The influence of sulfur substituents on the molecular geometry and packing of thio derivatives of N‐methylphenobarbital

The room‐temperature crystal structures of four new thio derivatives of N‐methylphenobarbital [systematic name: 5‐ethyl‐1‐methyl‐5‐phenylpyrimidine‐2,4,6(1H,3H,5H)‐trione], C₁₃H₁₄N₂O₃, are compared with the structure of the parent compound. The sulfur substituents in N‐methyl‐2‐thiophenobarbital [5‐ethyl‐1‐methyl‐5‐phenyl‐2‐thioxo‐1,2‐dihydropyrimidine‐4,6(3H,5H)‐dione], C₁₃H₁₄N₂O₂S, N‐methyl‐4‐thiophenobarbital [5‐ethyl‐1‐methyl‐5‐phenyl‐4‐thioxo‐3,4‐dihydropyrimidine‐2,6(1H,5H)‐dione], C₁₃H₁₄N₂O₂S, and N‐methyl‐2,4,6‐trithiophenobarbital [5‐ethyl‐1‐methyl‐5‐phenylpyrimidine‐2,4,6(1H,3H,5H)‐trithione], C₁₃H₁₄N₂S₃, preserve the heterocyclic ring puckering observed for N‐methylphenobarbital (a half‐chair conformation), whereas in N‐methyl‐2,4‐dithiophenobarbital [5‐ethyl‐1‐methyl‐5‐phenyl‐2,4‐dithioxo‐1,2,3,4‐tetrahydropyrimidine‐6(5H)‐one], C₁₃H₁₄N₂OS₂, significant flattening of the ring was detected. The number and positions of the sulfur substituents influence the packing and hydrogen‐bonding patterns of the derivatives. In the cases of the 2‐thio, 4‐thio and 2,4,6‐trithio derivatives, there is a preference for the formation of a ring motif of the R₂²(8) type, which is also a characteristic of N‐methylphenobarbital, whereas a C(6) chain forms in the 2,4‐dithio derivative. The preferences for hydrogen‐bond formation, which follow the sequence of acceptor position 4 > 2 > 6, confirm the differences in the nucleophilic properties of the C atoms of the heterocyclic ring and are consistent with the course of N‐methylphenobarbital thionation reactions.     

Amino‐ und halogenfunktionelle Siloxititane

Amino‐ and halofunctional Siloxititanes Amino‐di‐tert‐butylsilanol reacts with tetrabutoxititane in a molar ratio of 2:1 to give di‐n‐butoxi(bis(di‐tert‐butyl‐n‐butoxi)siloxi)titane, (C₄H₉OSi(CMe₃)₂‐O)₂Ti(OC₄H₉)₂ ( 1 ), and lithium‐di‐tert‐butylchlorosilanolate in a molar ratio of 3:1 to give n‐butoxi(tris(di‐tert‐butyl‐n‐butoxi)siloxi)titane, (H₉C₄OSi(CMe₃)₂‐O)₃TiOC₄H₉ ( 2 ). The amino‐di‐tert‐butylsilanol substitutes the four chloroatoms of TiCl₄ in the presence of triethylamine as HCl‐acceptor. The tetrakis(amino‐di‐tert‐butyl)siloxititane ( 3 ) is formed. The lithium salt of di‐tert‐butylfluorosilanol reacts with TiCl₄ in a molar ratio of 2:1 to give 1, 1, 3, 3‐tetra‐tert‐butyl‐1‐fluoro‐3‐trichlorotitoxi‐1, 3‐disiloxane, FSi(CMe₃)₂‐O‐Si(CMe₃)₂‐O‐TiCl₃ ( 4 ). In the reaction of di‐tert‐butyl‐chlorosilanol and TiCl₄, the anion [chlorosiloxi‐octa(tri‐μ²‐chlorotitanate)]^— ( 5 ) with protonated diethylether as counterion is obtained by using diethylether as HCl‐acceptor. The crystal structure determinations of 3 and 5 are reported.     

Thermal isomerization of ruthenium hydride compounds containing asymmetric bidentate pyrrole‐imine ligands

