…π hydrogen bonds in (IV), and by two C—H…π hydrogen bonds in (IX). A single C—H…N hydrogen bond links the molecules of (X) into centrosymmetric dimers. Comparisons are made with the structures of some related compounds.     

A concise and versatile route to tetrahydro‐1‐benzazepines carrying [a]‐fused heterocyclic units: synthetic sequence and spectroscopic characterization,and the molecular and supramolecular structures of one intermediate and two products

A concise, efficient and versatile route from simple starting materials to tricyclic tetrahydro‐1‐benzazepines carrying [a]‐fused heterocyclic units is reported. Thus, the easily accessible methyl 2‐[(2‐allyl‐4‐chlorophenyl)amino]acetate, (I), was converted, via (2RS,4SR)‐7‐chloro‐2,3,4,5‐tetrahydro‐1,4‐epoxy‐1‐benzo[b]azepine‐2‐carboxylate, (II), to the key intermediate methyl (2RS,4SR)‐7‐chloro‐4‐hydroxy‐2,3,4,5‐tetrahydro‐1H‐benzo[b]azepine‐2‐carboxylate, (III). Chloroacetylation of (III) provided the two regioisomers methyl (2RS,4SR)‐7‐chloro‐1‐(2‐chloroacetyl)‐4‐hydroxy‐2,3,4,5‐tetrahydro‐1H‐benzo[b]azepine‐2‐carboxylate, (IVa), and methyl (2RS,4SR)‐7‐chloro‐4‐(2‐chloroacetoxy)‐2,3,4,5‐tetrahydro‐1H‐benzo[b]azepine‐2‐carboxylate, C₁₄H₁₅Cl₂NO₄, (IVb), as the major and minor products, respectively, and further reaction of (IVa) with aminoethanol gave the tricyclic target compound (4aRS,6SR)‐9‐chloro‐6‐hydroxy‐3‐(2‐hydroxyethyl)‐2,3,4a,5,6,7‐hexahydrobenzo[f]pyrazino[1,2‐a]azepine‐1,4‐dione, C₁₅H₁₇ClN₂O₄, (V). Reaction of ester (III) with hydrazine hydrate gave the corresponding carbohydrazide (VI), which, with trimethoxymethane, gave a second tricyclic target product, (4aRS,6SR)‐9‐chloro‐6‐hydroxy‐4a,5,6,7‐tetrahydrobenzo[f][1,2,4]triazino[4,5‐a]azepin‐4(3H)‐one, C₁₂H₁₂ClN₃O₂, (VII). Full spectroscopic characterization (IR, ¹H and ¹³C NMR, and mass spectrometry) is reported for each of compounds (I)–(III), (IVa), (IVb) and (V)–(VII), along with the molecular and supramolecular structures of (IVb), (V) and (VII). In each of (IVb), (V) and (VII), the azepine ring adopts a chair conformation and the six‐membered heterocyclic rings in (V) and (VII) adopt approximate boat forms. The molecules in (IVb), (V) and (VII) are linked, in each case, into complex hydrogen‐bonded sheets, but these sheets all contain a different range of hydrogen‐bond types: N—H…O, C—H…O, C—H…N and C—H…π(arene) in (IVb), multiple C—H…O hydrogen bonds in (V), and N—H…N, O—H…O, C—H…N, C—H…O and C—H…π(arene) in (VII).     

Four related benzazepine derivatives in a reaction pathway leading to a benzazepine carboxylic acid: hydrogen‐bonded assembly in zero,one, two and three dimensions

