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.     

Design of two series of 1:1 cocrystals involving 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine and carboxylic acids

Two series of a total of ten cocrystals involving 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine with various carboxylic acids have been prepared and characterized by single‐crystal X‐ray diffraction. The pyrimidine unit used for the cocrystals offers two ring N atoms (positions N1 and N3) as proton‐accepting sites. Depending upon the site of protonation, two types of cations are possible [Rajam et al. (2017). Acta Cryst. C 73 , 862–868]. In a parallel arrangement, two series of cocrystals are possible depending upon the hydrogen bonding of the carboxyl group with position N1 or N3. In one series of cocrystals, i.e. 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–3‐bromothiophene‐2‐carboxylic acid (1/1), 1 , 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–5‐chlorothiophene‐2‐carboxylic acid (1/1), 2 , 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–2,4‐dichlorobenzoic acid (1/1), 3 , and 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–2‐aminobenzoic acid (1/1), 4 , the carboxyl hydroxy group (–OH) is hydrogen bonded to position N1 (O—H…N1) of the corresponding pyrimidine unit (single point supramolecular synthon). The inversion‐related stacked pyrimidines are doubly bridged by the carboxyl groups via N—H…O and O—H…N hydrogen bonds to form a large cage‐like tetrameric unit with an R₄²(20) graph‐set ring motif. These tetrameric units are further connected via base pairing through a pair of N—H…N hydrogen bonds, generating R₂²(8) motifs (supramolecular homosynthon). In the other series of cocrystals, i.e. 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–5‐methylthiophene‐2‐carboxylic acid (1/1), 5 , 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–benzoic acid (1/1), 6 , 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–2‐methylbenzoic acid (1/1), 7 , 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–3‐methylbenzoic acid (1/1), 8 , 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–4‐methylbenzoic acid (1/1), 9 , and 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–4‐aminobenzoic acid (1/1), 10 , the carboxyl group interacts with position N3 and the adjacent 4‐amino group of the corresponding pyrimidine ring via O—H…N and N—H…O hydrogen bonds to generate the robust R₂²(8) supramolecular heterosynthon. These heterosynthons are further connected by N—H…N hydrogen‐bond interactions in a linear fashion to form a chain‐like arrangement. In cocrystal 1 , a Br…Br halogen bond is present, in cocrystals 2 and 3 , Cl…Cl halogen bonds are present, and in cocrystals 5 , 6 and 7 , Cl…O halogen bonds are present. In all of the ten cocrystals, π–π stacking interactions are observed.     

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.     

(5RS)‐5‐(4‐Methoxyphenyl)‐2‐(methylsulfanyl)benzo[g]pyrimido[4,5‐b]quinoline‐4,6,11(3H,5H,12H)‐trione,with Z′ = 3, forms a three‐dimensional hydrogen‐bonded framework containing five types of hydrogen bond

The title compound, C₂₃H₁₇N₃O₄S, crystallizes with Z′ = 3 in the space group P. Two of the three independent molecules are broadly similar in terms of both their molecular conformations and their participation in hydrogen bonds, but the third molecule differs from the other two in both of these respects. The molecules are linked by a combination of N—H...O, N—H...N, C—H...O, C—H...N and C—H...π(arene) hydrogen bonds to form a continuous three‐dimensional framework structure within which a centrosymmetric six‐molecule aggregate can be identified as a key structural element.     

基于哌嗪与二羧酸/羟基羧酸的二元体系的超分子自组装

本文选择哌嗪 (pip) 为研究中心,分别和1,4-环己二甲酸 (H2chda)、间苯二甲酸(H2mpda)、6-羟基-2-萘甲酸 (Hohna)、1-羟基-2-萘甲酸 (Hshna) 进行超分子自组装,得到了四种新的氢键超分子体系：H2pip·chda (1), H2pip·2Hmpda (2), H2pip·ohna·2H2O (3),H2pip·shna (4)。单晶结构分析表明：1-3为三维氢键超分子结构,而 4为一维链状氢键结构。     

One barbiturate and two solvated thiobarbiturates containing the triply hydrogen‐bonded ADA/DAD synthon,plus one ansolvate and three solvates of their coformer 2,4‐diaminopyrimidine

