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In the realm of organic synthesis, reagents can serve not only as solvents but also as synthons. Dimethyl sulfoxide (DMSO) is recognized for its efficiency in this dual capacity, enabling diverse chemical transformations. DMSO can generate various synthons, including methyl, methylene, methine, oxygen, and methyl sulfoxide, broadening the accessible compound repertoire. Activation of DMSO as a reagent relies heavily on synergies with secondary agents like peroxide, persulfate, or iodine. Recent years have witnessed a surge in innovative synthetic techniques harnessing the synergistic interplay of DMSO and peroxide, leading to environmentally friendly and cost-effective reactions with mild conditions. This review highlights the synergistic effects of DMSO and peroxides (up to 2023), detailing their activation mechanisms and the generation of various synthons, along with numerous reported derivatives. Although this topic has received considerable attention in recent years, there are numerous discrepancies and a plethora of possibilities yet to be explored. We anticipate that this review will significantly support researchers in advancing their innovations to a greater extent in the future. This review accentuates the synergistic effects of DMSO and peroxides like potassium persulfate (K2S2O8), sodium persulfate (Na2S2O8), ammonium persulfate ((NH4)2S2O8), hydrogen peroxide (H2O2), and tertbutyl hydroperoxide (TBHP), as well as Oxone. It highlights their collaborative role in generating diverse synthons and elucidates the mechanisms of activation. [ABSTRACT FROM AUTHOR]

The structures of three multicomponent crystals formed with imidazole‐based drugs, namely metronidazole, ketoconazole and miconazole, in conjunction with trithiocyanuric acid are characterized. Each of the obtained adducts represents a different category of crystalline molecular forms: a cocrystal, a salt and a cocrystal of salt. The structural analysis revealed that in all cases, the N—H...N hydrogen bond is responsible for the formation of acid–base pairs, regardless of whether proton transfer occurs or not, and these molecular pairs are combined to form unique supramolecular motifs by centrosymmetric N—H...S interactions between acid molecules. The complex intermolecular forces acting in characteristic patterns are discussed from the geometric and energetic perspectives, involving Hirshfeld surface analysis, pairwise energy estimation, and natural bond orbital calculations. [ABSTRACT FROM AUTHOR]

In the title compound, C14H14O3, the dihedral angle between the aromatic rings is 39.76 (9)°. In the crystal, the molecules associate to form centrosymmetric acid–acid dimers linked by pairwise O—H...O hydrogen bonds. The precision of the geometric parameters in the present single-crystal study is about an order of magnitude better than the previous powder diffraction study [Chattopadhyay et al. (2013). CrystEngComm, 15, 1077–1085].

The title compound, C15H15NO2, crystallizes with two molecules in the asymmetric unit. In the crystal, the two molecules associate to form an acid–acid dimer by pairwise O—H...O hydrogen bonds.

Trifluoromethyl group relishes a privileged position in the realm of medicinal chemistry because its incorporation into organic molecules often enhances the bioactivity by altering pharmacological profile of molecule. Trifluoromethyl‐β‐dicarbonyls have emerged as pivotal building blocks in synthetic organic chemistry due to their facile accessibility, stability and remarkable versatility. Owing to presence of nucleophilic and electrophilic sites, they offer multifunctional sites for the reaction. This review covers a meticulous exploration of their multifaceted role, encompassing an in‐depth analysis of mechanism, extensive scope, limitations and wide‐ranging applications in diverse organic synthesis, covering the literature from the 21st century. This comprehensive review encapsulates the applications of trifluoromethyl‐β‐dicarbonyls and their synthetic equivalents as precursors of complex and diverse heterocyclic scaffolds, fused heterocycles and spirocyclic compounds having medicinal and material importance. Their potent synthetic utility in cyclocondensation reactions with binucleophiles, cycloaddition reactions, C−C bond formations, asymmetric multicomponent reactions using classical/solvent‐free/catalytic synthesis have been presented. Influence of unsymmetrical trifluoromethyl‐β‐diketones on regioselectivity of transformation is also reviewed. This review will benefit the synthetic and pharmaceutical communities to explore trifluoromethyl‐β‐dicarbonyls as trifluoromethyl building blocks for fabrication of heterocyclic scaffolds having implementation into drug discovery programs in the imminent future. [ABSTRACT FROM AUTHOR]

The title compound, C13H10BrNO2, was obtained by the reaction of 2,5-dibromobenzoic acid and aniline. The molecule is twisted with a dihedral angle between the aromatic rings of 45.74 (11)° and an intramolecular N—H...O hydrogen bond is seen. In the crystal, pairwise O—H...O hydrogen bonds generate carboxylic acid inversion dimers.

Salicylic acid-nicotinamide was used as a prediction model in the hydrogen bond interactions dominating a cocrystal structure. The combined conformation of the two molecules was analyzed at the B3LYP-D3BJ and WB97M-D3BJ theoretical level. The existing hydrogen bond dimer conformations were compared with putative conformations to determine the bond energy and stability. Some parameters were assessed for predictive descriptors, such as geometric parameters, total energy, interaction energy, single hydrogen bond energy, HOMO-LUMO gap, Laplacian Bond Order, and Natural Bond Orbital. An existing conformation, SACNIC1, produced intermolecular hydrogen bond energy which was quite higher than the other conformations, including the pure homomolecular conformations of either salicylic acid or nicotinamide. The cocrystal packing formation seems to be initiated with SACNIC1 as the basic structure conformation. Furthermore, the presence of the strongest intermolecular hydrogen bond energy in SACNIC1 suggests its potential utility as a predictive descriptor. [ABSTRACT FROM AUTHOR]