(2R*,4S*)‐Methyl 2,3,4,5‐tetrahydro‐1,4‐epoxy‐1H‐benz[b]azepine‐2‐carboxylate, C₁₂H₁₃NO₃, (I), and its reduction product (2R*,4S*)‐methyl 4‐hydroxy‐2,3,4,5‐tetrahydro‐1H‐benz[b]azepine‐2‐carboxylate, C₁₂H₁₅NO₃, (II), both crystallize as single enantiomers in the space group P2₁2₁2₁, while the hydrolysis product (2RS,4SR)‐4‐hydroxy‐2,3,4,5‐tetrahydro‐1H‐benz[b]azepine‐2‐carboxylic acid, C₁₁H₁₃NO₃, (III), and the lactone (2RS,5SR)‐8‐(trifluoromethoxy)‐5,6‐dihydro‐1H‐2,5‐methanobenz[e][1,4]oxazocin‐3(2H)‐one, C₁₂H₁₀F₃NO₃, (IV), both crystallize as racemic mixtures in the space group P2₁/c. The molecules of compound (IV) are linked into centrosymmetric R₂²(10) dimers by N—H...O hydrogen bonds, and those of compound (I) are linked into chains by C—H...π(arene) hydrogen bonds. A combination of O—H...O and O—H...N hydrogen bonds links the molecules of compound (III) into sheets containing equal numbers of R₄⁴(14) and R₄⁴(26) rings, and a combination of C—H...π(arene) hydrogen bonds and three‐centre O—H...(N,O) hydrogen bonds links the molecules of compound (II) into a three‐dimensional framework structure. Comparisons are made with some related compounds.     

4‐Styrylquinolines from cyclocondensation reactions between (2‐aminophenyl)chalcones and 1,3‐diketones: crystal structures and regiochemistry

Structures are reported for two matched sets of substituted 4‐styrylquinolines which were prepared by the formation of the heterocyclic ring in cyclocondensation reactions between 1‐(2‐aminophenyl)‐3‐arylprop‐2‐en‐1‐ones with 1,3‐dicarbonyl compounds. (E)‐3‐Acetyl‐4‐[2‐(4‐methoxyphenyl)ethenyl]‐2‐methylquinoline, C₂₁H₁₉NO₂, (I), (E)‐3‐acetyl‐4‐[2‐(4‐bromophenyl)ethenyl]‐2‐methylquinoline, C₂₀H₁₆BrNO, (II), and (E)‐3‐acetyl‐2‐methyl‐4‐{2‐[4‐(trifluoromethyl)phenyl]ethenyl}quinoline, C₂₁H₁₆F₃NO, (III), are isomorphous and in each structure the molecules are linked by a single C—H…O hydrogen bond to form C(6) chains. In (I), but not in (II) or (III), this is augmented by a C—H…π(arene) hydrogen bond to form a chain of rings; hence, (I)–(III) are not strictly isostructural. By contrast with (I)–(III), no two of ethyl (E)‐4‐[2‐(4‐methoxyphenyl)ethenyl]‐2‐methylquinoline‐3‐carboxylate, C₂₂H₂₁NO₃, (IV), ethyl (E)‐4‐[2‐(4‐bromophenyl)ethenyl]‐2‐methylquinoline‐3‐carboxylate, C₂₁H₁₈BrNO₂, (V), and ethyl (E)‐2‐methyl‐4‐{2‐[4‐(trifluoromethyl)phenyl]ethenyl}quinoline‐3‐carboxylate, C₂₂H₁₈F₃NO₂, (VI), are isomorphous. The molecules of (IV) are linked by a single C—H…O hydrogen bond to form C(13) chains, but cyclic centrosymmetric dimers are formed in both (V) and (VI). The dimer in (V) contains a C—H…π(pyridyl) hydrogen bond, while that in (VI) contains two independent C—H…O hydrogen bonds. Comparisons are made with some related structures, and both the regiochemistry and the mechanism of the heterocyclic ring formation are discussed.     

Conversion of 3‐amino‐4‐arylamino‐1H‐isochromen‐1‐ones to 1‐arylisochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐ones: synthesis,spectroscopic characterization and the structures of four products and one ring‐opened derivative