A path to new synthons for application in crystal engineering is the replacement of a strong hydrogen‐bond acceptor, like a C=O group, with a weaker acceptor, like a C=S group, in doubly or triply hydrogen‐bonded synthons. For instance, if the C=O group at the 2‐position of barbituric acid is changed into a C=S group, 2‐thiobarbituric acid is obtained. Each of the compounds comprises two ADA hydrogen‐bonding sites (D = donor and A = acceptor). We report the results of cocrystallization experiments of barbituric acid and 2‐thiobarbituric acid, respectively, with 2,4‐diaminopyrimidine, which contains a complementary DAD hydrogen‐bonding site and is therefore capable of forming an ADA/DAD synthon with barbituric acid and 2‐thiobarbituric acid. In addition, pure 2,4‐diaminopyrimidine was crystallized in order to study its preferred hydrogen‐bonding motifs. The experiments yielded one ansolvate of 2,4‐diaminopyrimidine (pyrimidine‐2,4‐diamine, DAPY), C₄H₆N₄, (I), three solvates of DAPY, namely 2,4‐diaminopyrimidine–1,4‐dioxane (2/1), 2C₄H₆N₄·C₄H₈O₂, (II), 2,4‐diaminopyrimidine–N,N‐dimethylacetamide (1/1), C₄H₆N₄·C₄H₉NO, (III), and 2,4‐diaminopyrimidine–1‐methylpyrrolidin‐2‐one (1/1), C₄H₆N₄·C₅H₉NO, (IV), one salt of barbituric acid, viz. 2,4‐diaminopyrimidinium barbiturate (barbiturate is 2,4,6‐trioxopyrimidin‐5‐ide), C₄H₇N₄⁺·C₄H₃N₂O₃⁻, (V), and two solvated salts of 2‐thiobarbituric acid, viz. 2,4‐diaminopyrimidinium 2‐thiobarbiturate–N,N‐dimethylformamide (1/2) (2‐thiobarbiturate is 4,6‐dioxo‐2‐sulfanylidenepyrimidin‐5‐ide), C₄H₇N₄⁺·C₄H₃N₂O₂S⁻·2C₃H₇NO, (VI), and 2,4‐diaminopyrimidinium 2‐thiobarbiturate–N,N‐dimethylacetamide (1/2), C₄H₇N₄⁺·C₄H₃N₂O₂S⁻·2C₄H₉NO, (VII). The ADA/DAD synthon was succesfully formed in the salt of barbituric acid, i.e. (V), as well as in the salts of 2‐thiobarbituric acid, i.e. (VI) and (VII). In the crystal structures of 2,4‐diaminopyrimidine, i.e. (I)–(IV), R₂²(8) N—H…N hydrogen‐bond motifs are preferred and, in two structures, additional R₃²(8) patterns were observed.     

The hydrogen‐bonded complex bis(tert‐butylammonium) 2,6‐dichlorophenolate 2,4‐dichlorophenol–2,4‐dichlorophenolate tetrahydrofuran disolvate containing a chiral R53(10) hydrogen‐bonded ring as a supramolecular synthon

A fixed hydrogen‐bonding motif with a high probability of occurring when appropriate functional groups are involved is described as a `supramolecular hydrogen‐bonding synthon'. The identification of these synthons may enable the prediction of accurate crystal structures. The rare chiral hydrogen‐bonding motif R₅³(10) was observed previously in a cocrystal of 2,4,6‐trichlorophenol, 2,4‐dichlorophenol and dicyclohexylamine. In the title solvated salt, 2C₄H₁₂N⁺·C₆H₃Cl₂O⁻·(C₆H₃Cl₂O⁻·C₆H₄Cl₂O)·2C₄H₈O, five components, namely two tert‐butylammonium cations, one 2,4‐dichlorophenol molecule, one 2,4‐dichlorophenolate anion and one 2,6‐dichlorophenolate anion, are bound by N—H…O and O—H…O hydrogen bonds to form a hydrogen‐bonded ring, with the graph‐set motif R₅³(10), which is further associated with two pendant tetrahydrofuran molecules by N—H…O hydrogen bonds. The hydrogen‐bonded ring has internal symmetry, with a twofold axis running through the centre of the 2,6‐dichlorophenolate anion, and is isostructural with a previous and related structure formed from 2,4‐dichlorophenol, dicyclohexylamine and 2,4,6‐trichlorophenol. In the title crystal, helical columns are built by the alignment and twisting of the chiral hydrogen‐bonded rings, along and across the c axis, and successive pairs of rings are associated with each other through C—H…π interactions. Neighbouring helical columns are inversely related and, therefore, no chirality is sustained, in contrast to the previous case.     