This paper describes the three-step synthesis of TBS-MAC, a masked acyl cyanide (MAC) and a versatile one-carbon oxidation state three synthon. We have developed a scalable and detailed synthesis that involves: (1) acetylation of malononitrile to form the sodium enolate, (2) protonation of the enolate to form acetylmalononitrile, and (3) epoxidation of the enol, rearrangement to an unstable alcohol, and TBS-protection to form the title compound. Both the sodium enolate and acetylmalononitrile are bench-stable precursors to the intermediate hydroxymalononitrile, which can be converted to other MAC reagents beyond TBS by varying the protecting group (Ac, MOM, EE, etc.). [ABSTRACT FROM AUTHOR]

3-(2-Chloro-5-methylphenoxy)propane-1,2-diol 1 is a possible precursor in the chiral beta blocker Bupranolol synthesis. Both racemic and single-enantiomeric samples of 1 were synthesized and characterized by single crystal XRD. The absolute configuration of an (S)-1 sample was determined by data refinement (the value of the Flack parameter is 0.03(4)). Hydrogen-bonded supramolecular synthons (SMS) were identified for both crystals. In rac-1, as well as in (S)-1 crystals, one of the two main SMS is the homochiral chain C 1 1 (5):21 (⋯O1–C1–C2–O2–H2⋯). The second of the two SMSs changes is the change of chiral environment. For rac-1, this is the heterochiral chain C 3 3 (9) : { 12 / 12 / 21 } ; (⋯O2–C2–C1–O1–H1⋯O′2–H′2⋯O″1–H″1⋯), in which molecules with different configurations alternate. In (S)-1 crystals, this is the homochiral chain C 1 1 (2):11 (⋯O1–H1⋯). The results obtained once again confirm the influence of the chiral environment on the crystallization of scalarly identical molecules. [ABSTRACT FROM AUTHOR]

Tinidazole (TNZ), a 5-nitroimidazole derivative, has received increasing attention due to its pharmacological activities in treatment for amebic and parasitic infections. In this paper, we synthesized three novel drug supramolecular compounds successfully based on TNZ. The three compounds discussed were formed by TNZ and 2,6-dihydroxybenzoic acid (2,6-DHBA), 4-methylsalicylic acid (4-MAC), and 5-chloro-2-hydroxybenzoic acid (5-C-2-HBA). The N-H···O and O-H···O hydrogen bonds and weak C-H···O hydrogen bonds are the primary intermolecular forces in the construction of the three compounds. Crystal structure analysis revealed that all the compounds exhibit three-dimensional frameworks consisting of non-covalent interactions. Furthermore, six primary synthons, Ⅰ R22 (8), Ⅱ R21(6), Ⅲ R22(12), Ⅳ R33(9), Ⅴ R22(12), Ⅵ R33(9), formed through various hydrogen bonds are found in the three compounds. Moreover, the resulting pharmaceutical supramolecular compounds show improved stability. Single-crystal X-ray diffraction analysis, infrared spectroscopy (IR), element analysis, and thermogravimetric analysis (TGA) are reported. [ABSTRACT FROM AUTHOR]

Herein, three novel cocrystals of 1-hydroxy-2-naphthoic acid: tetramethylpyrazine, 1-hydroxy-2-naphthoic acid:1,10-phenanthroline, and 1-hydroxy-2-naphthoic acid:1,4-bis(imidazol-1-ylmethyl)benzene (L2) were obtained by crystallization in methanol–water mixed solvent via a slow evaporation method. The cocrystalline products 1−3 were carried out by a range of techniques, including single-crystal X-ray diffraction, Fourier transform–infrared spectroscopy, elemental analysis, and thermogravimetric testing. We analyzed the crystal structures of the cocrystals 1−3 and found that weak interactions C–H···X (X = O or π) were of great importance in the process of self-assembly as well as strong and conventional hydrogen bonds (N–H···O, O–H···N, O–H···O), leading to a stable and diverse multidimensional supramolecular architecture. It is worth noting that a series of ring motifs with different sizes were explored in the crystal structures of the above complexes, such as R22(5), R22(7), R22(8), R23(13), R24(16), R44(16), R44(22), and so on. The classical and robust supramolecular synthon intermolecular bond between acid and pyridine (acid···pyridine) heterosynthon R22(7), commonly found in organic solids containing carboxylic acids with other N-containing heteroaromatics, was further demonstrated to be involved in the construction of the hydrogen-bond networks of cocrystal 1. The thermogravimetric technique used in this study proved that the mass losses of these three cocrystals were closely related to the strength of the hydrogen bonds in the package fraction. [ABSTRACT FROM AUTHOR]

3-(2-Chloro-5-methylphenoxy)propane-1,2-diol 1 is a possible precursor in the chiral beta blocker Bupranolol synthesis. Both racemic and single-enantiomeric samples of 1 were synthesized and characterized by single crystal XRD. The absolute configuration of an (S)-1 sample was determined by data refinement (the value of the Flack parameter is 0.03(4)). Hydrogen-bonded supramolecular synthons (SMS) were identified for both crystals. In rac-1, as well as in (S)-1 crystals, one of the two main SMS is the homochiral chain C11(5):21 (⋯O1–C1–C2–O2–H2⋯). The second of the two SMSs changes is the change of chiral environment. For rac-1, this is the heterochiral chain C33(9):{12/12/21}; (⋯O2–C2–C1–O1–H1⋯O′2–H′2⋯O″1–H″1⋯), in which molecules with different configurations alternate. In (S)-1 crystals, this is the homochiral chain C11(2):11 (⋯O1–H1⋯). The results obtained once again confirm the influence of the chiral environment on the crystallization of scalarly identical molecules.