An efficient synthesis of 1‐arylisochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐ones, involving the diazotization of 3‐amino‐4‐arylamino‐1H‐isochromen‐1‐ones in weakly acidic solution, has been developed and the spectroscopic characterization and crystal structures of four examples are reported. The molecules of 1‐phenylisochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐one, C₁₅H₉N₃O₂, (I), are linked into sheets by a combination of C—H…N and C—H…O hydrogen bonds, while the structures of 1‐(2‐methylphenyl)isochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐one, C₁₆H₁₁N₃O₂, (II), and 1‐(3‐chlorophenyl)isochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐one, C₁₅H₈ClN₃O₂, (III), each contain just one hydrogen bond which links the molecules into simple chains, which are further linked into sheets by π‐stacking interactions in (II) but not in (III). In the structure of 1‐(4‐chlorophenyl)isochromeno[3,4‐d][1,2,3]triazol‐5(1H)‐one, (IV), isomeric with (III), a combination of C—H…O and C—H…π(arene) hydrogen bonds links the molecules into sheets. When compound (II) was exposed to a strong acid in methanol, quantitative conversion occurred to give the ring‐opened transesterification product methyl 2‐[4‐hydroxy‐1‐(2‐methylphenyl)‐1H‐1,2,3‐triazol‐5‐yl]benzoate, C₁₇H₁₅N₃O₃, (V), where the molecules are linked by paired O—H…O hydrogen bonds to form centrosymmetric dimers.     

Halogenated C,N‐diarylacetamides: molecular conformations and supramolecular assembly

The structures of four halogenated N,2‐diarylacetamides are reported and compared with a range of analogues. N‐(4‐Chloro‐3‐methylphenyl)‐2‐phenylacetamide, C₁₅H₁₄ClNO, (I), and N‐(4‐bromo‐3‐methylphenyl)‐2‐phenylacetamide, C₁₅H₁₄BrNO, (II), are isostructural in the space group P. The molecules of (I) and (II) are linked into chains of rings by a combination of N—H...O and C—H...π(arene) hydrogen bonds. The molecules of N‐(4‐chloro‐3‐methylphenyl)‐2‐(2,4‐dichlorophenyl)acetamide, C₁₅H₁₂Cl₃NO, (III), and N‐(4‐bromo‐3‐methylphenyl)‐2‐(2‐chlorophenyl)acetamide, C₁₅H₁₃BrClNO, (IV), are linked into simple C(4) chains by N—H...O hydrogen bonds, but significant C—H...π(arene) interactions are absent. The N‐aryl groups in compounds (III) and (IV) adopt a different orientation, by ca 180°, from that of the corresponding groups in compounds (I) and (II), but otherwise the conformations of (I)–(IV) are very similar. Comparisons are drawn between compounds (I) and (IV) and a range of analogues of the type R¹CH₂CONHR², where R² represents a halogenated aryl ring and R¹ represents either another halogenated aryl ring or a naphthalen‐1‐yl unit.     

A concise,efficient and versatile synthesis of amino‐substituted benzo[b]pyrimido[5,4‐f]azepines: synthesis and spectroscopic characterization,together with the molecular and supramolecular structures of three products and one intermediate

A concise, efficient and versatile synthesis of amino‐substituted benzo[b]pyrimido[5,4‐f]azepines is described: starting from a 5‐allyl‐4,6‐dichloropyrimidine, the synthesis involves base‐catalysed aminolysis followed by intramolecular Friedel–Crafts cyclization. Four new amino‐substituted benzo[b]pyrimido[5,4‐f]azepines are reported, and all the products and reaction intermediates have been fully characterized by IR, ¹H and ¹³C NMR spectroscopy and mass spectrometry, and the molecular and supramolecular structures of three products and one intermediate have been determined. In each of N,2,6,11‐tetramethyl‐N‐phenyl‐6,11‐dihydro‐5H‐benzo[b]pyrimido[5,4‐f]azepin‐4‐amine, C₂₂H₂₄N₅, (III), 4‐(1H‐benzo[d]imidazol‐1‐yl)‐6,11‐dimethyl‐6,11‐dihydro‐5H‐benzo[b]pyrimido[5,4‐f]azepine, which crystallizes as a 0.374‐hydrate, C₂₁H₁₉N₅·0.374H₂O, (VIIIa), and 6,7,9,11‐tetramethyl‐4‐(5‐methyl‐1H‐benzo[d]imidazol‐1‐yl)‐6,11‐dihydro‐5H‐benzo[b]pyrimido[5,4‐f]azepine, C₂₄H₂₅N₅, (VIIIc), the azepine ring adopts a boat conformation, but with a different configuration at the stereogenic centre in (VIIIc), as compared with (III) and (VIIIa). In the intermediate 5‐allyl‐6‐(1H‐benzo[d]imidazol‐1‐yl)‐N‐methyl‐N‐(4‐methylphenyl)pyrimidin‐4‐amine, C₂₂N₂₁N₅, (VIIb), the immediate precursor of 4‐(1H‐benzo[d]imidazol‐1‐yl)‐6,8,11‐trimethyl‐6,11‐dihydro‐5H‐benzo[b]pyrimido[5,4‐f]azepine, (VIIIb), the allyl group is disordered over two sets of atomic sites having occupancies of 0.688 (5) and 0.312 (5). The molecules of (III) are linked into chains by a C—H…π(pyrimidine) hydrogen bond, and those of (VIIb) are linked into complex sheets by three hydrogen bonds, one of the C—H…N type and two of C—H…π(arene) type. The molecules of the organic component in (VIIIa) are linked into a chain of rings by two C—H…π(arene) hydrogen bonds, and these chains are linked into sheets by the water components; a single weak C—H…N hydrogen bond links molecules of (VIIIc) into centrosymmetric R₂²(10) dimers. Comparisons are made with some related compounds.     

