A three‐dimensional hydrogen‐bonded framework in (2S*,4R*)‐7‐fluoro‐2‐exo‐[(E)‐styryl]‐2,3,4,5‐tetrahydro‐1H‐1,4‐epoxy‐1‐benzazepine

Molecules of the title compound, C₁₈H₁₆FNO, are linked into a three‐dimensional framework structure by a combination of two C—H...O hydrogen bonds and three C—H...π(arene) hydrogen bonds. Comparisons are made with the (2R,4R) diastereoisomer and with the corresponding pair of diastereoisomeric 7‐chloro analogues.     

rac‐5‐Diphenylacetyl‐2,2,4‐trimethyl‐2,3,4,5‐tetrahydro‐1,5‐benzothiazepine and rac‐5‐formyl‐2,2,4‐trimethyl‐2,3,4,5‐tetrahydro‐1,5‐benzothiazepine

rac‐5‐Diphenylacetyl‐2,2,4‐trimethyl‐2,3,4,5‐tetrahydro‐1,5‐benzothiazepine, C₂₆H₂₇NOS, (I), and rac‐5‐formyl‐2,2,4‐trimethyl‐2,3,4,5‐tetrahydro‐1,5‐benzothiazepine, C₁₃H₁₇NOS, (II), are both characterized by a planar configuration around the heterocyclic N atom. In contrast with the chair conformation of the parent benzothiazepine, which has no substituents at the heterocyclic N atom, the seven‐membered ring adopts a boat conformation in (I) and a conformation intermediate between boat and twist‐boat in (II). The molecules lack a symmetry plane, indicating distortions from the perfect boat or twist‐boat conformations. The supramolecular architectures are significantly different, depending in (I) on C—H...O interactions and intermolecular S...S contacts, and in (II) on a single aromatic π–π stacking interaction.     

2‐[(E)‐(4‐Hydroxy‐3‐methoxybenzylidene)amino]‐N‐(2‐methylphenyl)‐4,5,6,7‐tetrahydro‐1‐benzothiophene‐3‐carboxamide

The title compound, C₂₄H₂₄N₂O₃S, exhibits antifungal and antibacterial properties. The compound crystallizes with two molecules in the asymmetric unit, with one molecule exhibiting `orientational disorder' in the crystal structure with respect to the cyclohexene ring. The o‐toluidine groups in both molecules are noncoplanar with the respective cyclohexene‐fused thiophene ring. In both molecules, there is an intramolecular N—H...N hydrogen bond forming a pseudo‐six‐membered ring which locks the molecular conformation and eliminates conformational flexibility. The crystal structure is stabilized by O—H...O hydrogen bonds; both molecules in the asymmetric unit form independent chains, each such chain consisting of alternating `ordered' and `disordered' molecules in the crystal lattice.     

Bulk free‐radical photopolymerizations of 1‐vinyl‐2‐pyrrolidinone and its derivatives

An investigation of the free‐radical bulk photopolymerization of 1‐vinyl‐2‐pyrrolidinone (NVP) with an NVP‐based crosslinker, 1,6‐(bis‐3‐vinyl‐2‐pyrrolidinonyl)hexane (BNVP), and an NVP‐based comonomer, 3‐hexyl‐1‐vinyl‐2‐pyrrolidinone (VHP), was carried out. The enthalpies of polymerization were determined for NVP and VHP to be 30.8 and 35.7 kJ/mol, respectively. The rates of polymerization were determined for NVP/VHP and NVP/BNVP systems at various temperatures. These photopolymerization studies revealed that the overall rates of polymerization of these 3‐alkylated‐2‐pyrrolidinone derivatives increased with substitution onto the pyrrolidinone ring. A series of pyrrolidinone‐based additives in bulk NVP were used in model photopolymerizations of NVP for the evaluation of plasticizer effects. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 694–706, 2002; DOI 10.1002/pola.10142     

Weak intermolecular interactions in 11‐chloro‐2,3,4,5‐tetrahydro‐1H‐cyclohepta[b]quinoline

The title compound, C₁₄H₁₄ClN, is a chloro analogue of tacrine, an acetylcholinesterase inhibitor. The compound comprises a seven‐membered alicyclic ring whose CH donor groups are engaged in extensive intermolecular interactions. The important feature of this crystal structure is that, regardless of the presence of two typical hydrogen‐bonding acceptors, viz. chlorine and nitrogen, the corresponding C—H...Cl and C—H...N interactions take no significant role in crystal stabilization. The molecules form dimers through π–π interactions with an interplanar distance between interacting pyridine rings of 3.576 (1) Å. Within the dimers, the molecules are additionally interconnected by four C—H...π interactions. The dimers arrange into regular columns via further intermolecular C—H...π interactions.     