Dimethyl sulfoxide (DMSO), as extremely important aprotic polar solvent and reaction medium, has attracted widespread attention from chemists in recent years due to its wide range of uses and the multiple functions it displays in various chemical processes. Especially in the past decade, dimethyl sulfoxide has become increasingly favored as a synthon in organic chemistry, resulting in great progress in this research field. In this context, this review provides a comprehensive summary of the literature on the recent progress in organic synthesis using dimethyl sulfoxide as a synthon, covering all the reports from 1 January 2016 to 11 May 2022. This type of reaction is mainly performed by transferring one or more units of dimethyl sulfoxide, such as oxygen (–O–, =O), methyl (–CH3), methylene (–CH2–), methylidene (=CH2), methine (=CH–), donor of formylation (–CHO), sulfur (–S–), methylthio (–SMe), methyl sulfoxide (–SOMe), donor of methyl thiomethylation (–CH2SMe), or donor of methyl sulfoxide methylation (–CH2SOMe), to the target molecules. At the same time, we hope that this review will stimulate future studies and promote developments in this area. [ABSTRACT FROM AUTHOR]

• Detailed characterization of secnidazole cocrystallization with various coformers. • Identification of new solid forms of secnidazole, expanding pharmaceutical applications. • Insights into the stabilizing molecular interactions, particularly hydrogen bonding. • Utilization of 2D fingerprint plots for in-depth analysis of interaction patterns. • Examination of imidazole synthon's role as a hydrogen bond acceptor in cocrystal stability. This study investigates the cocrystallization of secnidazole (SNZ), a potent antimicrobial drug, with several coformers, overcoming the inherent stability challenges posed by its hemihydrate form to produce novel solid states. We successfully synthesized and characterized three novel cocrystals with carvacrol (CAR), fumaric acid (FMA), and 3,5-dinitrobenzoic acid (DNZ), employing synchrotron single crystal analysis to elucidate their structures. The application of Hirshfeld surface and 2D fingerprint plots further enriched our understanding of the unique packing arrangements within these cocrystals. Moreover, preliminary powder X-ray diffraction (PXRD) patterns hinted at the emergence of additional novel solid forms with salicylic acid (SLC), oxalic acid (OXA), succinic acid (SUC), citric acid (CTR), and thymol (THY). Supported by literature and a thorough analysis of molecular interactions, we propose the existence of pharmaceutical cocrystals among these newly identified solid forms. Our findings not only augment the repertoire of SNZ based pharmaceuticals but also accentuates the strategic utilization of supramolecular synthons, offering significant advancements in the understanding of novel solid form formation, and the critical role of hydrogen bonding in these processes. [Display omitted] [ABSTRACT FROM AUTHOR]

Synthon theory underlies the analysis and empirical prediction of the crystal structure. Supramolecular synthons (SMSs) formed by intermolecular hydrogen bonds, such as carboxylic R 2 2 (8) and C 1 1 (4) and alcoholic C 1 1 (2) ones, are among the most popular. The subject of this publication is the identification of specific synthons in alpha-hydroxycarboxylic acids (AHAs) crystals, in which carboxyl and alcohol fragments are present simultaneously. A series of 11 single-enantiomeric and racemic crystals of substituted lactic acids, the simplest chiral AHA family, were prepared and studied by the single-crystal X-ray diffraction (SC-XRD) method. Advanced analysis of our own and published (Cambridge Structural Database) data on the 33 crystal structures of lactic and achiral AHAs of diverse structures revealed that their supramolecular organization differs significantly from that of simple carboxylic acids. We found that in AHA crystals, hydrogen bonds RC(O)O−H···O(H)−C(R′R′′)C(O)OH (in our notation HB 12) and O=C(OH)C(R′R′′)−O−H···O=C(OH)R′ (HB 23) predominate. The frequency of intermolecular hydrogen bonds is interconnected with the frequency of SMSs. Thus, the synthons mentioned above occur but do not dominate in AHA crystals. Linear synthons C 2 2 (6):12/23 and cyclic synthons R 2 2 (10):23/23 and R 3 3 (11):12/23/23 are most often implemented. An essential role in the choice of cyclic synthons is played by the chiral characteristics of the sample. [ABSTRACT FROM AUTHOR]

Abstract Acetic acid bacteria (AAB) can selectively oxidize diols into their corresponding hydroxyacids. Notably, they can convert 1,3-propanediol (1,3-PDO) into 3-hydroxypropionic acid (3-HP), which is a promising building-block. Until now, 3-HP production with AAB is carried out in batch and using resting cells at high cell densities (up to 10 g L−1 of cell dry weight). This approach is likely limited by detrimental accumulation of the intermediate 3-hydroxypropanal (3-HPA). Herein, we investigate an alternative implementation that allows highly efficient 3-HP production with lower cell densities of growing cells and that prevents 3-HPA accumulation. First, growth and 3-HP production of Acetobacter sp. CIP 58.66 were characterized with 1,3-PDO or glycerol as growth substrate. The strain was then implemented in a bioreactor, during a sequential process where it was first cultivated on glycerol, then the precursor 1,3-PDO was continuously supplied at a varying rate, easily controlled by the pH control. Different pH set points were tested (5.0, 4.5, and 4.0). This approach used the natural resistance of acetic acid bacteria to acidic conditions. Surprisingly, when pH was controlled at 5.0, the performances achieved in terms of titer (69.76 g3-HP L−1), mean productivity (2.80 g3-HP L−1 h−1), and molar yield (1.02 mol3-HP mol−1 1,3-PDO) were comparable to results obtained with genetically improved strains at neutral pH. The present results were obtained with comparatively lower cell densities (from 0.88 to 2.08 g L−1) than previously reported. This feeding strategy could be well-suited for future scale-up, since lower cell densities imply lower process costs and energy needs.