Octyl 1‐(5‐tert‐butyl‐1H‐pyrazol‐3‐yl)‐2‐(4‐chlorophenyl)‐1H‐benzimidazole‐5‐carboxylate: complex sheets built from N—H...N,C—H...N and C—H...O hydrogen bonds

In the title compound, C₂₉H₃₅ClN₄O₂, the bond lengths provide evidence for aromatic delocalization in the pyrazole ring but bond fixation in the fused imidazole ring, and the octyl chain is folded, rather than adopting an all‐trans chain‐extended conformation. A combination of N—H...N, C—H...N and C—H...O hydrogen bonds links the molecules into sheets, in which the hydrogen bonds occupy the central layer with the tert‐butyl and octyl groups arranged on either side, such that the closest contacts between adjacent sheets involve only the octyl groups. Comparisons are made with the supramolecular assembly in some simpler analogues.     

Two methyl 3‐(1H‐pyrazol‐4‐yl)octahydropyrrolo[3,4‐c]pyrrole‐1‐carboxylates form different hydrogen‐bonded sheets

In the molecules of both methyl (1RS,3SR,3aRS,6aSR)‐1‐methyl‐3‐(3‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐4,6‐dioxo‐5‐phenyloctahydropyrrolo[3,4‐c]pyrrole‐1‐carboxylate, C₂₅H₂₄N₄O₄, (I), and methyl (1RS,3SR,3aRS,6aSR)‐5‐(4‐chlorophenyl)‐1‐methyl‐3‐(3‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐4,6‐dioxooctahydropyrrolo[3,4‐c]pyrrole‐1‐carboxylate, C₂₅H₂₃ClN₄O₄, (II), the two rings of the pyrrolopyrrole fragment are both nonplanar, with conformations close to half‐chair forms. The overall conformations of the molecules of (I) and (II) are very similar, apart from the orientation of the ester function. The molecules of (I) are linked into sheets by a combination of an N—H...π(pyrrole) hydrogen bond and three independent C—H...O hydrogen bonds. The molecules of (II) are also linked into sheets, which are generated by a combination of an N—H...N hydrogen bond and two independent C—H...O hydrogen bonds, weakly augmented by a C—H...π(arene) hydrogen bond.     

A concise synthesis of a highly substituted 6‐(1H‐benzimidazol‐1‐yl)‐5‐nitrosopyrimidin‐2‐amine: synthetic sequence and the molecular and supramolecular structures of one product and two intermediates

