Journal of Chemical Crystallography最新文献

{"title":"N,N-Dimethylbenzylamine as a Coformer for 3 Crystalline Organic Salts: Preparation, Spectral, Structural Investigation, Synthons Diversity and Hirshfeld Surface Analysis","authors":"Rui Gao,&nbsp;Shouwen Jin,&nbsp;Zhaozhi Li,&nbsp;Yuyan Yang,&nbsp;Liyang Shi,&nbsp;Daqi Wang","doi":"10.1007/s10870-025-01049-2","DOIUrl":"10.1007/s10870-025-01049-2","url":null,"abstract":"<div><p>In this work by means of the neutralization reaction of the N,N-dimethylbenzylamine, 3,5-dinitrobenzoic acid, 3,5-dinitrosalicylic acid and naphthalene-1,5-disulfonic acid, three bi- and tri-component crystalline salt systems are made by the gradual solvent volatilization method. The detailed features have been thoroughly conducted by the set of the analytical performances embracing the single crystal X-ray diffraction (SC-XRD), IR and EA, the melting points (m.p.s) were also measured. Their structural and supramolecular facets were analyzed in detail according to the noncovalent linkages and the supramolecular synthons. The role of the major intermolecular contacts was evaluated further by the Hirshfeld surface analysis (HSA) suite of programme for illucidating their importances. All the salts demonstrated the 3D net structures for the collective effect of the various non-covalent contacts. All contained the identical mol stoichiometry of 1:1 rate between the dmba &amp; the number of the acidic units and embraced the N–H···O &amp; O–H···O Hbonds together with the other non-covalent connections. Within all the salts, the respective residues are permanently tethered to each other via the energetic Hbonds belonging to the ionic N_{N,N-dimethylbenzylaminium}–O_acid fashion. Other extensive non-covalent connections of CH···O/CH₂···O/CH₃···O, C_π···π, CH···π/CH₃···π and π···π also function appreciable roles in the spatial expandings. The salts demonstrated the R₂²(4), R₂²(7), R₂²(12), R₂²(15), R₄³(11), R₄³(12), R₄⁴(20), R₄⁴(22), R₆⁵(30) and R₈⁸(44) rings. For the synergism of the traditional Hbonds and the diversified non-covalent connections, all applied the 3D appearances.</p><h3>Graphical Abstract</h3><p>The structures of the salts from dmba, 3,5-dinitrobenzoic acid, 3,5-dinitrosalicylic acid, and naphthalene-1,5-disulfonic acid are predominantly stabilized by the classical Hbonds together with the CH···O/CH₂···O/CH₃···O, C_π···π, CH···π/CH₃···π &amp; π···π associates, erecting the 3D graphs.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":615,"journal":{"name":"Journal of Chemical Crystallography","volume":"55 3","pages":"183 - 197"},"PeriodicalIF":0.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144990522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Monomeric Chromium Guanidinate– Synthesis and Structure","authors":"Sadaf Qayyum,&nbsp;Awal Noor","doi":"10.1007/s10870-025-01050-9","DOIUrl":"10.1007/s10870-025-01050-9","url":null,"abstract":"<div><p>Salt metathesis reaction between equimolar ratios of [Li{ArNC(NMe₂)Nar}(THF)] (Ar = C₆H₃Pr^<i>i</i>₂-2,6) and CrCl₃ in tetrahydrofuran (THF) leads to a mono(guanidiante) chromium(III) chloride complex, [Cr{ArNC(NMe₂)Nar}Cl₂(THF)₂]. X-ray analysis confirms it to be monomeric in solid state in which guanidinate ligand is coordinated in bidentate fashion to the six coordinated Cr center. The octahedral coordination is completed by two chloride atoms and two THF molecules. The herein reported compound is the first example of monomeric chromium halides of guanidinate ligands. Hirshfeld surface analyses indicate that H∙∙∙H interactions, H∙∙∙C/C∙∙∙H and H∙∙∙Cl/Cl∙∙∙H H–bonds are the three and at times the strongest contributions for the intermolecular interactions. The title compound, [C₃₅H₅₆Cl₂CrN₃O₂], crystallized in the monoclinic space group, <i>P</i>2₁/<i>n</i> with cell parameters: <i>a</i> = 11.5340(7) <i>b</i> = 17.6830(11) <i>c</i> = 18.0320(11) Å, <i>β</i> = 92.410(5), <i>V</i> = 3674.5(4) A³, Z = 4.