This paper describes the three-step synthesis of TBS-MAC, a masked acyl cyanide (MAC) and a versatile one-carbon oxidation state three synthon. We have developed a scalable and detailed synthesis that involves: (1) acetylation of malononitrile to form the sodium enolate, (2) protonation of the enolate to form acetylmalononitrile, and (3) epoxidation of the enol, rearrangement to an unstable alcohol, and TBS-protection to form the title compound. Both the sodium enolate and acetylmalononitrile are bench-stable precursors to the intermediate hydroxymalononitrile, which can be converted to other MAC reagents beyond TBS by varying the protecting group (Ac, MOM, EE, etc.).

Tinidazole (TNZ), a 5-nitroimidazole derivative, has received increasing attention due to its pharmacological activities in treatment for amebic and parasitic infections. In this paper, we synthesized three novel drug supramolecular compounds successfully based on TNZ. The three compounds discussed were formed by TNZ and 2,6-dihydroxybenzoic acid (2,6-DHBA), 4-methylsalicylic acid (4-MAC), and 5-chloro-2-hydroxybenzoic acid (5-C-2-HBA). The N-H···O and O-H···O hydrogen bonds and weak C-H···O hydrogen bonds are the primary intermolecular forces in the construction of the three compounds. Crystal structure analysis revealed that all the compounds exhibit three-dimensional frameworks consisting of non-covalent interactions. Furthermore, six primary synthons, Ⅰ R22 (8), Ⅱ R21(6), Ⅲ R22(12), Ⅳ R33(9), Ⅴ R22(12), Ⅵ R33(9), formed through various hydrogen bonds are found in the three compounds. Moreover, the resulting pharmaceutical supramolecular compounds show improved stability. Single-crystal X-ray diffraction analysis, infrared spectroscopy (IR), element analysis, and thermogravimetric analysis (TGA) are reported.

• Novel poly-thiolactone synthesis with endocyclic ether, polyether, and lactone groups. • Controlled thioester bond formation using diacyl chlorides and organometallic tin compounds. • Preparation of diverse polythiolactones including cyclo and spiro compounds. • Single-crystal X-ray diffraction reveals structural characteristics based on ring size and functional groups. • Crystal packing governed by C-H···O hydrogen bonding and van der Waals interactions, forming unique tubular arrangements. The synthesis and isolation of new thiolactone species containing endocyclic ether, polyether, and lactone groups were designed using the reaction between diacyl chlorides with organometallic tin compounds as a template for controlled thioester bond formation. Thus, eight polythiolactones, including cyclo and spiro compounds with different ring sizes and functional groups were prepared, namely 1-oxa-4,9-dithiacycloundecane-5,8-dione (1a), 1-oxa-4,10-dithiacyclododecane-5,9-dione (1b), 1,4-dioxa-7,12-dithiacyclotetradecane-8,11-dione (2a), 1,4-dioxa-7,13-dithiacyclopentaecane-8,12-dione (2b), 2,15,19,32-tetraoxa-6,11,23,28-tetrathia-spiro[16.16]tritriacontane 3,7,10,14,20,24,27,31-octaone (3a), 2,16,20,34-tetraoxa-6,12,24,30-tetrathia-spiro[17.17]pentatriacontan-3,7,11,15,21,25,29,33-octaone (3b), 9,12,25,28-tetraoxa-6,15,22,31-tetratia-1(1,4),17(1,4)-diphenylcyclodotriacontane-5,16,21,32-tetraone (2c), and 2,17,21,36-tetraoxo-6,13,25,32-tetrathia-8(1,4)27(1,4)-diphenyl-spiro[18-18]heptatriacontane-3,7,12,16,22,26,31,35-octaone (3c). The structural characteristics of the eight closely related derivatives were determined by examining the impact of ring size and functional groups, through single-crystal X-ray diffraction techniques. The crystal packing of these polythiolactones was found to be mainly governed by weak C-H···O hydrogen bonding and van der Waals interactions, resulting in partially overlapping tubular arrangements. Hirshfeld analysis was performed to investigate the crystal packing and intermolecular interactions. The results of this study show the possibility of forming 3D tubular arrangements using polythiolactones with various endocyclic groups, including both flexible and rigid spacers. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • α– and β–cyanovinyl ions and their isomeric structures were examined theoretically. • The α–cyanovinyl radical corresponds to the lowest energy neutral isomer. • The most stable anionic isomer corresponds to α–cyanovinyl (H 2 CCCN)– system. • The α–cyanovinyl anion is proposed to be a valuable synthon in organic synthesis. Using ab initio methods and flexible basis sets we examined neutral, cationic and anionic α– and β–cyanovinyl systems and their isomeric structures to explore the possibility of their serving as synthons. The structures and relative stability of lowest energy isomers matching the (C 3 H 2 N)0/+/– formulas were investigated and discussed. The α–cyanovinyl form was identified as the most stable structure in the case of neutral radical and closed-shell anion, whereas the (HC C C NH)+ structure, lacking a vinylic-type structural motif, was found to represent the lowest energy isomer of the cation. Regardless of the total system charge, the β–cyanovinyl isomers were found to correspond to higher energy isomers. The electronic and thermodynamic stability of the α–cyanovinyl anion was confirmed, suggesting its potential as a promising candidate for serving as a logical synthon in synthesis planning, thereby eliminating the need for substituting it with a synthetic equivalent. [ABSTRACT FROM AUTHOR]