A concise and efficient synthesis of 6‐benzimidazolyl‐5‐nitrosopyrimidines has been developed using Schiff base‐type intermediates derived from N⁴‐(2‐aminophenyl)‐6‐methoxy‐5‐nitrosopyrimidine‐2,4‐diamine. 6‐Methoxy‐N⁴‐{2‐[(4‐methylbenzylidene)amino]phenyl}‐5‐nitrosopyrimidine‐2,4‐diamine, (I), and N⁴‐{2‐[(ethoxymethylidene)amino]phenyl}‐6‐methoxy‐5‐nitrosopyrimidine‐2,4‐diamine, (III), both crystallize from dimethyl sulfoxide solution as the 1:1 solvates C₁₉H₁₈N₆O₂·C₂H₆OS, (Ia), and C₁₄H₁₆N₆O₃·C₂H₆OS, (IIIa), respectively. The interatomic distances in these intermediates indicate significant electronic polarization within the substituted pyrimidine system. In each of (Ia) and (IIIa), intermolecular N—H…O hydrogen bonds generate centrosymmetric four‐molecule aggregates. Oxidative ring closure of intermediate (I), effected using ammonium hexanitratocerate(IV), produced 4‐methoxy‐6‐[2‐(4‐methylphenyl‐1H‐benzimidazol‐1‐yl]‐5‐nitrosopyrimidin‐2‐amine, C₁₉H₁₆N₆O₂, (II) [Cobo et al. (2018). Private communication (CCDC 1830889). CCDC, Cambridge, England], where the extent of electronic polarization is much less than in (Ia) and (IIIa). A combination of N—H…N and C—H…O hydrogen bonds links the molecules of (II) into complex sheets.     

2‐Ethyl‐1‐[5‐(4‐methylphenyl)pyrazol‐3‐yl]‐3‐(thiophene‐2‐carbonyl)isothiourea: molecular ribbons containing three types of hydrogen‐bonded ring

The title compound, C₁₈H₁₈N₄OS₂, was prepared by reaction of S,S‐diethyl 2‐thenoylimidodithiocarbonate with 5‐amino‐3‐(4‐methylphenyl)‐1H‐pyrazole using microwave irradiation under solvent‐free conditions. In the molecule, the thiophene unit is disordered over two sets of atomic sites, with occupancies of 0.814 (4) and 0.186 (4), and the bonded distances provide evidence for polarization in the acylthiourea fragment and for aromatic type delocalization in the pyrazole ring. An intramolecular N—H...O hydrogen bond is present, forming an S(6) motif, and molecules are linked by N—H...O and N—H...N hydrogen bonds to form a ribbon in which centrosymmetric R₂²(4) rings, built from N—H...O hydrogen bonds and flanked by inversion‐related pairs of S(6) rings, alternate with centrosymmetric R₂²(6) rings built from N—H...N hydrogen bonds.     

The interplay of solvation,molecular conformation and supramolecular assembly in 1,1′‐({[(ethane‐1,2‐diyl)dioxy](1,2‐phenylene)}bis(methanylylidene))bis(thiosemicarbazide) and its N,N‐dimethylformamide disolvate

The wide diversity of applications of thiosemicarbazones and bis(thiosemicarbazones) has seen them used as anticancer and antitubercular agents, and as ligands in metal complexes designed to act as site‐specific radiopharmaceuticals. Molecules of 1,1′‐({[(ethane‐1,2‐diyl)dioxy](1,2‐phenylene)}bis(methanylylidene))bis(thiosemicarbazide) {alternative name: 2,2′‐[ethane‐1,2‐diylbis(oxy)]dibenzaldehyde bis(thiosemicarbazide)}, C₁₈H₂₀N₆O₂S₂, (I), lie across twofold rotation axes in the space group C2/c, with an O—C—C—O torsion angle of −59.62 (13)° and a trans‐planar arrangement of the thiosemicarbazide fragments relative to the adjacent aryl rings. The molecules of (I) are linked by N—H...S hydrogen bonds to form sheets containing R²₄(38) rings and two types of R²₂(8) ring. In the N,N‐dimethylformamide disolvate, C₁₈H₂₀N₆O₂S₂·2C₃H₇NO, (II), the independent molecular components all lie in general positions, but one of the solvent molecules is disordered over two sets of atomic sites having occupancies of 0.839 (3) and 0.161 (3). The O—C—C—O torsion angle in the ArOCH₂CH₂OAr component is −75.91 (14)° and the independent thiosemicarbazide fragments both adopt a cis‐planar arrangement relative to the adjacent aryl rings. The ArOCH₂CH₂OAr components in (II) are linked by N—H...S hydrogen bonds to form deeply puckered sheets containing R²₂(8), R²₄(8) and two types of R²₂(38) rings, and which contain cavities which accommodate all of the solvent molecules in the interior of the sheets. Comparisons are made with some related compounds.     