A series of ruthenium hydride compounds containing substituted bidentate pyrrole‐imine ligands were synthesized and characterized. Reacting RuHCl(CO)(PPh₃)₃ with one equivalent of [C₄H₃NH(2‐CH=NR)] in ethanol in the presence of KOH gave compounds {RuH(CO)(PPh₃)₂[C₄H₃N(2‐CH=NR)]} where trans‐Py‐Ru‐H 1, R = CH₂CH₂C₆H₉; cis‐Py‐Ru‐H 2, R = Ph‐2‐Me; and cis‐Py‐Ru‐H 3, R = C₆H₁₁. Heating trans‐Py‐Ru‐H 1 in toluene at 70°C for 12 hr resulted a thermal conversion of the trans‐Py‐Ru‐H 1 into its cis form, {RuH(CO)(PPh₃)₂[C₄H₃N(2‐CH=NCH₂CH₂C₆H₉)]} (cis‐Py‐Ru‐H 1) in very high yield. The ¹H NMR spectra of trans‐Py‐Ru‐H 1, cis‐Py‐Ru‐H 2, cis‐Py‐Ru‐H 3, and cis‐Py‐Ru‐H 1 all show a typical triplet at ca. δ–11 for the hydride. The trans and cis form indicate the relative positions of pyrrole ring and hydride. The geometries of trans‐Py‐Ru‐H 1, cis‐Py‐Ru‐H 1, and cis‐Py‐Ru‐H 3 are relatively similar showing typical octahedral geometries with two PPh₃ fragments arranged in trans positions.     

Conformation of Peptides Containing a Chiral α‐Ethylated α,α‐Disubstituted α‐Amino Acid: (S)‐α‐Ethylleucine (=(2S)‐2‐Amino‐2‐ethyl‐4‐methylpentanoic Acid) within Sequences of Dimethylglycine and Diethylglycine Residues

An optically active (S)‐α‐ethylleucine ((S)‐αEtLeu) as a chiral α‐ethylated α,α‐disubstituted α‐amino acid was synthesized by means of a chiral acetal auxiliary of (R,R)‐cyclohexane‐1,2‐diol. The chiral α‐ethylated α,α‐disubstituted amino acid (S)‐αEtLeu was introduced into the peptides constructed from 2‐aminoisobutyric acid (=dimethylglycine, Aib), and also into the peptide prepared from diethylglycine (Deg). The X‐ray crystallographic analysis revealed that both right‐handed (P) and left‐handed (M) 3₁₀‐helical structures exist in the solid state of CF₃CO‐(Aib)₂‐[(S)‐αEtLeu]‐(Aib)₂‐OEt ( 14 ) and CF₃CO‐[(S)‐αEtLeu]‐(Deg)₄‐OEt ( 18 ), respectively. The IR, CD, and ¹H‐NMR spectra indicated that the dominant conformation of pentapeptides 14 and CF₃CO‐[(S)‐αEtLeu]‐(Aib)₄‐OEt ( 16 ) in solution is a 3₁₀‐helical structure, and that of 18 in solution is a planar C₅ conformation. The conformation of peptides was also studied by molecular‐mechanics calculations.     

Extensive hydrogen and halogen bonding,and absence of intramolecular hydrogen bonding between alcohol and nitro groups in a series of endo‐nitronorbornanol compounds

The influence of the substituent at the C2 position on the hydrogen‐bonding patterns is compared for a series of five related compounds, namely (±)‐3‐exo,6‐exo‐dibromo‐5‐endo‐hydroxy‐3‐endo‐nitrobicyclo[2.2.1]heptane‐2‐exo‐carbonitrile, C₈H₈Br₂N₂O₃, (II), (±)‐3‐exo,6‐exo‐dibromo‐6‐endo‐nitro‐5‐exo‐phenylbicyclo[2.2.1]heptan‐2‐endo‐ol, C₁₃H₁₃Br₂NO₃, (III), (±)‐methyl 3‐exo,6‐exo‐dibromo‐5‐endo‐hydroxy‐3‐endo‐nitrobicyclo[2.2.1]heptane‐2‐exo‐carboxylate, C₉H₁₁Br₂NO₅, (IV), (±)‐methyl 3‐exo,6‐exo‐dibromo‐7‐diphenylmethylidene‐5‐endo‐hydroxy‐3‐endo‐nitrobicyclo[2.2.1]heptane‐2‐exo‐carboxylate, C₂₂H₁₉Br₂NO₅, (V), and (±)‐methyl 3‐exo,6‐exo‐dibromo‐5‐endo‐hydroxy‐3‐endo‐nitro‐7‐oxabicyclo[2.2.1]heptane‐2‐exo‐carboxylate, C₈H₉Br₂NO₆, (VI). The hydrogen‐bonding motif in all five compounds is a chain, formed by O—H...O hydrogen bonds in (III), (IV), (V) and (VI), and by O—H...N hydrogen bonds in (II). All compounds except (III) contain a number of Br...Br and Br...O halogen bonds that connect the chains to each other to form two‐dimensional sheets or three‐dimensional networks. None of the compounds features intramolecular hydrogen bonding between the alcohol and nitro functional groups, as was found in the related compound (±)‐methyl 3‐exo,6‐exo‐dichloro‐5‐endo‐hydroxy‐3‐endo‐nitrobicyclo[2.2.1]heptane‐2‐exo‐carboxylate, (I) [Boeyens, Denner & Michael (1984b). J. Chem. Soc. Perkin Trans. 2, pp. 767–770]. The crystal structure of (V) exhibits whole‐molecule disorder.     