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.     

Three closely related thienyl‐substituted 1,4‐epoxynaphtho[1,2‐b]azepines: hydrogen‐bonded assembly in one,two and three dimensions

(2R,4S)‐2‐(3‐Methylthiophen‐2‐yl)‐2,3,4,5‐tetrahydro‐1,4‐epoxynaphtho[1,2‐b]azepine, C₁₉H₁₇NOS, (I), crystallizes with a single enantiomer in each crystal, whereas its geometrical isomer (2RS,4SR)‐2‐(5‐methylthiophen‐2‐yl)‐2,3,4,5‐tetrahydro‐1,4‐epoxy‐naphtho[1,2‐b]azepine, (II), and (2RS,4SR)‐2‐(5‐bromothiophen‐2‐yl)‐2,3,4,5‐tetrahydro‐1,4‐epoxynaphtho[1,2‐b]azepine, C₁₈H₁₄BrNOS, (III), both crystallize as racemic mixtures. A combination of one C—H...O hydrogen bond and two C—H...π(arene) hydrogen bonds links the molecules of (I) into a three‐dimensional framework; the molecules of (II) are linked into a C(4)C(4)[R₂²(7)] chain of rings by a combination of C—H...N and C—H...O hydrogen bonds; and in (III), where Z′ = 2, a combination of four C—H...π(arene) hydrogen bonds and two C—H...π(thienyl) hydrogen bonds links the molecules into complex sheets. Comparisons are made with the assembly patterns in some aryl‐substituted 1,4‐epoxynaphtho[1,2‐b]azepines.     

Unexpected beauty and diversity in the structures of three homologous 4,5‐dialkoxy‐1‐ethynyl‐2‐nitrobenzenes: the subtle interplay between intermolecular C—H…O hydrogen bonds and alkyl chain length

The synthesis, ¹H and ¹³C NMR spectra, and X‐ray structures are described for three dialkoxy ethynylnitrobenzenes that differ only in the length of the alkoxy chain, namely 1‐ethynyl‐2‐nitro‐4,5‐dipropoxybenzene, C₁₄H₁₇NO₄, 1,2‐dibutoxy‐4‐ethynyl‐5‐nitrobenzene, C₁₆H₂₁NO₄, and 1‐ethynyl‐2‐nitro‐4,5‐dipentoxybenzene, C₁₈H₂₅NO₄. Despite the subtle changes in molecular structure, the crystal structures of the three compounds display great diversity. Thus, 1‐ethynyl‐2‐nitro‐4,5‐dipropoxybenzene crystallizes in the trigonal crystal system in the space group , with Z = 18, 1,2‐dibutoxy‐4‐ethynyl‐5‐nitrobenzene crystallizes in the monoclinic crystal system in the space group P 2₁/c , with Z = 4, and 1‐ethynyl‐2‐nitro‐4,5‐dipentoxybenzene crystallizes in the triclinic crystal system in the space group , with Z = 2. The crystal structure of 1‐ethynyl‐2‐nitro‐4,5‐dipropoxybenzene is dominated by planar hexamers formed by a bifurcated alkoxy sp‐C—H…O,O′ interaction, while the structure of the dibutoxy analogue is dominated by planar ribbons of molecules linked by a similar bifurcated alkoxy sp‐C—H…O,O′ interaction. In contrast, the dipentoxy analogue forms ribbons of molecules alternately connected by a self‐complementary sp‐C—H…O₂N interaction and a self‐complementary sp²‐C—H…O₂N interaction. Disordered solvent was included in the crystals of 1‐ethynyl‐2‐nitro‐4,5‐dipropoxybenzene and its contribution was removed during refinement.     

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.     

