Cocrystals of 2,3,5,6‐tetrafluorobenzene‐1,4‐diol with diaza aromatic compounds

2,3,5,6‐Tetrafluorobenzene‐1,4‐diol easily forms cocrystals with heteroaromatic bases containing the pyrazine unit. In the 1:1 complexes with pyrazine, C₆H₂F₄O₂·C₄H₄N₂, (I), and quinoxaline, C₆H₂F₄O₂·C₈H₆N₂, (II), the crystal components are linked via O—H...N hydrogen bonds into one‐dimensional chains. With the largest base, phenazine, the 1:2 benzenediol–phenazine complex, C₆H₂F₄O₂·2C₁₂H₈N₂, (III), was obtained, with the molecules linked via O—H...N interactions into a discrete heterotrimer. In all three cocrystals, the two types of molecules are organized into layers via softer C—H...O and C—H...F interactions and π–π stacking interactions, with stronger hydrogen bonds linking molecules of adjacent layers. In (II) and (III), molecules are arranged into heterostacks, whereas in (I) separate stacks are formed by the heterocyclic base and the benzenediol molecule.     

Three 2,5‐dialkoxy‐1,4‐diethynylbenzene derivatives

2,5‐Diethoxy‐1,4‐bis[(trimethylsilyl)ethynyl]benzene, C₂₀H₃₀O₂Si₂, (I), constitutes one of the first structurally characterized examples of a family of compounds, viz. the 2,5‐dialkoxy‐1,4‐bis[(trimethylsilyl)ethynyl]benzene derivatives, used in the preparation of oligo(phenyleneethynylene)s via Pd/Cu‐catalysed cross‐coupling. 2,5‐Diethoxy‐1,4‐diethynylbenzene, C₁₄H₁₄O₂, (II), results from protodesilylation of (I). 1,4‐Diethynyl‐2,5‐bis(heptyloxy)benzene, C₂₄H₃₄O₂, (III), is a long alkyloxy chain analogue of (II). The molecules of compounds (I)–(III) are located on sites with crystallographic inversion symmetry. The large substituents either in the alkynyl group or in the benzene ring have a marked effect on the packing and intermolecular interactions of adjacent molecules. All the compounds exhibit weak intermolecular interactions that are only slightly shorter than the sum of the van der Waals radii of the interacting atoms. Compound (I) displays C—H...π interactions between the methylene H atoms and the acetylenic C atom. Compound (II) shows π–π interactions between the acetylenic C atoms, complemented by C—H...π interactions between the methyl H atoms and the acetylenic C atoms. Unlike (I) or (II), compound (III) has weak nonclassical hydrogen‐bond‐type interactions between the acetylenic H atoms and the ether O atoms.     

Synthesis of novel substituted pyridine derivatives from 3,5‐diacetyl‐2,6‐dimethylpyridine

A series of novel (1‐acetyl‐5‐aryl‐4,5‐dihydro)‐1H‐pyrazole substituted pyridine derivatives and poly substituted [2,3′‐bipyridine]‐5‐carbonitrile derivatives were synthesized from 3,5‐diacetyl‐2,6‐dimethylpyridine. The structures of two typical 3,5‐bis[1‐acetyl‐5‐(4‐chlorophenyl)‐4,5‐dihydro‐1H‐pyrazol‐3‐yl]‐2,6‐dimethylpyridines [ 3b(1) and 3b(2) ] were confirmed by X‐ray diffraction analysis. © 2009 Wiley Periodicals, Inc. Heteroatom Chem 20:123–130, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20522     

15N NMR of 1,4‐dihydropyridine derivatives

In this article, we describe the characteristic ¹⁵N and ¹H_N NMR chemical shifts and ¹J(¹⁵N–¹H) coupling constants of various symmetrically and unsymmetrically substituted 1,4‐dihydropyridine derivatives. The NMR chemical shifts and coupling constants are discussed in terms of their relationship to structural features such as character and position of the substituent in heterocycle, N‐alkyl substitution, nitrogen lone pair delocalization within the conjugated system, and steric effects. Copyright © 2013 John Wiley & Sons, Ltd.     