Covalent‐assisted supramolecular synthesis: the effect of hydrogen bonding in cocrystals of 4‐tert‐butylbenzoic acid with isoniazid and its derivatized forms

A series of cocrystals of isoniazid and four of its derivatives have been produced with the cocrystal former 4‐tert‐butylbenzoic acid via a one‐pot covalent and supramolecular synthesis, namely 4‐tert‐butylbenzoic acid–isoniazid, C₆H₇N₃O·C₁₁H₁₄O₂, 4‐tert‐butylbenzoic acid–N′‐(propan‐2‐ylidene)isonicotinohydrazide, C₉H₁₁N₃O·C₁₁H₁₄O₂, 4‐tert‐butylbenzoic acid–N′‐(butan‐2‐ylidene)isonicotinohydrazide, C₁₀H₁₃N₃O·C₁₁H₁₄O₂, 4‐tert‐butylbenzoic acid–N′‐(diphenylmethylidene)isonicotinohydrazide, C₁₉H₁₅N₃O·C₁₁H₁₄O₂, and 4‐tert‐butylbenzoic acid–N′‐(4‐hydroxy‐4‐methylpentan‐2‐ylidene)isonicotinohydrazide, C₁₂H₁₇N₃O₂·C₁₁H₁₄O₂. The co‐former falls under the classification of a `generally regarded as safe' compound. The four derivatizing ketones used are propan‐2‐one, butan‐2‐one, benzophenone and 3‐hydroxy‐3‐methylbutan‐2‐one. Hydrogen bonds involving the carboxylic acid occur consistently with the pyridine ring N atom of the isoniazid and all of its derivatives. The remaining hydrogen‐bonding sites on the isoniazid backbone vary based on the steric influences of the derivative group. These are contrasted in each of the molecular systems.     

2,6‐Bis(azaindole)pyridine: reactivity with iron(III) and copper(II) salts

1‐[6‐(1H‐Pyrrolo[2,3‐b]pyridin‐1‐yl)pyridin‐2‐yl]‐1H‐pyrrolo[2,3‐b]pyridin‐7‐ium tetrachloridoferrate(III), (C₁₉H₁₄N₅)[FeCl₄], (II), and [2,6‐bis(1H‐pyrrolo[2,3‐b]pyridin‐1‐yl‐κN⁷)pyridine‐κN]bis(nitrato‐κO)copper(II), [Cu(NO₃)₂(C₁₉H₁₃N₅)], (III), were prepared by self‐assembly from FeCl₃·6H₂O or Cu(NO₃)₂·3H₂O and 2,6‐bis(1H‐pyrrolo[2,3‐b]pyridin‐1‐yl)pyridine [commonly called 2,6‐bis(azaindole)pyridine, bap], C₁₉H₁₃N₅, (I). Compound (I) crystallizes with Z′ = 2 in the P space group, with both independent molecules adopting a trans–trans conformation. Compound (II) is a salt complex with weak C—H...Cl interactions giving rise to a zigzag network with π‐stacking down the a axis. Complex (III) lies across a twofold rotation axis in the C2/c space group. The Cu^II center in (III) has an N₃O₂ trigonal–bipyramidal environment. The nitrate ligand coordinates in a monodentate fashion, while the bap ligand adopts a twisted tridentate binding mode. C—H...O interactions give rise to a ribbon motif.     

Conformational study of (Z)‐5‐(4‐chlorobenzylidene)‐2‐[4‐(2‐hydroxyethyl)piperazin‐1‐yl]‐3H‐imidazol‐4(5H)‐one in different environments: insight into the structural properties of bacterial efflux pump inhibitors