The structures of novel cocrystals of 4‐nitropyridine N‐oxide with benzenesulfonamide derivatives, namely, 4‐nitrobenzenesulfonamide–4‐nitropyridine N‐oxide (1/1), C5H4N2O3·C6H6N2O4S, and 4‐chlorobenzenesulfonamide–4‐nitropyridine N‐oxide (1/1), C6H6ClNO2S·C5H4N2O3, are stabilized by N—H...O hydrogen bonds, with the sulfonamide group acting as a proton donor. The O atoms of the N‐oxide and nitro groups are acceptors in these interactions. The latter is a double acceptor of bifurcated hydrogen bonds. Previous studies on similar crystal structures indicated competition between these functional groups in the formation of hydrogen bonds, with the priority being for the N‐oxide group. In contrast, the present X‐ray studies indicate the existence of a hydrogen‐bonding synthon including N—H...O(N‐oxide) and N—H...O(nitro) bridges. We present here a more detailed analysis of the N‐oxide–sulfonamide–nitro N—H...O ternary complex with quantum theory computations and the Quantum Theory of Atoms in Molecules (QTAIM) approach. Both interactions are present in the crystals, but the O atom of the N‐oxide group is found to be a more effective proton acceptor in hydrogen bonds, with an interaction energy about twice that of the nitro‐group O atoms. [ABSTRACT FROM AUTHOR]

Herein, three novel cocrystals of 1-hydroxy-2-naphthoic acid: tetramethylpyrazine, 1-hydroxy-2-naphthoic acid:1,10-phenanthroline, and 1-hydroxy-2-naphthoic acid:1,4-bis(imidazol-1-ylmethyl)benzene (L2) were obtained by crystallization in methanol–water mixed solvent via a slow evaporation method. The cocrystalline products 1−3 were carried out by a range of techniques, including single-crystal X-ray diffraction, Fourier transform–infrared spectroscopy, elemental analysis, and thermogravimetric testing. We analyzed the crystal structures of the cocrystals 1−3 and found that weak interactions C–H···X (X = O or π) were of great importance in the process of self-assembly as well as strong and conventional hydrogen bonds (N–H···O, O–H···N, O–H···O), leading to a stable and diverse multidimensional supramolecular architecture. It is worth noting that a series of ring motifs with different sizes were explored in the crystal structures of the above complexes, such as R22(5), R22(7), R22(8), R23(13), R24(16), R44(16), R44(22), and so on. The classical and robust supramolecular synthon intermolecular bond between acid and pyridine (acid···pyridine) heterosynthon R22(7), commonly found in organic solids containing carboxylic acids with other N-containing heteroaromatics, was further demonstrated to be involved in the construction of the hydrogen-bond networks of cocrystal 1. The thermogravimetric technique used in this study proved that the mass losses of these three cocrystals were closely related to the strength of the hydrogen bonds in the package fraction.

The title compound, C 15 H 15 NO 2 , crystallizes with two mol-ecules in the asymmetric unit. In the crystal, the two mol-ecules associate to form an acid-acid dimer by pairwise O-H⋯O hydrogen bonds., (© Zhang and Long 2024.)

In the title compound, C 14 H 14 O 3 , the dihedral angle between the aromatic rings is 39.76 (9)°. In the crystal, the mol-ecules associate to form centrosymmetric acid-acid dimers linked by pairwise O-H⋯O hydrogen bonds. The precision of the geometric parameters in the present single-crystal study is about an order of magnitude better than the previous powder diffraction study [Chattopadhyay et al. (2013 ▸). CrystEngComm , 15 , 1077-1085]., (© Song and Long 2024.)

Nowadays, application of vinylazides as precursors is a key method for the construction of N-heterocycles in organic synthesis. These versatile three-atom synthons can be converted into intermediates such as 2H-azirines, iminyl radicals, iminyl metal complexes, iminyl inions and nitrilium ions that subsequently afford a wide range of polyfunctional cyclic nitrogen-containing compounds. In this review, the reactions of vinylazides leading to these products (in the last decade) are categorized based on the types of the resulting N-heterocyclic rings and a brief and concise description of the reaction mechanisms is presented. [ABSTRACT FROM AUTHOR]

Cocrystallisation of butanoic acid (BA), pentanoic acid (PA), and eicosanoic acid (EA) with 4,4'-azopyridine (azp) and trans-1,2-bis(4-pyridyl)ethylene (bpe) results in 2:1 lamellar cocrystals. All cocrystals display the OH···Npyridyl seven-membered ring supramolecular synthon however, each cocrystal responds differently upon heating. Positive thermal expansion (PTE) occurs along the c-axis due to π···π stacking in the isostructural BA cocrystals, while the PA cocrystals are not isostructural and display a mixture of anti and gauche conformations of the acid chains because of the length mismatch with the coformer. PA2·azp displays negative thermal expansion (NTE) of the intrasynthon C···O hydrogen bond. The two EA cocrystals both display c-axis elongation on warming due to the expansion of the distance between the alkyl chains. The expansion by more than 1 Å in EA2·azp is highly anisotropic, however, there is much less c-axis expansion in EA2·bpe. [ABSTRACT FROM AUTHOR]