Synthesis of spiro[indoline‐3,3′‐pyrrolizines] by 1,3‐dipolar reactions between isatins,l‐proline and electron‐deficient alkenes

Two spiro[indoline‐3,3′‐pyrrolizine] derivatives have been synthesized in good yield with high regio‐ and stereospecificity using one‐pot reactions between readily available starting materials, namely l ‐proline, substituted 1H‐indole‐2,3‐diones and electron‐deficient alkenes. The products have been fully characterized by elemental analysis, IR and NMR spectroscopy, mass spectrometry and crystal structure analysis. In (1′RS ,2′RS ,3SR ,7a′SR )‐2′‐benzoyl‐1‐hexyl‐2‐oxo‐1′,2′,5′,6′,7′,7a′‐hexahydrospiro[indoline‐3,3′‐pyrrolizine]‐1′‐carboxylic acid, C₂₈H₃₂N₂O₄, (I), the unsubstituted pyrrole ring and the reduced spiro‐fused pyrrole ring adopt half‐chair and envelope conformations, respectively, while in (1′RS ,2′RS ,3SR ,7a′SR )‐1′,2′‐bis(4‐chlorobenzoyl)‐5,7‐dichloro‐2‐oxo‐1′,2′,5′,6′,7′,7a′‐hexahydrospiro[indoline‐3,3′‐pyrrolizine], which crystallizes as a partial dichloromethane solvate, C₂₈H₂₀Cl₄N₂O₃·0.981CH₂Cl₂, (II), where the solvent component is disordered over three sets of atomic sites, these two rings adopt envelope and half‐chair conformations, respectively. Molecules of (I) are linked by an O—H…·O hydrogen bond to form cyclic R ₆⁶(48) hexamers of (S ₆) symmetry, which are further linked by two C—H…O hydrogen bonds to form a three‐dimensional framework structure. In compound (II), inversion‐related pairs of N—H…O hydrogen bonds link the spiro[indoline‐3,3′‐pyrrolizine] molecules into simple R ₂²(8) dimers.     

Three closely related 1‐(naphthalen‐2‐yl)prop‐2‐en‐1‐ones: pseudosymmetry,disorder and supramoleular assembly mediated by C—H…π and C—Br…π interactions

It has been observed that when electron‐rich naphthyl rings are present in chalcones they can participate in π–π stacking interactions, and this can play an important role in orientating inhibitors within the active sites of enzymes, while chalcones containing heterocyclic substituents additionally exhibit fungistatic and fungicidal properties. With these considerations in mind, three new chalcones containing 2‐naphthyl substituents were prepared. 3‐(4‐Fluorophenyl)‐1‐(naphthalen‐2‐yl)prop‐2‐en‐1‐one, C₁₉H₁₃FO, (I), crystallizes with Z ′ = 2 in the space group P and the four molecules in the unit cell adopt an arrangement which resembles that in the space group P 2₁/a . Although 3‐(4‐bromophenyl)‐1‐(naphthalen‐2‐yl)prop‐2‐en‐1‐one, C₁₉H₁₃BrO, (II), with Z ′ = 1, is not isostructural with (I), the molecules of (I) and (II) adopt very similar conformations. In 1‐(naphthalen‐2‐yl)‐3‐(thiophen‐2‐yl)prop‐2‐en‐1‐one, C₁₇H₁₂OS, (III), the thiophene unit is disordered over two sets of atomic sites, with occupancies of 0.780 (3) and 0.220 (3), which are related by a near 180° rotation of the thiophene unit about its exocyclic C—C bond. The molecules of compound (I) are linked by three independent C—H…π(arene) hydrogen bonds to form centrosymmetric octamolecular aggregates, whereas the molecules of compound (II) are linked into molecular ladders by a combination of C—H…π(arene) and C—Br…π(arene) interactions, and those of compound (III) are linked into centrosymmetric dimers by C—H…π(thiophene) interactions.     