The 2‐amine derivatives of 5‐arylidene‐3H‐imidazol‐4(5H )‐one are a new class of bacterial efflux pump inhibitors, the chemical compounds that are able to restore antibiotic efficacy against multidrug resistant bacteria. 5‐Arylidene‐3H‐imidazol‐4(5H )‐ones with a piperazine ring at position 2 reverse the mechanisms of multidrug resistance (MDR) of the particularly dangerous Gram‐negative bacteria E. coli by inhibition of the efflux pump AcrA/AcrB/TolC (a main multidrug resistance mechanism in Gram‐negative bacteria, consisting of a membrane fusion protein, AcrA, a Resistant‐Nodulation‐Division protein, AcrB, and an outer membrane factor, TolC). In order to study the influence of the environment on the conformation of (Z )‐5‐(4‐chlorobenzylidene)‐2‐[4‐(2‐hydroxyethyl)piperazin‐1‐yl]‐3H‐imidazol‐4(5H )‐one, ( 3 ), two different salts were prepared, namely with picolinic acid {systematic name: 4‐[(Z )‐4‐(4‐chlorobenzylidene)‐5‐oxo‐3,4‐dihydro‐1H‐imidazol‐2‐yl]‐1‐(2‐hydroxyethyl)piperazin‐1‐ium pyridine‐2‐carboxylate, C₁₆H₂₀ClN₄O₂⁺·C₆H₄NO₂⁻, ( 3 a )} and 4‐nitrophenylacetic acid {systematic name: 4‐[(Z )‐4‐(4‐chlorobenzylidene)‐5‐oxo‐3,4‐dihydro‐1H‐imidazol‐2‐yl]‐1‐(2‐hydroxyethyl)piperazin‐1‐ium 2‐(4‐nitrophenyl)acetate, C₁₆H₂₀ClN₄O₂⁺·C₈H₆NO₄⁻, ( 3 b )}. The crystal structures of the new salts were determined by X‐ray diffraction. In both crystal structures, the molecule of ( 3 ) is protonated at an N atom of the piperazine ring by proton transfer from the corresponding acid. The carboxylate group of picolinate engages in hydrogen bonds with three molecules of the cation of ( 3 ), whereas the carboxylate group of 4‐nitrophenylacetate engages in hydrogen bonds with only two molecules of ( 3 ). As a consequence of these interactions, different orientations of the hydroxyethyl group of ( 3 ) are observed. The crystal structures are additionally stabilized by both C—H…N [in ( 3 a )] and C—H…O [in ( 3 a ) and ( 3 b )] intermolecular interactions. The geometry of the imidazolone fragment was compared with other crystal structures possessing this moiety. The tautomer observed in the crystal structures presented here, namely 3H‐imidazol‐4(5H )‐one [systematic name: 1H‐imidazol‐5(4H )‐one], is also that most frequently observed in other structures containing this heterocycle.     

Hydrogen‐bonding patterns in three substituted N‐benzyl‐N‐(3‐tert‐butyl‐1‐phenyl‐1H‐pyrazol‐5‐yl)acetamides

The molecules of N‐(3‐tert‐butyl‐1‐phenyl‐1H‐pyrazol‐5‐yl)‐2‐chloro‐N‐(4‐methoxybenzyl)acetamide, C₂₃H₂₆ClN₃O₂, are linked into a chain of edge‐fused centrosymmetric rings by a combination of one C—H...O hydrogen bond and one C—H...π(arene) hydrogen bond. In N‐(3‐tert‐butyl‐1‐phenyl‐1H‐pyrazol‐5‐yl)‐2‐chloro‐N‐(4‐chlorobenzyl)acetamide, C₂₂H₂₃Cl₂N₃O, a combination of one C—H...O hydrogen bond and two C—H...π(arene) hydrogen bonds, which utilize different aryl rings as the acceptors, link the molecules into sheets. The molecules of S‐[N‐(3‐tert‐butyl‐1‐phenyl‐1H‐pyrazol‐5‐yl)‐N‐(4‐methylbenzyl)carbamoyl]methyl O‐ethyl carbonodithioate, C₂₆H₃₁N₃O₂S₂, are also linked into sheets, now by a combination of two C—H...O hydrogen bonds, both of which utilize the amide O atom as the acceptor, and two C—H...π(arene) hydrogen bonds, which utilize different aryl groups as the acceptors.     

A structural study of 4‐aminoantipyrine and six of its Schiff base derivatives

Six derivatives of 4‐amino‐1,5‐dimethyl‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐3‐one (4‐aminoantipyrine), C₁₁H₁₃N₃O, (I), have been synthesized and structurally characterized to investigate the changes in the observed hydrogen‐bonding motifs compared to the original 4‐aminoantipyrine. The derivatives were synthesized from the reactions of 4‐aminoantipyrine with various aldehyde‐, ketone‐ and ester‐containing molecules, producing (Z)‐methyl 3‐[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]but‐2‐enoate, C₁₆H₁₉N₃O₃, (II), (Z)‐ethyl 3‐[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]but‐2‐enoate, C₁₇H₂₁N₃O₃, (III), ethyl 2‐[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]cyclohex‐1‐enecarboxylate, C₂₀H₂₅N₃O₃, (IV), (Z)‐ethyl 3‐[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]‐3‐phenylacrylate, C₂₂H₂₃N₃O₃, (V), 2‐cyano‐N‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)acetamide, C₁₄H₁₄N₄O₂, (VI), and (E)‐methyl 4‐{[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]methyl}benzoate, C₂₀H₁₉N₃O₃, (VII). The asymmetric units of all these compounds have one molecule on a general position. The hydrogen bonding in (I) forms chains of molecules via intermolecular N—H...O hydrogen bonds around a crystallographic sixfold screw axis. In contrast, the formation of enamines for all derived compounds except (VII) favours the formation of a six‐membered intramolecular N—H...O hydrogen‐bonded ring in (II)–(V) and an intermolecular N—H...O hydrogen bond in (VI), whereas there is an intramolecular C—H...O hydrogen bond in the structure of imine (VII). All the reported compounds, except for (II), feature π–π interactions, while C—H...π interactions are observed in (II), C—H...O interactions are observed in (I), (III), (V) and (VI), and a C—O...π interaction is observed in (II).     