</p></div>","PeriodicalId":615,"journal":{"name":"Journal of Chemical Crystallography","volume":"55 3","pages":"175 - 182"},"PeriodicalIF":0.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144990562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ice Ih Shaped Water Cluster in the Cage of an Ultramicroporous Metal-Organic Framework","authors":"Massimo Guelfi,&nbsp;Marco Taddei,&nbsp;Giulio Bresciani","doi":"10.1007/s10870-025-01048-3","DOIUrl":"10.1007/s10870-025-01048-3","url":null,"abstract":"<div><p>Reaction of 1,4-bis(1<i>H</i>-imidazol-1-yl)benzene ligand (bib) and CuSiF₆ in water/ dimethylsulfoxide (DMSO) as the solvent mixture affords purple crystals of a metal-organic framework, <b>1</b>, suitable for single crystal X-ray diffraction (SCXRD) analysis. <b>1</b> crystallizes in the triclinic <i>P</i> − 1 space group: <i>a</i> = 12.694(2) Å, <i>b</i> = 13.455(2) Å, <i>c</i> = 13.740(3) Å, <i>α</i> = 88.919(7)°, <i>β</i> = 67.864(7)°, <i>γ</i> = 65.029(6)°, <i>V</i> = 1942.9(6) ų. <b>1</b> was found to be a new phase of SIFSIX-23-Cu. Moreover, in the structure pores a cluster formed by two molecules of DMSO and ten molecules of water was identified possessing a double ice Ih-like shape.</p></div>","PeriodicalId":615,"journal":{"name":"Journal of Chemical Crystallography","volume":"55 3","pages":"198 - 205"},"PeriodicalIF":0.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144990521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crystal Structure of Anthracen-9-yl(3,6-dimethoxynaphthalen-2-yl)methanone: Decisive Factors for Formation of Two-Fold Helical Molecular Assemblies in Three Directions Affording Chiral Crystal","authors":"Kun Li,&nbsp;Hiroaki Iitsuka,&nbsp;Takehiro Tsumuki,&nbsp;Keiichi Noguchi,&nbsp;Noriyuki Yonezawa,&nbsp;Akiko Okamoto","doi":"10.1007/s10870-025-01041-w","DOIUrl":"10.1007/s10870-025-01041-w","url":null,"abstract":"<div><p>Anthracen-9-yl(3,6-dimethoxynaphthalen-2-yl)methanone (<b>III</b>), affords chiral crystals belonging to <i>P</i>2₁2₁2₁ space group. To investigate the decisive factors of chiral supramolecular crystallisation, the crystal structural characteristics of compound <b>III</b> were compared with the those of two 3-aroylated 2,7-dimethoxynaphthalene homologues, the 3-benzoylated (<b>I</b>) and 3-(1-naphthoylated) (<b>II</b>) derivatives, and those of their mother skeleton molecule, 2,7-dimethoxynaphthalene. The two homologues yielded achiral crystals in <i>P</i>2₁/c space group and the mother skeleton afforded chiral crystal in <i>P</i>2₁2₁2₁ space group. The spatial features of the single molecular structure, molecular accumulation, non-covalent bonding interactions, and proximity of molecules in crystal were analysed for the four compounds. In the crystalline single molecular structure of compound <b>III</b>, the connection between the 2,7-dimethoxynaphthalene ring and the ketonic carbonyl moiety is nearly coplanar and the anthracene ring connects to the ketonic carbonyl moiety almost perpendicularly. In the crystalline single molecular structures of homologues <b>I</b> and <b>II</b>, the 2,7-dimethoxynaphthalene rings are bonded with larger twists to the