Synthesis and structures of six closely related N‐[3‐(2‐chlorobenzoyl)‐5‐ethylthiophen‐2‐yl]arylamides,together with an isolated reaction intermediate: order versus disorder,molecular conformations and hydrogen bonding in zero,one and two dimensions

Six closely related N‐[3‐(2‐chlorobenzoyl)‐5‐ethylthiophen‐2‐yl]arylamides have been synthesized and structurally characterized, together with a representative reaction intermediate. In each of N‐[3‐(2‐chlorobenzoyl)‐5‐ethylthiophen‐2‐yl]benzamide, C₂₀H₁₆ClNO₂S, (I), N‐[3‐(2‐chlorobenzoyl)‐5‐ethylthiophen‐2‐yl]‐4‐phenylbenzamide, C₂₆H₂₀ClNO₂S, (II), and 2‐bromo‐N‐[3‐(2‐chlorobenzoyl)‐5‐ethylthiophen‐2‐yl]benzamide, C₂₀H₁₅BrClNO₂S, (III), the molecules are disordered over two sets of atomic sites, with occupancies of 0.894 (8) and 0.106 (8) in (I), 0.832 (5) and 0.168 (5) in (II), and 0.7006 (12) and 0.2994 (12) in (III). In each of N‐[3‐(2‐chlorobenzoyl)‐5‐ethylthiophen‐2‐yl]‐2‐iodobenzamide, C₂₀H₁₅ClINO₂S, (IV), and N‐[3‐(2‐chlorobenzoyl)‐5‐ethylthiophen‐2‐yl]‐2‐methoxybenzamide, C₂₁H₁₈ClNO₃S, (V), the molecules are fully ordered, but in N‐[3‐(2‐chlorobenzoyl)‐5‐ethylthiophen‐2‐yl]‐2,6‐difluorobenzamide, C₂₀H₁₄ClF₂NO₂S, (VI), which crystallizes with Z′ = 2 in the space group C2/c, one of the two independent molecules is fully ordered, while the other is disordered over two sets of atomic sites having occupancies of 0.916 (3) and 0.084 (3). All of the molecules in compounds (I)–(VI) exhibit an intramolecular N—H…O hydrogen bond. The molecules of (I) and (VI) are linked by C—H…O hydrogen bonds to form finite zero‐dimensional dimers, which are cyclic in (I) and acyclic in (VI), those of (III) are linked by C—H…π(arene) hydrogen bonds to form simple chains, and those of (IV) and (V) are linked into different types of chains of rings, built in each case from a combination of C—H…O and C—H…π(arene) hydrogen bonds. Two C—H…O hydrogen bonds link the molecules of (II) into sheets containing three types of ring. In benzotriazol‐1‐yl 3,4‐dimethoxybenzoate, C₁₅H₁₃N₃O₄, (VII), the benzoate component is planar and makes a dihedral angle of 84.51 (6)° with the benzotriazole unit. Comparisons are made with related compounds.     

Five closely related 4‐chloro‐6,11‐dihydro‐5H‐benzo[b]pyrimido[5,4‐f]azepines: similar molecular structures but different supramolecular assemblies