A series of (E)‐5‐(arylideneamino)‐1‐tert‐butyl‐1H‐pyrrole‐3‐carbonitriles and their reduction products to secondary amines: syntheses and X‐ray structural studies

An efficent access to a series of N‐(pyrrol‐2‐yl)amines, namely (E)‐1‐tert‐butyl‐5‐[(4‐chlorobenzylidene)amino]‐1H‐pyrrole‐3‐carbonitrile, C₁₆H₁₆ClN₃, (7a), (E)‐1‐tert‐butyl‐5‐[(2,4‐dichlorobenzylidene)amino]‐1H‐pyrrole‐3‐carbonitrile, C₁₆H₁₅Cl₂N₃, (7b), (E)‐1‐tert‐butyl‐5‐[(pyridin‐4‐ylmethylene)amino]‐1H‐pyrrole‐3‐carbonitrile, C₁₅H₁₆N₄, (7c), 1‐tert‐butyl‐5‐[(4‐chlorobenzyl)amino]‐1H‐pyrrole‐3‐carbonitrile, C₁₆H₁₈ClN₃, (8a), and 1‐tert‐butyl‐5‐[(2,4‐dichlorobenzyl)amino]‐1H‐pyrrole‐3‐carbonitrile, C₁₆H₁₇Cl₂N₃, (8b), by a two‐step synthesis sequence (solvent‐free condensation and reduction) starting from 5‐amino‐1‐tert‐butyl‐1H‐pyrrole‐3‐carbonitrile is described. The syntheses proceed via isolated N‐(pyrrol‐2‐yl)imines, which are also key synthetic intermediates of other valuable compounds. The crystal structures of the reduced compounds showed a reduction in the symmetry compared with the corresponding precursors, viz. Pbcm to P from compound (7a) to (8a) and P2₁/c to P from compound (7b) to (8b), probably due to a severe change in the molecular conformations, resulting in the loss of planarity observed in the nonreduced compounds. In all of the crystals, the supramolecular assembly is controlled mainly by strong (N,C)—H…N hydrogen bonds. However, in the case of (7a)–(7c), C—H…Cl interactions are strong enough to help in the three‐dimensional architecture, as observed in Hirshfeld surface maps.     

Four novel spirooxazacamphorsultam derivatives

The chiral compounds (6aS,9S,10aR)‐11,11‐dimethyl‐5,5‐dioxo‐2,3,8,9‐tetrahydro‐6H‐6a,9‐methanooxazaolo[2,3‐i][2,1]benzisothiazol‐10(7H)‐one, C₁₂H₁₇NO₄S, (1), (7aS,10S,11aR)‐12,12‐dimethyl‐6,6‐dioxo‐3,4,9,10‐tetrahydro‐7H‐7a,10‐methano‐2H‐1,3‐oxazino[2,3‐i][2,1]benzisothiazol‐11(8H)‐one, C₁₃H₁₉NO₄S, (2), (6aS,9S,10R,10aR)‐11,11‐dimethyl‐5,5‐dioxo‐2,3,7,8,9,10‐hexahydro‐6H‐6a,9‐methanooxazolo[2,3‐i][2,1]benzisothiazol‐10‐ol, C₁₂H₁₉NO₄S, (3), and (7aS,10S,11R,11aR)‐12,12‐dimethyl‐6,6‐dioxo‐3,4,8,9,10,11‐hexahydro‐7H‐7a‐methano‐2H‐[1,3]oxazino[2,3‐i][2,1]benzisothiazol‐11‐ol, C₁₃H₂₁NO₄S, (4), consist of a camphor core with a five‐membered spirosultaoxazolidine or six‐membered spirosultaoxazine, as both their keto and hydroxy derivatives. In each structure, the molecules are linked via hydrogen bonding to the sulfonyl O atoms, forming chains in the unit‐cell b‐axis direction. The chains interconnect via weak C—H...O interactions. The keto compounds have very similar packing but represent the highest melting [507–508 K for (1)] and lowest melting [457–458 K for (2)] solids.     