The Torsional Barriers of 2‐Hydroxy‐ and 2‐Fluorobiphenyl: Small but Measurable

By making use of a novel diastereotopicity probe, namely C(CF₃)₂OH, it has been possible to measure by very low temperature ¹⁹F NMR spectroscopy the elusive aryl–aryl rotation barriers of biphenyls bearing an OH or F group in one ortho position. The experimental values (5.4 and 4.4 kcal mol^?1, respectively) are matched by those from ab initio calculations (5.3 and 4.3 kcal mol^?1, respectively).     

2β‐Hydroxy‐4′‐demethyldesoxy­podophyllotoxin

A room‐temperature single‐crystal X‐ray structure determination of the title compound, C₂₁H₂₀O₈, confirms the stereochemical assignment made previously on the basis of spectroscopic studies [Shaari & Waterman (1994). J. Nat. Prod. 57 , 720–724].     

2′‐Hydroxy‐4′′‐dimethylaminochalcone

The title compound, 3‐[4‐(di­methyl­amino)­phenyl]‐1‐(2‐hydroxy­phenyl)­prop‐2‐en‐1‐one, C₁₇H₁₇NO₂, is a chalcone derivative substituted by 2′‐hydroxyl and 4′′‐di­methyl­amino groups. The crystal structure indicates that the aniline and hydroxy­phenyl groups are nearly coplanar, with a dihedral angle of 10.32 (16)° between their phenyl rings. The molecular planarity of this substituted chalcone is strongly affected by the 2′‐hydroxyl group.     

New polyelectrolytes based on 4‐vinyl‐1,2,3‐triazole and 1‐vinylimidazole

Copolymers of 4‐vinyl‐1,2,3‐triazole and 1‐vinylimidazole (VI) were obtained by radical copolymerization of (4‐vinyl‐1H‐1,2,3‐triazol‐1‐yl)methyl pivalate with VI followed by alkali hydrolysis. Reactivity ratios of the triazole and imidazole monomers are 0.51 and 0.30, respectively. Theoretical quantum‐chemical calculations by the PM3 semiempirical method give close values, which show that the obtained reactivity ratios reflect the activity of the vinyl groups. Polyelectrolyte properties of the copolymers were studied by potentiometric titration. Hydrogen bonds between the protonated triazole cycle and the triazole or imidazole units were found to considerably influence the solubility and solution properties of the copolymers. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Four differently substituted 2‐aryl‐2,3,4,5‐tetrahydro‐1H‐1,4‐epoxy‐1‐benzazepines: hydrogen‐bonded structures in one,two and three dimensions

In (2RS,4SR)‐7‐chloro‐2‐exo‐(2‐chloro‐6‐fluorophenyl)‐2,3,4,5‐tetrahydro‐1H‐1,4‐epoxy‐1‐benzazepine, C₁₆H₁₂Cl₂FNO, (I), molecules are linked into chains by a single C—H...π(arene) hydrogen bond. (2RS,4SR)‐2‐exo‐(2‐Chloro‐6‐fluorophenyl)‐2,3,4,5‐tetrahydro‐1H‐1,4‐epoxy‐1‐benzazepine, C₁₆H₁₃ClFNO, (II), is isomorphous with compound (I) but not strictly isostructural with it, as the hydrogen‐bonded chains in (II) are linked into sheets by an aromatic π–π stacking interaction. The molecules of (2RS,4SR)‐7‐methyl‐2‐exo‐(4‐methylphenyl)‐2,3,4,5‐tetrahydro‐1H‐1,4‐epoxy‐1‐benzazepine, C₁₈H₁₉NO, (III), are linked into sheets by a combination of C—H...N and C—H...π(arene) hydrogen bonds. (2S,4R)‐2‐exo‐(2‐Chlorophenyl)‐2,3,4,5‐tetrahydro‐1H‐1,4‐epoxy‐1‐benzazepine, C₁₆H₁₄ClNO, (IV), crystallizes as a single enantiomer and the molecules are linked into a three‐dimensional framework structure by a combination of one C—H...O hydrogen bond and three C—H...π(arene) hydrogen bonds.     