Cocrystals of 1,4‐diethynylbenzene with 1,3‐diacetylbenzene and benzene‐1,4‐dicarbaldehyde exhibiting strong nonconventional alkyne–carbonyl C—H…O hydrogen bonds between the components

Weak interactions between organic molecules are important in solid‐state structures where the sum of the weaker interactions support the overall three‐dimensional crystal structure. The sp‐C—H…N hydrogen‐bonding interaction is strong enough to promote the deliberate cocrystallization of a series of diynes with a series of dipyridines. It is also possible that a similar series of cocrystals could be formed between molecules containing a terminal alkyne and molecules which contain carbonyl O atoms as the potential hydrogen‐bond acceptor. I now report the crystal structure of two cocrystals that support this hypothesis. The 1:1 cocrystal of 1,4‐diethynylbenzene with 1,3‐diacetylbenzene, C₁₀H₆·C₁₀H₁₀O₂, (1), and the 1:1 cocrystal of 1,4‐diethynylbenzene with benzene‐1,4‐dicarbaldehyde, C₁₀H₆·C₈H₆O₂, (2), are presented. In both cocrystals, a strong nonconventional ethynyl–carbonyl sp‐C—H…O hydrogen bond is observed between the components. In cocrystal (1), the C—H…O hydrogen‐bond angle is 171.8 (16)° and the H…O and C…O hydrogen‐bond distances are 2.200 (19) and 3.139 (2) Å, respectively. In cocrystal (2), the C—H…O hydrogen‐bond angle is 172.5 (16)° and the H…O and C…O hydrogen‐bond distances are 2.25 (2) and 3.203 (2) Å, respectively.     

1,2,3‐Trimethoxy‐5,11‐dihydro­indolo[1,2‐b]isoquinoline‐5,11‐dione

The title compound, C₁₅H₁₉NO₅, crystallizes in the monoclinic space group P2₁/c with four mol­ecules in the asymmetric unit, which differ from each other in the orientation of their methoxy groups. Of the three methoxy groups in each molecule, one lies close to the plane of the mol­ecule and the other two have an out‐of‐plane conformation where they point in opposite directions. In the crystal structure, four different types of π‐stacks are observed and the mol­ecules pack in two different types of stacking sheets, with alternating mol­ecules A and B in one ribbon and alternating mol­ecules C and D in the other. The supramolecular structure is supported by C—H⋯O and π–π inter­actions.     

Synthesis of heterocyclic nitrogen derivatives from aryl‐1,4‐benzoquinones

Treatment of 2‐aryl‐3,6‐bis(arylamino)‐1,4‐benzoquinones 2a‐h with different acid chlorides, namely acetyl, phenylacetyl and chloroacetyl chloride yields 3a,7a‐dihydropyrrolo[2,3‐f]indole‐2,6‐dione 3, 5‐(N‐phenylacetylarylamino)‐3‐phenylindole‐2,6‐dione 4 and 3‐chloro‐5‐(N‐chloroacetylarylamino)indole‐2,6‐dione 5 respectively. Stirring 2‐aryl‐1,4‐benzoquinones ( 1 ) with ethylenediamine and/or o‐phenyl‐enediamine in methylene chloride gives pyrazino[2,3‐g]quinoxalines derivative 6 and/or tetrapentacene derivative 7 respectively. The products 5‐aryl‐ and 6‐aryl‐1/H‐indazole‐4,7‐diones 8 and 9 were obtained in the 1,3‐dipolar cycloaddition of diazomethane to ( 1 ).     

High yield synthesis of 4H‐1,4‐benzothiazine‐1,1‐dioxide derivatives

4H‐1,4‐Benzothiazine‐1,1‐dioxide derivatives were synthesized through a sequence of almost quantitative reactions. The commercial starting material 2‐(methylsulfanyl)aniline was Boc‐protected, N‐acylated and oxidized at the sulfur atom to obtain a sulfonyl derivative. An anionic transposition of the acyl group followed by asimultaneous deprotection‐cyclization gave the title products in excellent yields. All products and intermediates were fully characterized.     