Seven 3‐methylidene‐1H‐indol‐2(3H)‐ones related to the multiple‐receptor tyrosine kinase inhibitor sunitinib

The solid‐state structures of a series of seven substituted 3‐methylidene‐1H‐indol‐2(3H)‐one derivatives have been determined by single‐crystal X‐ray diffraction and are compared in detail. Six of the structures {(3Z)‐3‐(1H‐pyrrol‐2‐ylmethylidene)‐1H‐indol‐2(3H)‐one, C₁₃H₁₀N₂O, (2a); (3Z)‐3‐(2‐thienylmethylidene)‐1H‐indol‐2(3H)‐one, C₁₃H₉NOS, (2b); (3E)‐3‐(2‐furylmethylidene)‐1H‐indol‐2(3H)‐one monohydrate, C₁₃H₉NO₂·H₂O, (3a); 3‐(1‐methylethylidene)‐1H‐indol‐2(3H)‐one, C₁₁H₁₁NO, (4a); 3‐cyclohexylidene‐1H‐indol‐2(3H)‐one, C₁₄H₁₅NO, (4c); and spiro[1,3‐dioxane‐2,3′‐indolin]‐2′‐one, C₁₁H₁₁NO₃, (5)} display, as expected, intermolecular hydrogen bonding (N—H...O=C) between the 1H‐indol‐2(3H)‐one units. However, methyl 3‐(1‐methylethylidene)‐2‐oxo‐2,3‐dihydro‐1H‐indole‐1‐carboxylate, C₁₃H₁₃NO₃, (4b), a carbamate analogue of (4a) lacking an N—H bond, displays no intermolecular hydrogen bonding. The structure of (4a) contains three molecules in the asymmetric unit, while (4b) and (4c) both contain two independent molecules.     

Three styryl‐substituted tetrahydro‐1,4‐epoxy‐1‐benzazepines: configurations,conformations and hydrogen‐bonded chains

(2SR,4RS)‐7‐Chloro‐2‐exo‐[(E)‐styryl]‐2,3,4,5‐tetrahydro‐1H‐1,4‐epoxy‐1‐benzazepine, C₁₈H₁₆ClNO, (I), crystallizes as a racemic twin in the space group P2₁ and the molecules are linked into a chain of edge‐fused R₃³(9) rings by a combination of C—H...O and C—H...N hydrogen bonds. The diastereoisomer (2RS,4RS)‐7‐chloro‐2‐endo‐[(E)‐styryl]‐2,3,4,5‐tetrahydro‐1H‐1,4‐epoxy‐1‐benzazepine, (II), also crystallizes as a racemic twin, but in the space group P2₁2₁2₁, and a two‐centre C—H...N hydrogen bond and a three‐centre C—H...(O,N) hydrogen bond combine to link the molecules into a complex chain of rings. In (2R,4R)‐7‐fluoro‐2‐endo‐[(E)‐styryl]‐2,3,4,5‐tetrahydro‐1H‐1,4‐epoxy‐1‐benzazepine, C₁₈H₁₆FNO, (III), which is not isomorphous with (II), the molecules are linked by a single C—H...O hydrogen bond into simple chains, but the molecular arrangements in (II) and (III) are nonetheless very similar. The significance of this study lies in its observation of the variations in molecular configuration and conformation, and in the variation in the supramolecular aggregation, consequent upon modest changes in the peripheral substituents.     

Three novel benzothiazine‐fused triazoles as potential centrally acting muscle relaxants

The structures of the novel triazolobenzothiazines 2,4‐dihydro‐1H‐benzo[b][1,2,4]triazolo[4,3‐d][1,4]thiazin‐1‐one (IDPH‐791), C₉H₇N₃OS, (I), a potential muscle relaxant, its benzoyl derivative, 2‐(2‐oxo‐2‐phenylethyl)‐2,4‐dihydro‐1H‐benzo[b][1,2,4]triazolo[4,3‐d][1,4]thiazin‐1‐one, C₂₀H₁₇N₃O₄S, (II), and the β‐keto ester derivative, ethyl 3‐oxo‐2‐(1‐oxo‐2,4‐dihydro‐1H‐benzo[b][1,2,4]triazolo[4,3‐d][1,4]thiazin‐2‐yl)‐3‐phenylpropanoate, C₁₇H₁₃N₃O₂S, (III), are the first examples of benzothiazine‐fused triazoles in the crystallographic literature. The heterocyclic thiazine rings in all three structures adopt a distorted half‐chair conformation. Compound (III) exists in the trans‐β‐diketo form. Other than N—H...O hydrogen bonds in (I) forming dimers, no formal intermolecular hydrogen bonds are involved in the crystal packing of any of the three structures, which is dominated by C—H...O/N and π–π stacking interactions.     