Dibenz[b,f]azepine (DBA) is a privileged 6‐7‐6 tricyclic ring system of importance in both organic and medicinal chemistry. Benzo[b]pyrimido[5,4‐f]azepines (BPAs), which also contain a privileged 6‐7‐6 ring system, are less well investigated, probably because of a lack of straightforward and versatile methods for their synthesis. A simple and versatile synthetic approach to BPAs based on intramolecular Friedel–Crafts alkylation has been developed. A group of closely‐related benzo[b]pyrimido[5,4‐f]azepine derivatives, namely (6RS)‐4‐chloro‐6,11‐dimethyl‐6,11‐dihydro‐5H‐benzo[b]pyrimido[5,4‐f]azepine, C₁₄H₁₄ClN₃, (I), (6RS)‐4‐chloro‐8‐hydroxy‐6,11‐dimethyl‐6,11‐dihydro‐5H‐benzo[b]pyrimido[5,4‐f]azepine, C₁₄H₁₄ClN₃O, (II), (6RS)‐4‐<!?tlsb=‐0.14pt>chloro‐8‐methoxy‐6,11‐dimethyl‐6,11‐dihydro‐5H‐benzo[b]pyrimido[5,4‐f]azepine, C₁₅H₁₆ClN₃O, (III), and (6RS)‐4‐chloro‐8‐methoxy‐6,11‐dimethyl‐2‐phenyl‐6,11‐dihydro‐5H‐benzo[b]pyrimido[5,4‐f]azepine, C₂₁H₂₀ClN₃O, (IV), has been prepared and their structures compared with the recently published structure [Acosta‐Quintero et al. (2015). Eur. J. Org. Chem. pp. 5360–5369] of (6RS)‐4‐chloro‐2,6,8,11‐tetramethyl‐6,11‐dihydro‐5H‐benzo[b]pyrimido[5,4‐f]azepine, (V). All five compounds crystallize as racemic mixtures and they have very similar molecular conformations, with the azepine ring adopting a boat‐type conformation in each case, although the orientation of the methoxy substituent in each of (III) and (IV) is different. The supramolecular assemblies in (II) and (IV) depend upon hydrogen bonds of the O—H...N and C—H...π(arene) types, respectively, those in (I) and (V) depend upon π–π stacking interactions involving pairs of pyrimidine rings, and that in (III) depends upon a π–π stacking interaction involving pairs of phenyl rings. Short C—Cl...π(pyrimidine) contacts are present in (I), (II) and (IV) but not in (III) or (V).     

Solvent‐mediated pseudo‐quadruple hydrogen‐bond motifs in three lamotrigine–carboxylic acid complexes

Lamotrigine, an antiepileptic drug, has been complexed with three aromatic carboxylic acids. All three compounds crystallize with the inclusion of N,N‐dimethylformamide (DMF) solvent, viz. lamotriginium [3,5‐diamino‐6‐(2,3‐dichlorophenyl)‐1,2,4‐triazin‐2‐ium] 4‐iodobenzoate N,N‐dimethylformamide monosolvate, C₉H₈Cl₂N₅⁺·C₇H₄IO₂⁻·C₃H₇NO, (I), lamotriginium 4‐methylbenzoate N,N‐dimethylformamide monosolvate, C₉H₇Cl₂N₅⁺·C₈H₈O₂⁻·C₃H₇NO, (II), and lamotriginium 3,5‐dinitro‐2‐hydroxybenzoate N,N‐dimethylformamide monosolvate, C₉H₈Cl₂N₅⁺·C₇H₃N₂O₇⁻·C₃H₇NO, (III). In all three structures, proton transfer takes place from the acid to the lamotrigine molecule. However, in (I) and (II), the acidic H atom is disordered over two sites and there is only partial transfer of the H atom from O to N. In (III), the corresponding H atom is ordered and complete proton transfer has occurred. Lamotrigine–lamotrigine, lamotrigine–acid and lamotrigine–solvent interactions are observed in all three structures and they thereby exhibit isostructurality. The DMF solvent extends the lamotrigine–lamotrigine dimers into a pseudo‐quadruple hydrogen‐bonding motif.     

(8RS)‐4‐Amino‐6‐(4‐chlorophenyl)‐8‐(2,4‐dichlorothiazol‐5‐yl)‐8,9‐dihydro‐7H‐pyrimido[4,5‐b][1,4]diazepine N,N‐dimethylformamide monosolvate: sheets built from N—H...N and C—H...O hydrogen bonds

In the title compound, C₁₆H₁₁Cl₃N₆S·C₃H₇NO, the seven‐membered ring adopts a conformation which is close to the twist‐boat form. The molecular components are linked into sheets by a combination of two N—H...N hydrogen bonds and two C—H...O hydrogen bonds. Comparisons are made with other aminopyrimidine derivatives.     

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.     