Acetic acid bacteria (AAB) can selectively oxidize diols into their corresponding hydroxyacids. Notably, they can convert 1,3-propanediol (1,3-PDO) into 3-hydroxypropionic acid (3-HP), which is a promising building-block. Until now, 3-HP production with AAB is carried out in batch and using resting cells at high cell densities (up to 10 g L−1 of cell dry weight). This approach is likely limited by detrimental accumulation of the intermediate 3-hydroxypropanal (3-HPA). Herein, we investigate an alternative implementation that allows highly efficient 3-HP production with lower cell densities of growing cells and that prevents 3-HPA accumulation. First, growth and 3-HP production of Acetobacter sp. CIP 58.66 were characterized with 1,3-PDO or glycerol as growth substrate. The strain was then implemented in a bioreactor, during a sequential process where it was first cultivated on glycerol, then the precursor 1,3-PDO was continuously supplied at a varying rate, easily controlled by the pH control. Different pH set points were tested (5.0, 4.5, and 4.0). This approach used the natural resistance of acetic acid bacteria to acidic conditions. Surprisingly, when pH was controlled at 5.0, the performances achieved in terms of titer (69.76 g3-HP L−1), mean productivity (2.80 g3-HP L−1 h−1), and molar yield (1.02 mol3-HP mol−11,3-PDO) were comparable to results obtained with genetically improved strains at neutral pH. The present results were obtained with comparatively lower cell densities (from 0.88 to 2.08 g L−1) than previously reported. This feeding strategy could be well-suited for future scale-up, since lower cell densities imply lower process costs and energy needs. [ABSTRACT FROM AUTHOR]

Synthon theory underlies the analysis and empirical prediction of the crystal structure. Supramolecular synthons (SMSs) formed by intermolecular hydrogen bonds, such as carboxylic R22(8) and C11(4) and alcoholic C11(2) ones, are among the most popular. The subject of this publication is the identification of specific synthons in alpha-hydroxycarboxylic acids (AHAs) crystals, in which carboxyl and alcohol fragments are present simultaneously. A series of 11 single-enantiomeric and racemic crystals of substituted lactic acids, the simplest chiral AHA family, were prepared and studied by the single-crystal X-ray diffraction (SC-XRD) method. Advanced analysis of our own and published (Cambridge Structural Database) data on the 33 crystal structures of lactic and achiral AHAs of diverse structures revealed that their supramolecular organization differs significantly from that of simple carboxylic acids. We found that in AHA crystals, hydrogen bonds RC(O)O−H···O(H)−C(R′R′′)C(O)OH (in our notation HB 12) and O=C(OH)C(R′R′′)−O−H···O=C(OH)R′ (HB 23) predominate. The frequency of intermolecular hydrogen bonds is interconnected with the frequency of SMSs. Thus, the synthons mentioned above occur but do not dominate in AHA crystals. Linear synthons C22(6):12/23 and cyclic synthons R22(10):23/23 and R33(11):12/23/23 are most often implemented. An essential role in the choice of cyclic synthons is played by the chiral characteristics of the sample.

The crystal structures of rubescin D (1, C26H30O5) and monadelphin A (2, C30H36O11), bioactive molecules of the vilasinin and gedunin classes of limonoids, respectively, are reported for the first time and the synthons affecting their crystal packings are analyzed on the basis of their occurrences in molecules in the Cambridge Structural Database that share the same moieties. Rubescin D, 1, crystallizes in the space group P21 and its molecular structure consists of three six‐membered rings A, C and D having, respectively, envelope, twist‐boat and half‐chair conformations, and three five‐membered rings with half‐chair (B and E) and planar conformations (F). Many synthons found in the crystal packing of 1 are in agreement with expectations derived from molecules displaying the same moieties. However, the secondary alcohol–ketone O—H...O=C synthon, which has a low occurrence (2.9%), contributes much to the layered packing, while the furan–ketone Csp2—H...O=C and secondary alcohol–epoxide O—H...OC2 synthons usually found in these compounds (occurrences of 20.6 and 17.6%, respectively) are missing. The packing of 1 is close to that of ceramicine B (3), but is completely different from that of TS3 (4), suggesting that the absence of the epoxide group in 3 would have favoured the furan–secondary alcohol Csp2—H...OH synthon and that the missing hydroxy group in 4, a strong hydrogen‐bond donor, would have favoured the involvement of water molecules in the crystal packing. The molecular structure of monadelphin A, 2, consists of four six‐membered fused rings (A, B, C and D) and one five‐membered ring (E); they have twist‐boat (A and C), chair (B), screw‐boat (D) and planar (E) conformations. The molecule crystallizes in the space group P212121 with the contribution of many synthons usually found in compounds having the same moieties. However, the secondary alcohol–acetate O—H...OOC and secondary alcohol–ketone O—H...O=C synthons (occurrences of 16.7% each in these compounds) are missing. The furan–acetate Csp2—H...OOC synthon not observed in these compounds greatly contributes to the layered packing of 2. The layered packing is very close to those of 7‐oxogedunin (5) and 6‐dehydro‐7‐deacetoxy‐7‐oxogedunin (6), which both crystallize in the space group P21. [ABSTRACT FROM AUTHOR]

The title compound, C 13 H 10 BrNO 2 , was obtained by the reaction of 2,5-di-bromo-benzoic acid and aniline. The mol-ecule is twisted with a dihedral angle between the aromatic rings of 45.74 (11)° and an intr-amolecular N-H⋯O hydrogen bond is seen. In the crystal, pairwise O-H⋯O hydrogen bonds generate carb-oxy-lic acid inversion dimers., (© Kang and Long 2024.)