Synthesis and Characterization of Heterobimetallic Tantalum–Rhodium and Tantalum–Iridium Complexes Connected by a Tantalacyclopentadiene Fragment

We report the synthesis of heterobimetallic Ta–Rh and Ta–Ir complexes bridged by a 2,5‐di‐tert‐butyltantalacyclopentadiene fragment. A mononuclear 2,5‐di‐tert‐butyltantalacyclopentadiene complex 2 was prepared by the reaction of (η²‐Me₃SiC≡CSiMe₃)TaCl₃(dme) ( 1 ) with excess amounts of 3,3‐dimethylbut‐1‐yne in the presence of AlCl₃. The tantalacyclopentadiene moiety of complex 2 served as a η⁴‐diene unit for coordinating the Rh and Ir centers; treatment of 2 with [M(μ‐Cl)(cod)]₂ (M = Rh and Ir; cod = cycloocta‐1,5‐diene) in toluene gave TaRh(μ‐C₄H₂^tBu₂)Cl₄(cod) ( 3 ) and [TaIr(μ‐C₄H₂^tBu₂)Cl₄]₂ ( 5 ), respectively. The X‐Ray diffraction study of 3 revealed a dative bond from an electron‐rich Rh toward an electron‐deficient Ta. Upon dissolving 3 in THF, [(thf)TaRh(μ‐C₄H₂^tBu₂)Cl₃]₂(μ‐Cl)₂ ( 4 ) was isolated together with free cycloocta‐1,5‐diene. When complex 5 was treated with 1,2‐bis‐(diphenylphosphino)ethane (dppe), a monomeric Ta–Ir complex, TaIr(μ‐C₄H₂^tBu₂)Cl₄(dppe) ( 6 ), was isolated. Ta–Rh and Ta–Ir heterobimetallic complexes 3 and 6 were reduced by a two‐electron process upon reaction with 2,3,5,6‐tetramethyl‐1,4‐bis(trimethylsilyl)‐1,4‐dihydropyrazine ( 7a : Si‐Me₄‐DHP) or 2,5‐dimethyl‐1,4‐bis(trimethylsilyl)‐1,4‐dihydropyrazine ( 7b : Si‐Me₂‐DHP) to afford the corresponding complexes TaM(μ‐C₄H₂^tBu₂)Cl₂(L) ( 8 : M = Rh, L = cod; 9 : M = Ir, L = dppe), where the metallacycle moiety was assigned to have a tantalacyclopentadiene fragment with a large contribution of a tantalacyclopentatriene canonical form.     

Solid‐state conformations of linear depsipeptide amides with an alternating sequence of α,α‐disubstituted α‐amino acid and α‐hydroxy acid

Depsipeptides and cyclodepsipeptides are analogues of the corresponding peptides in which one or more amide groups are replaced by ester functions. Reports of crystal structures of linear depsipeptides are rare. The crystal structures and conformational analyses of four depsipeptides with an alternating sequence of an α,α‐disubstituted α‐amino acid and an α‐hydroxy acid are reported. The molecules in the linear hexadepsipeptide amide in (S)‐Pms‐Acp‐(S)‐Pms‐Acp‐(S)‐Pms‐Acp‐NMe₂ acetonitrile solvate, C₄₇H₅₈N₄O₉·C₂H₃N, ( 3b ), as well as in the related linear tetradepsipeptide amide (S)‐Pms‐Aib‐(S)‐Pms‐Aib‐NMe₂, C₂₈H₃₇N₃O₆, ( 5a ), the diastereoisomeric mixture (S,R)‐Pms‐Acp‐(R,S)‐Pms‐Acp‐NMe₂/(R,S)‐Pms‐Acp‐(R,S)‐Pms‐Acp‐NMe₂ (1:1), C₃₂H₄₁N₃O₆, ( 5b ), and (R,S)‐Mns‐Acp‐(S,R)‐Mns‐Acp‐NMe₂, C₃₀H₃₇N₃O₆, ( 5c ) (Pms is phenyllactic acid, Acp is 1‐aminocyclopentanecarboxylic acid and Mns is mandelic acid), generally adopt a β‐turn conformation in the solid state, which is stabilized by intramolecular N—H…O hydrogen bonds. Whereas β‐turns of type I (or I′) are formed in the cases of ( 3b ), ( 5a ) and ( 5b ), which contain phenyllactic acid, the torsion angles for ( 5c ), which incorporates mandelic acid, indicate a β‐turn in between type I and type III. Intermolecular N—H…O and O—H…O hydrogen bonds link the molecules of ( 3a ) and ( 5b ) into extended chains, and those of ( 5a ) and ( 5c ) into two‐dimensional networks.     