ketonic carbonyl groups than the arene rings. In crystal packings of homologues <b>I</b> and <b>II</b>, the centrosymmetric dimeric aggregations with pairs of complementary non-classical hydrogen bonds are observed. Compound <b>III</b> forms two-fold helical molecular assemblies with C–H…<i>π</i> non-classical hydrogen bonds along the <i>a</i>-axis. Hirshfeld surface analysis has emphasised that these packing motifs affect molecular packing distinctively. Compound <b>III</b> has the largest number of molecules in close proximity. The crystal structures of the four compounds, including non-aroylated 2,7-dimethoxynaphthalene, are interpreted in terms of their potential for chiral crystal formation by considering the transition in the types and ratios of effective non-classical hydrogen bonds functioning as inter- and intramolecular modes, under the primary influence of ketonic carbonyl group participating interactions.</p><h3>Graphical Abstract</h3><p>The crystal structures of the 3-(9-anthroylated) 2,7-dimethoxynaphthalene and its homologues having smaller sized-aromatic ring substituents, including non-aroylated 2,7-dimethoxynaphthalene, have been interpreted in terms of their potential for chiral crystal formation by considering the transition in the types and ratios of effective non-classical hydrogen bonds functioning as inter- and intramolecular modes.</p>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":615,"journal":{"name":"Journal of Chemical Crystallography","volume":"55 3","pages":"157 - 174"},"PeriodicalIF":0.6,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144990519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, Crystal Structure and Hirshfeld Surface Analysis of Bis(Benzene-1,2-Diamie)-Bis(2,4-Dihidroxybenzoato)-Nickel, [Ni(C6H8N2)2(C7H5O4)2]","authors":"Abdukadir Kh. Tashkulov,&nbsp;Khayit Kh. Turaev,&nbsp;Jamshid M. Ashurov,&nbsp;Ahatov Alisher Ashur o’g’li,&nbsp;Bekmurod A. Khurramovich,&nbsp;Aziz B. Ibragimov,&nbsp;Changkun Xia,&nbsp;Abul Monsur Showkot Hossain","doi":"10.1007/s10870-025-01046-5","DOIUrl":"10.1007/s10870-025-01046-5","url":null,"abstract":"<div><p>The title compound, [Ni(C₆H₈N₂)₂(C₇H₅O₄)₂] was obtained by dissolving of o-phenylenediamine (OPDA), nickel (II) sulfate and 2,4-dihydroxybenzoic acid (2,4-DHB) separately in 10 mL of ethanol (96%) and reacting with 10 mL of distilled water. The reaction mixture was stirred at room temperature and then slowly evaporated the pale green solution at 55–60 °C. The composition and crystal structure of the [Ni(C₆H₈N₂)₂(C₇H₅O₄)₂], complex was obtained at a constant temperature (30 ± 1 ºC) in 12 days. The complex is formed with two neutral bidentate OPDA ligands and two monodentate DHB ligands as [Ni(C₆H₈N₂)₂(C₇H₅O₄)₂]. The Ni atom is located at the inversion center, exhibiting a slightly octahedrally distorted coordination environment, with four nitrogen atoms of two o -phenylenediamine ligands (Ni–N) positioned in the equatorial plane and two oxygen atoms of 2,4-dihydroxybenzoic acid located in the axial plane. Here, two Ni–N bonds [Ni1 —N1 = 2.110(3), Ni1 —N1 ⁱ = 2.110(3) are exhibited the same bond length but opposite Ni–N bands are different Ni2 —N2 = 2.131(2), Ni2 —N2 ⁱ = 2.131(2)] and a longer axial two Ni—O bonds [2.136(2)]. The metal is located around the inversion center and is almost coplanar with the NiN₄ plane. In the crystal, inter-molecular hydrogen bonding interactions are observed at N1— H1..O1 and N2 — H2…O1 in the periodic network structure. The Hirshfeld surface analysis report indicates that the most important contributions to the crystal packing are H…H (44.6%), H….C/C….H (28.7%), O…H/H….O (23.7%), O…C/C….O (2.5%), C…C (1.7%), O…O(0.8%) interactions.