Synthesis of new 4,5,6,7‐tetrahydro‐3H‐imidazo[4,5‐c]pyridine derivatives

The synthesis of new ligands for the H₃ histamine receptor is described. These new compounds are spinacine derivatives obtained by alkylation or Michael reaction at C6 position.     

2,5‐Dichloro‐2,5‐dihydro­thio­phene 1‐oxide: determinaton of the complete stereochemistry

The title five‐membered heterocycle, C₄H₄Cl₂OS, adopts an envelope conformation with the S atom at the tip of the flap. All three ring substituents, viz. the sulfoxide O atom and the two Cl atoms, are cis to each other. The two C atoms α to the sulfoxide group are also bonded to chlorine. The electron‐withdrawing chlorine substituents give rise to weak C—H·O hydrogen bonds with the sulfoxide O atom of a symmetry‐related mol­ecule [H·O = 2.44 (2) and 2.61 (2) Å, C·O = 3.143 (3) and 3.302 (2) Å and C—H·O = 129.9 (19) and 135.1 (19)°]. There is also a possible weak C—H·Cl inter­action. Chains of mol­ecules held together by these weak inter­actions run parallel to the a axis.     

Experimental and theoretical structural study of 2‐pyridyl‐ and 4‐hydroxyphenyl‐1,4‐dihydropyridine derivatives

A series of substituted 1,4‐dihydropyridines (1,4‐DHPs) has been synthesised following the well‐known Hantzsch's procedure for symmetrical 1,4‐DHP. The structures of these compounds have been thoroughly studied by X‐ray crystallographic analysis and semiempirical (AMI) calculations. A good agreement is found between the theoretical and experimental results. In all cases, the most stable conformation fulfils all the requirements needed for exhibiting an antagonist calcium effect.     

Two 1,4‐dihydropyridine derivatives with potential calcium‐channel antagonist activity

The title compounds, benzyl 4‐(3‐chloro‐2‐fluorophenyl)‐2‐methyl‐5‐oxo‐4,5,6,7‐tetrahydro‐1H‐cyclopenta[b]pyridine‐3‐carboxylate, C₂₃H₁₉ClFNO₃, (I), and 3‐pyridylmethyl 4‐[2‐fluoro‐3‐(trifluoromethyl)phenyl]‐2,6,6‐trimethyl‐5‐oxo‐1,4,5,6,7,8‐hexahydroquinoline‐3‐carboxylate, C₂₆H₂₄F₄N₂O₃, (II), belong to a class of 1,4‐dihydropyridines whose members sometimes display calcium modulatory properties. The 1,4‐dihydropyridine ring in each structure has a shallower than usual shallow‐boat conformation and is nearly planar in (I). In each structure, the halogen‐substituted benzene ring is oriented such that the halogen substituents are in a synperiplanar orientation with respect to the 1,4‐dihydropyridine ring plane. The oxocyclopentene ring in (I) is planar, while the oxocyclohexene ring in (II) has a half‐chair conformation, which is less commonly observed than the envelope conformation usually found in related compounds. In (I), the frequently observed intermolecular N—H...O hydrogen bond between the amine group and the carbonyl O atom of the oxocyclopentene ring of a neighbouring molecule links the molecules into extended chains; there are no other significant intermolecular interactions. By contrast, the amine group in (II) forms an N—H...N hydrogen bond with the pyridine ring N atom of a neighbouring molecule. Additional C—H...O interactions complete a two‐dimensional hydrogen‐bonded network. The halogen‐substituted benzene ring has a weak intramolecular π–π interaction with the pyridine ring. A stronger π–π interaction occurs between the 1,4‐dihydropyridine rings of centrosymmetrically related molecules.     