Three amino alcohols, 3-amino-1-propanol (abbreviated as 3a1pOH), 2-amino-1-butanol (2a1bOH), and 2-amino-2-methyl-1-propanol (2a2m1pOH), were reacted with quinoline-2-carboxylic acid, known as quinaldinic acid. This combination yielded three salts, (3a1pOHH)quin (1, 3a1pOHH+ = protonated 3-amino-1-propanol, quin− = anion of quinaldinic acid), (2a1bOHH)quin (2, 2a1bOHH+ = protonated 2-amino-1-butanol), and (2a2m1pOHH)quin (3, 2a2m1pOHH+ = protonated 2-amino-2-methyl-1-propanol). The 2-amino-1-butanol and 2-amino-2-methyl-1-propanol systems produced two polymorphs each, labeled 2a/2b and 3a/3b, respectively. The compounds were characterized by X-ray structure analysis on single-crystal. The crystal structures of all consisted of protonated amino alcohols with NH3+ moiety and quinaldinate anions with carboxylate moiety. The used amino alcohols contained one OH and one NH2 functional group, both prone to participate in hydrogen bonding. Therefore, similar connectivity patterns were expected. This proved to be true to some extent as all structures contained the NH3+∙∙∙−OOC heterosynthon. Nevertheless, different hydrogen bonding and π∙∙∙π stacking interactions were observed, leading to distinct connectivity motifs. The largest difference in hydrogen bonding occurred between polymorphs 3a and 3b, as they had only one heterosynton in common.

Di(1H‐indol‐3‐yl)methanes (DIMs) and their derivatives are one of the highly essential indole derivatives with a broad spectrum of biological activities. The scaffold involves two indole/substituted indole moieties connected to each other via a methenyl bridge generally at the 3,3' positions, as well as 2,2' and 2,3' positions. Synthesis of such moieties with the use of easily available chemicals and process is highly desirable for its tremendous importance in the fields of organic and medicinal chemistry. Herein, we review the synthesis of 3,3'‐methylene bridged indoles with the use of some methylene surrogates under various chemical and catalytic conditions. [ABSTRACT FROM AUTHOR]

Crystal shapes can be affected by different solvents from sheet, rod, to block because they can enter into the crystal lattice and co-crystallize with the ligands from various instantaneous microenvironments. In this study, two new supramolecular solvates, formulated as [(C8H4NO6+)·(C4H8N5−)]·H2O (1) and [(C8H3NO62+)·(C4H8N5−)2]·CH3OH (2), were synthesized by the combination of 2,4-diamino-6-methyl-1,3,5-triazine (DAMT) and 5-nitroisophthalic acid (H2NIPA) from the solvent mixture of CH3COCH3–H2O/CH3OH–H2O, respectively. Interestingly, the structures of these two solvates contain both classical hydrogen bond N–H⋯O and heterosynthon R 2 2 (8). And due to the different solutions, the supramolecular aggregates led to different crystal structures and shapes. Structural analysis shows that the differences in the two solvate structures mainly attributed to the unique hydrogen bonding pattern between the dimers and solvents molecules. 1 and 2 were characterized by single crystal X-ray diffraction, element analysis, infrared radiation, and thermogravimetric analysis. Two new supramolecular solvates were synthesized by the combination of 2,4-diamino-6-methyl-1,3,5-triazine (DAMT) and 5-nitroisophthalic acid (H2NIPA) from the solvent mixture of CH3COCH3–H2O/CH3OH–H2O. [ABSTRACT FROM AUTHOR]

One of the methods for achieving high values of refractive indices (n│ / n┴) in the nematic phase is the use of unsaturated hydrocarbon fragments C = C C≡C in 1,4‐polyphenylene systems. Tolanic and terminal acetylene fragments are widely used in liquid crystal molecules, which are practically used in liquid crystal compositions. Arylacetylenecarboxylic acids are useful building blocks for tolanic structure synthesis. In this article we present an alternative method of synthesis arylacetylenecarboxylic acids in a two‐phase system using PEG as a catalyst. [ABSTRACT FROM AUTHOR]

The reaction of the K4[{Re6Si8}(OH)a6]·8H2O rhenium cluster salt with pyrazine (Pz) in aqueous solutions of alkaline or alkaline earth salts at 4 °C or at room temperature leads to apical ligand exchange and to the formation of five new compounds: [trans-{Re6Si8}(Pz)a2(OH)a2(H2O)a2] (1), [cis-{Re6Si8}(Pz)a2(OH)a2(H2O)a2] (2), (NO3)[cis-{Re6Si8}(Pz)a2(OH)a(H2O)a3](Pz)·3H2O (3), [Mg(H2O)6]0.5[cis-{Re6Si8}(Pz)a2(OH)a3(H2O)a]·8.5H2O (4), and K[cis-{Re6Si8}(Pz)a2(OH)a3(H2O)a]·8H2O (5). Their crystal structures are built up from trans- or cis-[{Re6Si8}(Pz)a2(OH)a4−x(H2O)ax]x−2 cluster units. The cohesions of the 3D supramolecular frameworks are based on stacking and H bonding, as well as on H3O2−bridges in the cases of (1), (2), (4), and (5) compounds, while (3) is built from stacking and H bonding only. This evidences that the nature of the synthons governing the cluster unit assembly is dependent on the hydration rate of the unit.