</p><h3>Graphical Abstract</h3><p>The paper is designed by crystal structures of Ni(II) complex containing [Ni(C₆H₈N₂)₂(C₇H₅O₄)₂]. In continuation of our interest in the combination forms of benzene-1,2-diamine (ortho-phenylenediamine = OPDA) and 2,4-dihydroxybenzoic acid (2,4-DHB) with first-line conversion of metals, the authors considered a detailed discussion of the structure analysis of the Ni(II) complex from the mixed ligand of OPDA and 2,4-DHB using X-ray crystallographic technique</p>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":615,"journal":{"name":"Journal of Chemical Crystallography","volume":"55 2","pages":"147 - 155"},"PeriodicalIF":0.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutral Supramolecular Cluster-Based Nanorods from Direct Assembly of Three Building Units","authors":"JianJun Zhang,&nbsp;H. Andrew Zhou,&nbsp;Ted Grant,&nbsp;Abdessadek Lachgar","doi":"10.1007/s10870-025-01044-7","DOIUrl":"10.1007/s10870-025-01044-7","url":null,"abstract":"<div><p>The reaction between (Me₄N)₄[Nb₆Cl₁₂(CN)₆], [Mn(salen)Cl(H₂O)] (salen = N, N’-bis (salicylidene)ethylenedi-amine dianion), and <i>trans</i>-1,2-bis(4-pyridyl)-ethylene (bpe) led to the formation of {[Mn(salen)(H₂O)](bpe)[Mn(salen)]}₂[Nb₆Cl₁₂(CN)₆]⋅17H₂O (<b>1</b>). <b>1</b> features assemblies of 4.47 nm-long molecular nanorods in each of which two [Mn(salen)]⁺ connects <i>via</i> one bpe linker to form a dimeric unit and two dimeric units are <i>trans</i>-coordinated to one [Nb₆Cl₁₂(CN)₆]⁴⁻<i>via</i> cyanido. Its magnetic properties and thermal stability are also reported.</p><h3>Graphic Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div><div><p>Direct Assembly of {Nb₆} Cluster Units, [Mn(salen)]⁺, and Bpe Leads To Neutral Supramolecular Nanorods of 4.47 nm long</p></div></div></figure></div></div>","PeriodicalId":615,"journal":{"name":"Journal of Chemical Crystallography","volume":"55 2","pages":"140 - 146"},"PeriodicalIF":0.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crystallographic and Computational Studies of Semisynthesized 4-Allyl-2-Methoxyphenyl-4-Nitrobenzenesulfonate","authors":"Ayoub Ouaddi,&nbsp;Meriem Khedraoui,&nbsp;Bouchra Es-Sounni,&nbsp;Samir Chtita,&nbsp;Jean-Claude Daran,&nbsp;Ahmed Benharref,&nbsp;Moha Berraho,&nbsp;Lahcen El Ammari,&nbsp;Rabiaa Fdil,&nbsp;Mohamed Bakhouch","doi":"10.1007/s10870-025-01045-6","DOIUrl":"10.1007/s10870-025-01045-6","url":null,"abstract":"<div><p>This work is devoted to the semisynthesis of 4-allyl-2-methoxyphenyl-4-nitrobenzenesulfonate <b>3</b> from naturally occurring eugenol. The structure of the titled compound is established using IR, (¹H and ¹³C) NMR, and mass spectrometry. Single crystal X-ray diffraction is used to corroborate the structure of the compound <b>3</b>. Crystallographic study shows that compound <b>3</b> crystallizes in the monoclinic system with <i>P</i>2₁<i>/n</i> as the space group. DFT studies are carried out to calculate HOMO and LUMO energies. ADMET properties, Molecular docking and dynamic simulation studies are also performed towards the SARS-CoV-2 protein.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div><div><p>This paper describes a combined crystallographic and computational studies of the 4-allyl-2-methoxyphenyl-4-nitrobenzenesulfonate synthesized from naturally occurring eugenol</p></div></div></figure></div></div>","PeriodicalId":615,"journal":{"name":"Journal of Chemical Crystallography","volume":"55 2","pages":"127 - 139"},"PeriodicalIF":0.