Crystal structures of functional building blocks derived from bis(benzo[b]thiophen‐2‐yl)methane

The syntheses of three bis(benzo[b]thiophen‐2‐yl)methane derivatives, namely bis(benzo[b]thiophen‐2‐yl)methanone, C₁₇H₁₀OS₂, (I), 1,1‐bis(benzo[b]thiophen‐2‐yl)‐3‐(trimethylsilyl)prop‐2‐yn‐1‐ol, C₂₂H₂₀OS₂Si, (II), and 1,1‐bis(benzo[b]thiophen‐2‐yl)prop‐2‐yn‐1‐ol, C₁₉H₁₂OS₂, (III), are described and their crystal structures discussed comparatively. The conformation of ketone (I) and the respective analogues are rather similar for most of the compounds compared. This is true for the interplanar angles, the C_aryl—C_bridge—C_aryl angles and the dihedral angles. The best resemblance is found for a bioisotere of (I), viz. 2,2′‐dinaphthyl ketone, (VII). By way of interest, the crystal packings also reveal similarities between (I) and (VII). In (I), the edge‐to‐face interactions seen between two napthyl residues in (VII) are substituted by S…π contacts between the benzo[b]thiophen‐2‐yl units in (I). In the structures of the bis(benzo[b]thiophen‐2‐yl)methanols, i.e. (II) and (III), the interplanar angles are also quite similar compared with analogues and related active pharmaceutical ingredients (APIs) containing the dithiophen‐2‐ylmethane scaffold, though the dihedral angles show a larger variability and produce unsymmetrical molecules.     

Reduced 3,4′‐bipyrazoles from a simple pyrazole precursor: synthetic sequence,molecular structures and supramolecular assembly

The reaction of 5‐chloro‐3‐methyl‐1‐phenyl‐1H‐pyrazole‐4‐carbaldehyde and N‐benzylmethylamine under microwave irradiation gives 5‐[benzyl(methyl)amino]‐3‐methyl‐1‐phenyl‐1H‐pyrazole‐4‐carbaldehyde, C₁₉H₁₉N₃O, (I). Subsequent reactions under basic conditions, between (I) and a range of acetophenones, yield the corresponding chalcones. These undergo cyclocondensation reactions with hydrazine to produce reduced bipyrazoles which can be N‐formylated with formic acid or N‐acetylated with acetic anhydride. The structures of (I) and of representative examples from this reaction sequence are reported, namely the chalcone (E )‐3‐{5‐[benzyl(methyl)amino]‐3‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl}‐1‐(4‐bromophenyl)prop‐2‐en‐1‐one, C₂₇H₂₄BrN₃O, (II), the N‐formyl derivative (3RS )‐5′‐[benzyl(methyl)amino]‐3′‐methyl‐1′,5‐diphenyl‐3,4‐dihydro‐1′H ,2H‐[3,4′‐bipyrazole]‐2‐carbaldehyde, C₂₈H₂₇N₅O, (III), and the N‐acetyl derivative (3RS )‐2‐acetyl‐5′‐[benzyl(methyl)amino]‐5‐(4‐methoxyphenyl)‐3′‐methyl‐1′‐phenyl‐3,4‐dihydro‐1′H ,2H‐[3,4′‐bipyrazole], which crystallizes as the ethanol 0.945‐solvate, C₃₀H₃₁N₅O₂·0.945C₂H₆O, (IV). There is significant delocalization of charge from the benzyl(methyl)amino substituent onto the carbonyl group in (I), but not in (II). In each of (III) and (IV), the reduced pyrazole ring is modestly puckered into an envelope conformation. The molecules of (I) are linked by a combination of C—H…N and C—H…π(arene) hydrogen bonds to form a simple chain of rings; those of (III) are linked by a combination of C—H…O and C—H…N hydrogen bonds to form sheets of R ²₂(8) and R ⁶₆(42) rings, and those of (IV) are linked by a combination of O—H…N and C—H…O hydrogen bonds to form a ribbon of edge‐fused R ²₄(16) and R ⁴₄(24) rings.     