Our recent investigations for the radiosynthesis of [18F]fluoromethyl tosylate have highlighted that choice of quaternary methyl ammonium (QMA) cartridge used during the radiosynthesis can significantly impact the radiochemical yields. Often the details of the QMA cartridge used in fluourine‐18 syntheses are not fully described. However, our studies demonstrate that the type, the size, and nature (method by which it has been conditioned) of the QMA cartridge used during the radiosynthesis can make a significant impact in the labelling efficiency. This paper investigates the use of three QMA cartridges and demonstrates that radiochemical yield (decay corrected) of [18F]fluoromethyl tosylate can increase from 46% to 60% by simply changing the QMA cartridge (and leaving all other reagents and labelling conditions exactly the same). These learnings may be applied to improve the radiochemical yields of a number of [18F]‐fluorinated tracers (and synthons), where the labelling step is base‐sensitive to increase the radiochemical yield, thereby significantly benefiting the radiochemistry and nuclear medicine community. This paper also highlights the necessity of the radiochemistry community to ensure the details of QMA cartridges used in fluorine‐18 chemistry are fully and accurately described, since this will improve the translation of radiochemical methods from one laboratory to another. Impact of 3 different QMA cartridges on the yields of [18F]fluoromethyl tosylate. [ABSTRACT FROM AUTHOR]

Halogen bonded lamellar motifs have been found in trinuclear crystals of ZnII–LnIII–ZnII coordination compounds. Although the coordination units have very similar skeletons, the crystal structures are built of halogen bonded dimers or trimers arranged in monoclinic or trigonal layers. The role of halogen bonding as stabilizing forces in building of long-range synthon aufbau modules (LSAM) is discussed. Halogen bonded lamellar supramolecular motifs have been found in the series of trinuclear crystals of ZnII–LnIII–ZnII complexes with N , N ′-bis(5-bromo-3-methoxysalicylidene)-1,3-diamino-2-propanol, with formulae [{Zn(HL)} 2 (μ -OAc) 2 Ln]NO 3 ·2CH 3 OH·2H 2 O (1 , 2) and [{Zn(HL)} 2 (μ -OAc) 2 Ln]NO 3 ·5.33H 2 O (3 , 4), where Ln = La (1), Ce (2), Er (3) and Yb (4). The isoskeletal crystals form monoclinic (1 , 2) or trigonal (3 , 4) layers built of halogen bonded dimers or trimers. The role of halogen bonding as a stabilizing force in building of long-range synthon aufbau modules (LSAM) is discussed. The heterotrinuclear coordination compounds were characterized by elemental analysis, FTIR and UV–Vis spectroscopy, thermal analysis, photoluminescence measurements, X-ray crystallography and Hirshfeld surface analyses. [ABSTRACT FROM AUTHOR]

Abstract Lamivudine (β-L-2′,3′-dideoxy-3′-thiacytidine, 3 TC), is one of the most investigated drugs in the fields of solid state chemistry and crystal engineering. Already in the year 1996, there was the first report of two crystal forms of lamivudine. Since then, more than 45 solid forms have been discovered, totaling 47 different arrangements of the same drug in the solid state (4 true polymorphs, 2 hydrates, 22 salts, 7 cocrystals, 5 cocrystals of salts, 6 so-called duplexes and 1 solid solution). Lamivudine has received much attention and there are numerous publications on its solid state forms, which have indeed brought important advances in our knowledge about solid state structure and improvement of pharmaceutical performance, but have also introduced challenges with respect to analysis and reproducibility. The purpose of this review is to describe all lamivudine solid forms currently known, focusing on their structural features. The description and occurrence of all 5'-CH 2 OH conformations, oxathiolane puckers and supramolecular synthons in all available lamivudine crystal forms is presented here. These structural information and characterization data will be useful for pharmaceutical design and analysis, as well as demonstrating the applicability of crystal engineering strategies to drugs with the same motifs as lamivudine. Graphical abstract Image 1062 Highlights • 47 different ways to load a same drug in the solid state. • 4 polymorphs, 2 hydrates, 22 salts, 7 cocrystals, 5 cocrystals of salts, 6 duplexes and 1 solid solution. • Description and occurrence of all 5'-CH 2 OH conformations, oxathiolane puckers and supramolecular synthons. • Finding lamivudine synthons in other drugs. • Joining structural and characterization data useful in pharmaceutical design and analysis. [ABSTRACT FROM AUTHOR]

Abstract To the best of our knowledge, the first co-crystallization of the pharmaceutical ingredient 4-aminoantipyrine is reported with 2-aminobenzoic acid as the co-former, and the method used for its supramolecular synthesis is discussed. Two molecular salts of 4-aminoantipyrine, as well as two co-crystals of a derivative of 4-aminoantipyrine were also synthesized. The complexes discussed show that careful application of synthon theory, choice of solvent and consideration of the p K a difference between 4-aminoantipyrine and the co-former are required to successfully co-crystallize this reactive molecule. In summary, the co-former must be chosen so that its functional group forms a robust heterosynthon with the reactive molecule. The presence of polar solvents or large p K a differences between 4-aminoantipyrine and its potential co-crystallizer favors salt formation, whereas a non-polar solvent and a small p K a difference is required for the co-crystallization of 4-aminoantipyrine. Graphical abstract Image [ABSTRACT FROM AUTHOR]