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, X-ray Structure, DFT, Hirshfeld Surface, QTAIM/RDG and Molecular Docking Analysis of 3-methyl-4-nitro-1,1-biphenyl (3-MNB)","authors":"Neha Kumari,&nbsp;Daljeet Singh,&nbsp;Archana Akaram Yadav,&nbsp;Sandeep Ashok Sankpal,&nbsp;Saminathan Murugavel,&nbsp;Duraiswamy Lakshmanan,&nbsp;Rajni Kant","doi":"10.1007/s10870-025-01043-8","DOIUrl":"10.1007/s10870-025-01043-8","url":null,"abstract":"<div><p>The synthesis of 3-methyl-4-nitro-1,1-biphenyl (3-MNB) and its crystal structure elucidated using experimental and theoretical methods has been reported in this paper. It crystallizes in the orthorhombic crystal system (space group P2₁2₁2₁) with unit cell parameters: a = 7.2918(4) Å, b = 12.0928(6) Å and c = 12.6759(7) Å and Z = 4. The structure has been characterized by FT-IR, NMR (¹H and ¹³C) and X-ray diffraction methods. There exists two C—H⋯O intermolecular hydrogen bond and two π…π interactions. Density functional theory (DFT/B3LYP/6-311 + + G(d, p)) has been employed for the optimization of the structure and the same was compared with the X-ray structure. The HOMO-LUMO energy gap and molecular electrostatic potential maps have been computed. The energy gap of 4.06 eV indicates that the molecule is stable and less reactive. Besides this, the molecular electrostatic potential (MEP) help determine the reactive sites of the molecule. The Hirshfeld surface analysis and 2-D fingerprint plots help explore the nature and percentage contribution of intermolecular interactions. The highest contribution to the total Hirshfeld surface area is from H…H contacts (47.2%) while the contribution of O…H/H…O contacts is 26.4%. The strength and nature of interactions present in the molecule have been characterized by RDG-based NCI and QTAIM analysis. DOS analysis has been performed to investigate the contribution of various orbitals. The molecular docking analysis analysis was performed to determine the binding patterns of 3-MNB with 1CX2, revealing a binding energy of -7.3 Kcal/mol, suggesting its potential as a COX-2 inhibitor.</p></div>","PeriodicalId":615,"journal":{"name":"Journal of Chemical Crystallography","volume":"55 2","pages":"115 - 126"},"PeriodicalIF":0.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Polymorphism and Whole-Molecule Disorder of an Antitubercular 8-Nitrobenzothiazinone","authors":"Rüdiger W. Seidel,&nbsp;Richard Goddard,&nbsp;Tom U. Schlegel,&nbsp;Adrian Richter,&nbsp;Ines Rudolph,&nbsp;Peter Imming","doi":"10.1007/s10870-025-01042-9","DOIUrl":"10.1007/s10870-025-01042-9","url":null,"abstract":"","PeriodicalId":615,"journal":{"name":"Journal of Chemical Crystallography","volume":"55 1","pages":"66 - 66"},"PeriodicalIF":0.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10870-025-01042-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143668068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ring-chain Tautomerism Trends in 3-(4’-alkyl-2’-oxobut-4’-yl)-4-hydroxycoumarins: Substituent Steric Bulk Controls Solution Composition and Equilibrium Thermodynamics of Alkyl Warfarin Analogs; Structural and Computational Analysis","authors":"Daniel A. Osborne,&nbsp;Jonathan O. Deridal,&nbsp;Jennifer Winarta,&nbsp;Margaret G. Batek,&nbsp;Sharalyn Sentinella,&nbsp;Edward J. Valente","doi":"10.1007/s10870-025-01040-x","DOIUrl":"10.1007/s10870-025-01040-x","url":null,"abstract":"&lt;div&gt;&lt;p&gt;As for warfarin, alkyl analogs of 3-(2’-oxo-4’-alkylbut-4’-yl)-4-hydroxycoumarins