4‐Hydroxy‐7‐methoxy‐2‐methyl‐5H‐1‐benzopyrano[4,3‐b]pyridin‐5‐one

The title compound, C₁₄H₁₁NO₄, consists of a methoxy‐substituted coumarin skeleton fused to a 2‐methyl‐4‐pyridone ring. The ring system of the mol­ecule is approximately planar and the methoxy group is roughly coplanar with the ring plane. The 4‐pyridone ring exists in a 4‐hydroxy tautomeric form and is stabilized by an intramolecular hydrogen bond between the O—H and C=O groups. Comparison of the results with those found for other structures containing the 4‐pyridone substructure reveals a substantial effect of the nature of the substituents bonded to the pyridine ring on the keto–enol tautomerism.     

Diastereoselective synthesis of substituted 2,3,4,5‐tetrahydro‐1H‐1‐benzazepine‐5‐carboxylic esters by a tandem reduction‐reductive animation reaction

An efficient, diastereoselective synthesis of substituted and unsubstituted 2,3,4,5‐tetrahydro‐1H‐1‐benzazepine‐5‐carboxylic esters has been developed based on the tandem reduction‐reductive amination reac tion. Catalytic hydrogenation of a series of 2‐(2‐nitrophenyl)‐5‐oxoalkanoic esters initiates a reaction sequence involving (1) reduction of the aromatic nitro group, (2) condensation of the N‐hydroxylamino (or amino) nitrogen with the side chain carbonyl, and (3) reduction of the seven‐membered cyclic imine. Cyclizations that produce 2‐alkyl‐2,3,4,5‐tetrahydro‐1H‐1‐benzazepine‐5‐carboxylic esters are diastereose lective for the product having the C2 alkyl and the C5 ester groups cis. In these reactions, the transannular ester group exerts a strong stereodirecting effect on the reduction of the cyclic imine intermediate, though not as strong as that observed in previous closures of 2‐alkyl‐1,2,3,4‐tetrahydroquinoline‐4‐carboxylic esters. This decrease in diastereoselectivity is attributed to (1) the greater distance between the ester and the imine double bond and (2) the increased conformational mobility of the larger ring, both of which diminish the stereodirecting effect of the ester. Finally, formation of the seven‐membered ring is sufficiently slow that reaction with the side chain ester group competes with heterocycle formation in several of the reactions.     

Synthesis of Acetyl and Iodo Derivatives of 4‐Hydroxy‐6‐phenyl‐6H‐pyrano[3,2‐c]pyridine‐2,5‐diones and 4‐Hydroxy‐1‐phenylpyridin‐2(1H)‐ones

A simple and efficient method has been described for the synthesis of acetyl and iodo derivatives of 4‐hydroxy‐6‐phenyl‐6H‐pyrano[3,2‐c ]pyridine‐2,5‐diones 1 and 4‐hydroxy‐1‐phenylpyridin‐2(1H )‐ones 5 . Compounds 1 with phenyl and alkyl substituent at C(7) and C(8), respectively, can be easily acetylated by refluxing in a mixture of acetic acid and polyphosphoric acid to give 3‐acetyl‐4‐hydroxy‐6‐phenyl‐6H‐pyrano[3,2‐c ]pyridine‐2,5‐diones 2 in excellent yields. Compounds 1 and 5 can be iodinated with iodine and anhydrous sodium carbonate in boiling dioxane to give 4‐hydroxy‐3‐iodo‐6‐phenyl‐6H‐pyrano[3,2‐c ]pyridine‐2,5‐diones 3 and 4‐hydroxy‐3‐iodo‐1‐phenylpyridin‐2(1H )‐ones 6 , respectively, in good yields. The structures were confirmed using infrared, nuclear magnetic resonance , and elemental analysis.     