Synthesis and antimicrobial activity of some heterocyclic 2,6‐bis(substituted)‐1,3,4‐thiadiazolo‐, oxadiazolo‐, and oxathiazolidino‐pyridine derivatives from 2,6‐pyridine dicarboxylic acid dihydrazide

In this work, we report on the synthesis and preliminary biological activity screening of several heterocyclic derivatives 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 10a , 10b , 11 , 11a , 11b , 12 , 12a , 12b , 13 , 13a , 13b , 14 , 15 based on N2′,N6′‐diphenylthiosemi‐carbazide pyridine‐2,6‐dicarbohydrazide 2 , which has been obtained from the corresponding dihydrazide 1 . The biological screening showed that many of these compounds have good antimicrobial activities. The structure of the new compounds has been established on the bases of chemical and spectroscopic evidences. J. Heterocyclic Chem., (2011).     

One‐pot synthesis of pyridine derivatives via diels‐alder reactions of 2,4‐dimethyl‐5‐methoxyoxazole

A novel series of pyridine derivatives with anticipated biological activity have been synthesized via Diels‐Alder reactions of 2,4‐dimethyl‐5‐methoxyoxazole with different types of dienophiles. The regioselectivity of the cycloaddition was inverted from methylacrylate to tert‐butylacrylate. The structural elucidation of the new compounds was carried on the basis of spectral and X‐ray analyses. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:49–55, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20064     

Synthesis of new 3,3′‐(1,4‐phenylene)bis(1,5‐diones) derivatives

Several 3,3′‐(1,4‐phenylene)bis(1,5‐diones) and their chalcone precursors have been prepared in good to excellent yield via aldol addition and Michael addition starting from 3‐acetyl‐2,5‐dimethylfuran or 3‐acetyl‐2,5‐dimethyl‐thiophene with terephthalaldehyde in the presence of appropriate base NaOH or lithium diisopropylamide. The kind and amount of alkali played a critical role in improving the reaction rates and yields of the products. J. Heterocyclic Chem., (2011).     

1,4‐Dioxo‐1,4‐dihydronaphthalene‐2,3‐dicarbonitrile and 1,1,2,2‐Tetracyanoethene in Heterocyclization

This survey is mainly concerned with selected reactions of 1,4‐dioxo‐1,4‐dihydronaphthalene‐2,3‐dicarbonitrile and 1,1,2,2‐tetracyanoethene, which have use or potential use in heterocyclic synthesis.     

Synthesis and antifungal activity of spiro[cyclopropane‐1,4′‐pyrazol‐3‐one] derivatives

A series of new spiro[cyclopropane‐1,4′‐pyrazol‐3‐one] derivatives 3a‐h were synthesized by the reaction of 4‐arylidene‐3H‐pyrazol‐3‐one 1 with secondary and tertiary carbanions derived from a methylene and methine group bearing both a leaving group and electron‐withdrawing group, e.g. methyl chloroacetate, ethyl chloroacetate, isopropyl chloroacetate, tert‐butyl chloroacetate, chloroacetonitrile, 2‐chloro‐N,N‐diethylacetamide, methyl 2‐chloropropionate and 2‐chloropropionitrile, in the presence of sodium hydride. All the synthesized compounds 3a‐h were active against Candida albicans with MIC ≤ 25 μg/mL in vitro.     

(±)‐1‐Methyl‐1,3,6‐triphenyl‐7‐(2‐phenyl­propen­yl)‐1,2‐dihydro­naphthalene

The crystal structure of the title compound, C₃₈H₃₂, presents a novel framework that combines the functionalities of a 1,6‐diarene‐substituted 1,2‐dihydro­naphthalene (DHN) with a 1,4‐distyrylbenzene (DSB) to form a crossed bis‐diarene. The lamellar crystal structure is held together by arene–arene inter­actions. While the orientations of the phenyl rings of the DSB units alternate within both the R and the S substructures, the homochiral substructures feature opposing polarity along the long axes of the DHN‐based diarenes.     

4‐Anilino‐3‐nitro­pyridine

The structure of the title compound, C₂₂H₁₈N₆O₄, (I), comprises two unique mol­ecules that separately form hydrogen‐bonded polymer chains via N—H?N interactions. Molecular independence arises due to a difference in the dihedral angles between the linked rings, i.e. 52.19 (4) and 46.17 (5)°.