in solution display equilibria between &lt;i&gt;trans&lt;/i&gt; hemiketal ⇋ open, and open ⇋ &lt;i&gt;cis&lt;/i&gt; hemiketal tautomers. A steric trend is observed for the reactions by variable temperature NMR in CDCl&lt;sub&gt;3&lt;/sub&gt;, with ΔG (kJ/mol, 298 K) for &lt;i&gt;trans&lt;/i&gt; ⇋open, open ⇋ &lt;i&gt;cis&lt;/i&gt; and alkyl substituents: methyl (+ 0.3, -0.3), &lt;i&gt;n&lt;/i&gt;-pentyl (-2.6, + 3.0), isopropyl (-2.8, + 5.0), cyclohexyl (-4.3, + 7.2), neopentyl (-6.3, + 5.7) and &lt;i&gt;t&lt;/i&gt;-butyl (&lt;-13, &gt;+13) in CDCl&lt;sub&gt;3&lt;/sub&gt;. The &lt;i&gt;trans&lt;/i&gt; ⇋ open reactions typically are entropically favored but decreasingly enthalpically favored with substituent size. For the open ⇋ &lt;i&gt;cis&lt;/i&gt; reactions, enthalpic terms increasingly favor ring opening, while entropic contributions favoring open forms are moderated by greater conformational flexibility in the cyclic forms. Similar results were observed in d&lt;sub&gt;6&lt;/sub&gt;-dmso. In the solid state, (R)-3-(2’-oxopent-4’-yl)-4-hydroxycoumarin crystallizes in the monoclinic system (&lt;i&gt;P&lt;/i&gt; 2&lt;sub&gt;1&lt;/sub&gt;, Z = 6) with one &lt;i&gt;trans&lt;/i&gt; and two &lt;i&gt;cis&lt;/i&gt; hemiketal tautomers comprising the asymmetric unit. Racemic (±)-3-(2’-oxonon-4’-yl)-4-hydroxycoumarin crystallizes in the triclinic system (&lt;i&gt;P&lt;/i&gt; -1) as the &lt;i&gt;cis&lt;/i&gt; (2R,4R / 2 S,4 S) hemiketals. Though the alkyl warfarins typically crystallize as their cyclic hemiketals (&lt;i&gt;cis&lt;/i&gt; or &lt;i&gt;trans&lt;/i&gt;) even with substituents as bulky as neopentyl, the &lt;i&gt;t&lt;/i&gt;-butyl analog, racemic 3-(2’-oxo-5’,5’-dimethylhex-4’-yl)-4-hydroxycoumarin crystallizes in the monoclinic system (&lt;i&gt;P&lt;/i&gt; 2&lt;sub&gt;1&lt;/sub&gt;/&lt;i&gt;c&lt;/i&gt;) as the open coumarin tautomer, and its solutions also contain only the open form. These structures, augmented by literature determinations of alkyl warfarins and derivatives alkyl ketals, include (2 S,4 S)-&lt;i&gt;trans&lt;/i&gt;-2-ethoxy-2-methyl-3,4-dihydro-4-cyclohexyl-2 H,5 H-pyrano[3,2-c] (1)benzopyran-5-one (&lt;i&gt;P&lt;/i&gt; 2&lt;sub&gt;1&lt;/sub&gt;2&lt;sub&gt;1&lt;/sub&gt;2&lt;sub&gt;1&lt;/sub&gt;). From 23 determinations including six reported here, embedded dihydropyran ring conformations provide a structural basis for the steric interactions in the cyclic forms. Alkyl groups in &lt;i&gt;trans&lt;/i&gt; isomers distort the nearby coumarin carbonyl oxygen toward the opposite side of the coumarin ring. Computations (DFT) corroborate the relative stabilities of the cyclic hemiketals with the smaller substituents, but underestimate the importance of solvent on stabilization of the open tautomers. Sterimol analysis of the ΔΔGs for the open – cyclic reactions, relative to the methyl substituent, support a general steric model for the alkyl substituent-related changes in the tautomeric equilibria.&lt;/p&gt;&lt;h3&gt;Graphical Abstract&lt;/h3&gt;&lt;div&gt;&lt;figure&gt;&lt;div&gt;&lt;div&gt;&lt;picture&gt;&lt;img&gt;&lt;/picture&gt;&lt;/div&gt;&lt;div&gt;&lt;p&gt;As alkyl groups (substituted for the phenyl in warfarin) increase in bulk from methyl to &lt;i&gt;t&lt;/i&gt;-butyl, solutions increasingly favor the open tautomer over the cyclic hemiketals, and “&lt;i&gt;t&lt;/i&gt;-butyl warfar","PeriodicalId":615,"journal":{"name":"Journal of Chemical Crystallography","volume":"55 2","pages":"97 - 114"},"PeriodicalIF":0.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}