ansa‐[(tert‐Butylamino)(isodicyclo­pentadienyl)dimethylsilane]Zr(NMe2)2 prepared by an amine‐elimination reaction

An amine‐elimination reaction was used to obtain the title compound, i.e. (N‐tert‐butyl‐N‐{[(1,2,3,3a,7a‐η)‐4,5,6,7‐tetra­hydro‐4,7‐methano‐1H‐inden‐2‐yl]­di­methyl­silyl}amido‐κN)bis(N‐methyl­methanaminato‐κN)­zirconium(IV) or [isodiCpSiMe₂N‐tert‐butyl]Zr(NMe₂)₂ (Cp is cyclo­penta­dienyl), [Zr(C₁₆H₂₅NSi)(C₂H₆N)₂], in very good yield. Treatment of isodiCpHSiMe₂NH‐tert‐butyl with Zr(NMe₂)₄ leads to the formation of a yellow solid that can be purified by sublimation. The single‐crystal structure of the product shows the exo complexation of the isodi­cyclo­penta­dienyl ligand to the Zr atom. The Cp portion of this ligand is bonded to the Zr atom in a η⁵ manner, with a Zr—Cg (Cg is the ring centroid) distance of 2.2352 (10) Å. The isodiCpSiMe₂N‐tert‐butyl ligand has a constrained geometry, which is exhibited by the small angle of 95.55 (10)° for N—Si—C_Cp.     

A trinuclear palladium(II) complex containing N,S‐coordinating 2‐(benzylsulfanyl)anilinide and 1,3‐benzothiazole‐2‐thiolate ligands with a central square‐planar PdN4 motif

The reaction of dichlorido(cod)palladium(II) (cod = 1,5‐cyclooctadiene) with 2‐(benzylsulfanyl)aniline followed by heating in N,N‐dimethylformamide (DMF) produces the linear trinuclear Pd₃ complex bis(μ₂‐1,3‐benzothiazole‐2‐thiolato)bis[μ₂‐2‐(benzylsulfanyl)anilinido]dichloridotripalladium(II) N,N‐dimethylformamide disolvate, [Pd₃(C₇H₄NS₂)₂(C₁₃H₁₂NS)₂Cl₂]·2C₃H₇NO. The molecule has symmetry and a Pd...Pd separation of 3.2012 (4) Å. The outer Pd^II atoms have a square‐planar geometry formed by an N,S‐chelating 2‐(benzylsulfanyl)anilinide ligand, a chloride ligand and the thiolate S atom of a bridging 1,3‐benzothiazole‐2‐thiolate ligand, while the central Pd^II core shows an all N‐coordinated square‐planar geometry. The geometry is perfectly planar within the PdN₄ core and the N—Pd—N bond angles differ significantly [84.72 (15)° for the N atoms of ligands coordinated to the same outer Pd atom and 95.28 (15)° for the N atoms of ligands coordinated to different outer Pd atoms]. This trinuclear Pd₃ complex is the first example of one in which 1,3‐benzothiazole‐2‐thiolate ligands are only N‐coordinated to one Pd centre. The 1,3‐benzothiazole‐2‐thiolate ligands were formed in situ from 2‐(benzylsulfanyl)aniline.     

Preparation and structural analysis of (±)‐cis‐ethyl 2‐sulfanylidenedecahydro‐1,6‐naphthyridine‐6‐carboxylate and (±)‐trans‐ethyl 2‐oxooctahydro‐1H‐pyrrolo[3,2‐c]pyridine‐5‐carboxylate

Bicycle ring closure on a mixture of (4aS,8aR)‐ and (4aR,8aS)‐ethyl 2‐oxodecahydro‐1,6‐naphthyridine‐6‐carboxylate, followed by conversion of the separated cis and trans isomers to the corresponding thioamide derivatives, gave (4aSR,8aRS)‐ethyl 2‐sulfanylidenedecahydro‐1,6‐naphthyridine‐6‐carboxylate, C₁₁H₁₈N₂O₂S. Structural analysis of this thioamide revealed a structure with two crystallographically independent conformers per asymmetric unit (Z′ = 2). The reciprocal bicycle ring closure on (3aRS,7aRS)‐ethyl 2‐oxooctahydro‐1H‐pyrrolo[3,2‐c]pyridine‐5‐carboxylate, C₁₀H₁₆N₂O₃, was also accomplished in good overall yield. Here the five‐membered ring is disordered over two positions, so that both enantiomers are represented in the asymmetric unit. The compounds act as key intermediates towards the synthesis of potential new polycyclic medicinal chemical structures.