Different patterns of supramolecular assembly in constitutionally similar 6‐arylimidazo[2,1‐b][1,3,4]thiadiazoles

Four imidazo[2,1‐b][1,3,4]thiadiazoles containing a simply‐substituted 6‐aryl group have been synthesized by reaction of 2‐amino‐1,3,4‐thiadiazoles with bromoacetylarenes using microwave irradiation and brief reaction times. 6‐(2‐Chlorophenyl)imidazo[2,1‐b][1,3,4]thiadiazole, C₁₀H₆ClN₃S, (I), 6‐(2‐chlorophenyl)‐2‐methylimidazo[2,1‐b][1,3,4]thiadiazole, C₁₁H₈ClN₃S, (II), 6‐(3,4‐dichlorophenyl)imidazo[2,1‐b][1,3,4]thiadiazole, C₁₀H₅Cl₂N₃S, (III), and 6‐(4‐fluoro‐3‐methoxyphenyl)‐2‐methylimidazo[2,1‐b][1,3,4]thiadiazole, C₁₂H₁₀FN₃OS, (IV), crystallize with Z′ values of 2, 1, 1 and 2 respectively. The molecular skeletons are all nearly planar and the dihedral angles between the imidazole and aryl rings are 1.51 (8) and 7.28 (8)° in (I), 9.65 (7)° in (II), 10.44 (8)° in (III), and 1.05 (8) and 7.21 (8)° in (IV). The molecules in (I) are linked by three independent C—H...N hydrogen bonds to form ribbons containing alternating R₂²(8) and R₄⁴(18) rings, and these ribbons are linked into a three‐dimensional array by three independent π‐stacking interactions. Both (II) and (III) contain centrosymmetric dimers formed by π‐stacking interactions but hydrogen bonds are absent, and the molecules of (IV) are linked into centrosymmetric R₂²(8) dimers by C—H...N hydrogen bonds. Comparisons are made with a number of related compounds.     

6‐Propyl‐2‐thiouracil versus 6‐methoxymethyl‐2‐thiouracil: enhancing the hydrogen‐bonded synthon motif by replacement of a methylene group with an O atom

The understanding of intermolecular interactions is a key objective of crystal engineering in order to exploit the derived knowledge for the rational design of new molecular solids with tailored physical and chemical properties. The tools and theories of crystal engineering are indispensable for the rational design of (pharmaceutical) cocrystals. The results of cocrystallization experiments of the antithyroid drug 6‐propyl‐2‐thiouracil (PTU) with 2,4‐diaminopyrimidine (DAPY), and of 6‐methoxymethyl‐2‐thiouracil (MOMTU) with DAPY and 2,4,6‐triaminopyrimidine (TAPY), respectively, are reported. PTU and MOMTU show a high structural similarity and differ only in the replacement of a methylene group (–CH₂–) with an O atom in the side chain, thus introducing an additional hydrogen‐bond acceptor in MOMTU. Both molecules contain an ADA hydrogen‐bonding site (A = acceptor and D = donor), while the coformers DAPY and TAPY both show complementary DAD sites and therefore should be capable of forming a mixed ADA/DAD synthon with each other, i.e. N—H…O, N—H…N and N—H…S hydrogen bonds. The experiments yielded one solvated cocrystal salt of PTU with DAPY, four different solvates of MOMTU, one ionic cocrystal of MOMTU with DAPY and one cocrystal salt of MOMTU with TAPY, namely 2,4‐diaminopyrimidinium 6‐propyl‐2‐thiouracilate–2,4‐diaminopyrimidine–N,N‐dimethylacetamide–water (1/1/1/1) (the systematic name for 6‐propyl‐2‐thiouracilate is 6‐oxo‐4‐propyl‐2‐sulfanylidene‐1,2,3,6‐tetrahydropyrimidin‐1‐ide), C₄H₇N₄⁺·C₇H₉N₂OS⁻·C₄H₆N₄·C₄H₉NO·H₂O, (I), 6‐methoxymethyl‐2‐thiouracil–N,N‐dimethylformamide (1/1), C₆H₈N₂O₂S·C₃H₇NO, (II), 6‐methoxymethyl‐2‐thiouracil–N,N‐dimethylacetamide (1/1), C₆H₈N₂O₂S·C₄H₉NO, (III), 6‐methoxymethyl‐2‐thiouracil–dimethyl sulfoxide (1/1), C₆H₈N₂O₂S·C₂H₆OS, (IV), 6‐methoxymethyl‐2‐thiouracil–1‐methylpyrrolidin‐2‐one (1/1), C₆H₈N₂O₂S·C₅H₉NO, (V), 2,4‐diaminopyrimidinium 6‐methoxymethyl‐2‐thiouracilate (the systematic name for 6‐methoxymethyl‐2‐thiouracilate is 4‐methoxymethyl‐6‐oxo‐2‐sulfanylidene‐1,2,3,6‐tetrahydropyrimidin‐1‐ide), C₄H₇N₄⁺·C₆H₇N₂O₂S⁻, (VI), and 2,4,6‐triaminopyrimidinium 6‐methoxymethyl‐2‐thiouracilate–6‐methoxymethyl‐2‐thiouracil (1/1), C₄H₈N₅⁺·C₆H₇N₂O₂S⁻·C₆H₈N₂O₂S, (VII). Whereas in (I) only an AA/DD hydrogen‐bonding interaction was formed, the structures of (VI) and (VII) both display the desired ADA/DAD synthon. Conformational studies on the side chains of PTU and MOMTU also revealed a significant deviation for cocrystals (VI) and (VII), leading to the desired enhancement of the hydrogen‐bond pattern within the crystal.     