(2RS,4SR)‐7‐Bromo‐2‐exo‐(2‐chlorophenyl)‐2,3,4,5‐tetrahydro‐1,4‐epoxynaphtho[1,2‐b]azepine: sheets built by the π‐stacking of hydrogen‐bonded chains

The molecules of the title compound, C₂₀H₁₅BrClNO, are linked into chains by a C—H...π(arene) hydrogen bond, in which the acceptor is the brominated ring of the naphthalene unit, and these chains are linked by an aromatic π–π stacking interaction, again involving the naphthalene unit, into a sheet structure.     

Alternative Synthesis of 2‐Hydroxy‐3,5,5‐trimethylcyclopent‐2‐en‐1‐one

The 2‐hydroxy‐3,5,5‐trimethylcyclopent‐2‐en‐1‐one ( 1 ) was synthesized in 42% yield by rearrangement of epoxy ketone 10 on treatment with BF₃⋅Et₂O under anhydrous conditions. Intermediate 10 was available from the known enone 8 , either via direct epoxidation (60% H₂O₂, NaOH, MeOH; yield 50%), or via reduction to the corresponding allylic alcohol 14 (LiAlH₄, THF), followed by epoxidation ([VO(acac)₂], ^tBuOOH) and reoxidation under Swern conditions, in 37% total yield.     

4‐Acetonyl­idene‐1‐ethyl‐2,3,4,5‐tetra­hydro‐1H‐1,5‐benzodiazepin‐2‐one

The title compound, C₁₄H₁₆N₂O₂, contains a diazepine ring, which appears in a boat conformation. An intramolecular hydrogen bond is formed between the NH group of the diazepine ring and a carbonyl O atom of one of the side chains.     

Collective Synthesis of 4‐Hydroxy‐2‐pyridone Alkaloids and Their Antiproliferation Activities

A collective synthesis of 4‐hydroxy‐2‐pyridone alkaloids—specifically, pretenellin B, prebassianin B, farinosone A, militarione D, pyridovericin, and torrubiellone C—has been achieved. Key steps include using a strategic convergent method to synthesize the densely substituted pyridone key intermediate by Suzuki–Miyaura cross‐coupling reaction, a divergent synthesis approach of target molecules by aldol condensation of pyridone intermediate with homologous aldehydes, and an iterative synthesis of homologous aldehydes with all‐trans‐polyene backbones. Interestingly, among the six tumor cell lines investigated, torrubiellone C was found to induce potent and apoptotic inhibitory activities on Jurkat T cells with IC₅₀ values of 7.05 μM . Hence, this approach could potentially contribute to the synthesis of bioactive small‐molecule libraries as well as drug discovery.     

Reactions with 4‐Hydroxy‐2‐methylbutananilides: Unexpected Formation of a Cyclopropanecarboxamide

The successive treatment of the N,N‐disubstituted 4‐hydroxy‐2‐methylbutanamide 2a with lithium diisopropylamide (LDA) and diphenyl phosphorochloridate (DPPCl) led to the 1‐methylcyclopropanecarboxamide 10 in good yield. This base‐catalyzed cyclization offers a new approach to cyclopropanecarboxamides. Under similar conditions, the N‐monosubstituted 4‐hydroxy‐2‐methylbutanamide 2b gave the 3‐methylpyrrolidin‐2‐one 11 . The structure of the cyclopropanecarboxamide 10 was established by X‐ray crystallography.     

A study on the ability of 2,5‐dihydro‐ and 2,3,4,5‐tetrahydro‐1h‐phosphole oxides,as well as 7‐phosphanorbornene 7‐oxide derivatives to undergo uv light‐mediated fragmentation‐related phosphinylation of methanol

Reactivity of the title P‐heterocycles ( 1‐14 ) in the photoinduced fragmentation‐related phosphinylation of methanol was found to be influenced by the extent of ring strain and the UV absorption at 254 nm. The 7‐phosphanorbornene oxides ( 7‐14 ) are universal precursors due to their ring strain, no matter if they are UV‐active or not at 254 nm. The easily available 2,5‐dihydro‐1H‐phosphole oxides can be applied only in case of 1‐phenyl substitution that enhances the absorption at 254 nm. The ring strain of representative P‐heterocycles ( 5‐8 ) was evaluated by HF/6‐31G* and B3LYP/6‐31+G* calculations. UV spectra of compounds 5‐8 were interpreted by ZINDO/S and MNDO‐d calculations. The new precursors ( 11‐14 ) made possible the extension of the phosphinylations.