Three tetracyclic dibenzoazepine derivatives exhibiting different molecular conformations,different patterns of intermolecular hydrogen bonding and different modes of supramolecular aggregation

The biological potential of compounds of the tricyclic dibenzo[b ,e ]azepine system has resulted in considerable synthetic efforts to develop efficient methods for the synthesis of new derivatives of this kind. (9RS ,15RS )‐9‐Ethyl‐11‐methyl‐9,13b‐dihydrodibenzo[c ,f ]thiazolo[3,2‐a ]azepin‐3(2H )‐one, C₁₉H₁₉NOS, (I), crystallizes as a kryptoracemate with Z ′ = 2 in the space group P 2₁, with one molecule each of the (9R ,15R ) and (9S ,15S ) configurations in the asymmetric unit, while (9RS ,15RS )‐9‐ethyl‐7,12‐dimethyl‐9,13b‐dihydrodibenzo[c ,f ]thiazolo[3,2‐a ]azepin‐3(2H )‐one, C₂₀H₂₁NOS, (II), crystallizes with Z ′ = 1 in the space group C 2/c . Ethyl (13RS )‐2‐chloro‐13‐ethyl‐4‐oxo‐8,13‐dihydro‐4H‐benzo[5,6]azepino[3,2,1‐ij ]quinoline‐5‐carboxylate, C₂₂H₂₀ClNO₃, (III), exhibits enantiomeric disorder in the space group P such that the reference site is occupied by the 13R and 13S enantiomers, with occupancies of 0.900 (6) and 0.100 (6). In each of the two independent molecules in (I), the five‐membered ring adopts an envelope conformation, but the corresponding ring in (II) adopts a half‐chair conformation, while the six‐membered ring in the major form of (III) adopts a twist‐boat conformation. The conformation of the seven‐membered ring in each of (I), (II) and the major form of (III) approximates to the twist‐boat form. The molecules of compound (I) are linked by two C—H…O hydrogen bonds to form two independent antiparallel C (5) chains, with each type containing only one enantiomer. These chains are linked into sheets by two C—H…π(arene) hydrogen bonds, in which the two donors are both provided by the (9R ,15R ) enantiomer and the two acceptor arene rings form part of a molecule of (9S ,15S ) configuration, precluding any additional crystallographic symmetry. The molecules of compound (II) are linked by inversion‐related C—H…π(arene) hydrogen bonds to form isolated cyclic centrosymmetric dimers. The molecules of compound (III) are linked into cyclic centrosymmetric dimers by C—H…O hydrogen bonds and these dimers are linked into chains by a π–π stacking interaction. Comparisons are made with some related structures.     

Synthesis and crystal structures of the potential tyrosinase inhibitors N‐(4‐acetylphenyl)‐2‐chloroacetamide and 2‐(4‐acetylanilino)‐2‐oxoethyl cinnamate

Substituted benzoic acid and cinnamic acid esters are of interest as tyrosinase inhibitors and the development of such inhibitors may help in diminishing many dermatological disorders. The tyrosinase enzyme has also been linked to Parkinson's disease. In view of hydroxylated compounds having ester and amide functionalities to potentially inhibit tyrosinase, we herein report the synthesis and crystal structures of two amide‐based derivatives, namely N‐(4‐acetylphenyl)‐2‐chloroacetamide, C₁₀H₁₀ClNO₂, (I), and 2‐(4‐acetylanilino)‐2‐oxoethyl cinnamate, C₁₉H₁₇NO₄, (II). In compound (I), the acetylphenyl ring and the N—(C=O)—C unit of the acetamide group are almost coplanar, with a dihedral angle of 7.39 (18)°. Instead of esterification, a cheaper and more efficient synthetic method has been developed for the preparation of compound (II). The molecular geometry of compound (II) is a V‐shape. The acetamide and cinnamate groups are almost planar, with mean deviations of 0.088 and 0.046 Å, respectively; the dihedral angle between these groups is 77.39 (7)°. The carbonyl O atoms are positioned syn and anti to the amide carbonyl O atom. In the crystals of (I) and (II), N—H…O, C—H…O and C—H…π interactions link the molecules into a three‐dimensional network.