Topological study of diverse hydrogen‐bonded patterns found in a system of a nickel(II) complex and the sulfate anion

A nickel(II) coordination complex, bis[2,6‐bis(1H‐benzimidazol‐2‐yl‐κN³)pyridine‐κN]nickel(II) sulfate, [Ni(C₁₉H₁₃N₅)₂]SO₄ or [Ni(H₂L)₂]SO₄, having four peripheral tetrahedrally oriented N—H donor units, combines with sulfate bridges to create hydrogen‐bonded structures of varied dimensionality. The three crystal structures reported herein in the space groups P2₁2₁2₁, I and Pccn are defined solely by strong charge‐assisted N—H…O hydrogen bonds and contain disordered guests (water and dimethylformamide) that vary in size, shape and degree of hydrophilicity. Two of the compounds are channelled solids with three‐dimensional structures, while the third is one‐dimensional in nature. In spite of their differences, all three present a striking resemblance to the previously reported anhydrous relative [Guo et al. (2011). Chin. J. Inorg. Chem. 27 , 1517–1520], which is considered as the reference framework from which all three title compounds are derived. The hydrogen‐bonded frameworks are described and compared using crystallographic and topological approaches.     

Hydrogen‐bonded two‐ and three‐dimensional polymeric structures in the ammonium salts of 3,5‐dinitrobenzoic acid, 4‐nitrobenzoic acid and 2,4‐dichlorobenzoic acid

The structures of ammonium 3,5‐dinitrobenzoate, NH₄⁺·C₇H₃N₂O₆⁻, (I), ammonium 4‐nitrobenzoate dihydrate, NH₄⁺·C₇H₄NO₄⁻·2H₂O, (II), and ammonium 2,4‐dichlorobenzoate hemihydrate, NH₄⁺·C₇H₃Cl₂O₂⁻·0.5H₂O, (III), have been determined and their hydrogen‐bonded structures are described. All three salts form hydrogen‐bonded polymeric structures, viz. three‐dimensional in (I) and two‐dimensional in (II) and (III). With (I), a primary cation–anion cyclic association is formed [graph set R₄³(10)] through N—H...O hydrogen bonds, involving a carboxylate group with both O atoms contributing to the hydrogen bonds (denoted O,O′‐carboxylate) on one side and a carboxylate group with one O atom involved in two hydrogen bonds (denoted O‐carboxylate) on the other. Structure extension involves N—H...O hydrogen bonds to both carboxylate and nitro O‐atom acceptors. With structure (II), the primary inter‐species interactions and structure extension into layers lying parallel to (001) are through conjoined cyclic hydrogen‐bonding motifs, viz.R₄³(10) (one cation, an O,O′‐carboxylate group and two water molecules) and centrosymmetric R₄²(8) (two cations and two water molecules). The structure of (III) also has conjoined R₄³(10) and centrosymmetric R₄²(8) motifs in the layered structure but these differ in that the first motif involves one cation, an O,O′‐carboxylate group, an O‐carboxylate group and one water molecule, and the second motif involves two cations and two O‐carboxylate groups. The layers lie parallel to (100). The structures of salt hydrates (II) and (III), displaying two‐dimensional layered arrays through conjoined hydrogen‐bonded nets, provide further illustration of a previously indicated trend among ammonium salts of carboxylic acids, but the anhydrous three‐dimensional structure of (I) is inconsistent with that trend.