Three isomeric forms of hydroxyphenyl‐2‐oxazoline: 2‐(2‐hydroxyphenyl)‐2‐oxazoline, 2‐(3‐hydroxyphenyl)‐2‐oxazoline and 2‐(4‐hydroxyphenyl)‐2‐oxazoline

Crystal structures are reported for three isomeric compounds, namely 2‐(2‐hydroxy­phenyl)‐2‐oxazoline, (I), 2‐(3‐hydroxy­phenyl)‐2‐oxazoline, (II), and 2‐(4‐hydroxy­phenyl)‐2‐oxazoline, (III), all C₉H₉NO₂ [systematic names: 2‐(4,5‐dihydro‐1,3‐oxazol‐2‐yl)phenol, (I), 3‐(4,5‐dihydro‐1,3‐oxazol‐2‐yl)phenol, (II), and 4‐(4,5‐dihydro‐1,3‐oxazol‐2‐yl)phenol, (III)]. In these compounds, the deviation from coplanarity of the oxazoline and benzene rings is dependent on the position of the hydroxy group on the benzene ring. The coplanar arrangement in (I) is stabilized by a strong intra­molecular O—H⋯N hydrogen bond. Surprisingly, the 2‐oxazoline ring in mol­ecule B of (II) adopts a ³T₄ (^C2T_C3) conformation, while the 2‐oxazoline ring in mol­ecule A, as well as that in (I) and (III), is nearly planar, as expected. Tetra­mers of mol­ecules of (II) are formed and they are bound together via weak C—H⋯N hydrogen bonds. In (III), strong inter­molecular O—H⋯N hydrogen bonds and weak intra­molecular C—H⋯O hydrogen bonds lead to the formation of an infinite chain of mol­ecules perpendicular to the b direction. This paper also reports a theoretical investigation of hydrogen bonds, based on density functional theory (DFT) employing periodic boundary conditions.     

Methyl 2‐acetamido‐2‐deoxy‐β‐d‐glucopyranoside dihydrate and methyl 2‐formamido‐2‐deoxy‐β‐d‐glucopyranoside

Methyl 2‐acetamido‐2‐deoxy‐β‐d ‐glucopyranoside (β‐GlcNAcOCH₃), (I), crystallizes from water as a dihydrate, C₉H₁₇NO₆·H₂O, containing two independent molecules [denoted (IA) and (IB)] in the asymmetric unit, whereas the crystal structure of methyl 2‐formamido‐2‐deoxy‐β‐d ‐glucopyranoside (β‐GlcNFmOCH₃), (II), C₈H₁₅NO₆, also obtained from water, is devoid of solvent water molecules. The two molecules of (I) assume distorted ⁴C₁ chair conformations. Values of ϕ for (IA) and (IB) indicate ring distortions towards B_C2,C5 and ^C3,O5B, respectively. By comparison, (II) shows considerably more ring distortion than molecules (IA) and (IB), despite the less bulky N‐acyl side chain. Distortion towards B_C2,C5 was observed for (II), similar to the findings for (IA). The amide bond conformation in each of (IA), (IB) and (II) is trans, and the conformation about the C—N bond is anti (C—H is approximately anti to N—H), although the conformation about the latter bond within this group varies by ∼16°. The conformation of the exocyclic hydroxymethyl group was found to be gt in each of (IA), (IB) and (II). Comparison of the X‐ray structures of (I) and (II) with those of other GlcNAc mono‐ and disaccharides shows that GlcNAc aldohexopyranosyl rings can be distorted over a wide range of geometries in the solid state.     

Synthesis and Reactivity of 2‐Pyrrolidino‐, 2‐N‐Methylpiperazino‐, 2‐Piperidino‐, and 2‐Morpholino‐1,3,4‐thiadiazines

A variety of 2‐pyrrolidino‐, 2‐N‐methylpiperazino‐, 2‐piperidino‐, and 2‐morpholino‐1,3,4‐thiadiazines were prepared by cyclocondensation of phenacyl halides with thiosemicarbazides. Heating of the products resulted in desulfurization and formation of pyrazoles. The rate of this process strongly depends on the substitution pattern of the 1,3,4‐thiadiazines.     

Facile Synthesis and Properties of 2‐λ5‐Phosphaquinolines and 2‐λ5‐Phosphaquinolin‐2‐ones

Treatment of 2‐ethynylanilines with P(OPh)₃ gives either 2,2‐diphenoxy‐2‐λ⁵‐phosphaquinolines or 2‐phenoxy‐2‐λ⁵‐phosphaquinolin‐2‐ones under transition‐metal‐free conditions. This reaction offers access to an underexplored heterocycle, which opens up the study of the fundamental nature of the N?P^V double bond and its potential for delocalization within a cyclic π‐electron system. This heterocycle can serve as a carbostyril mimic, with application as a bioisostere for pharmaceuticals based on the 2‐quinolinone scaffold. It also holds promise as a new fluorophore, since initial screening reveals quantum yields upwards of 40 %, Stokes shifts of 50–150 nm, and emission wavelengths of 380–540 nm. The phosphaquinolin‐2‐ones possess one of the strongest solution‐state dimerization constants for a D–A system (130 M ^?1) owing to the close proximity of a strong acceptor (P?O) and a strong donor (phosphonamidate N? H), which suggests that they might hold promise as new hydrogen‐bonding hosts for optoelectronic sensing.     

First synthesis of 2‐(2,4,4‐trimethyl‐3,4‐dihydro‐2H‐benzo[h]chromen‐2‐yl)‐1‐naphthol and 3‐(2,4,4‐trimethyl‐3,4‐dihydro‐2H‐benzo[g]chromen‐2‐yl)‐2‐naphthol from 1‐ and 2‐naphthol derivatives

Two new structurally isomeric, 2‐(2,4,4‐trimethyl‐3,4‐dihydro‐2H‐benzo[h]chromen‐2‐yl)‐1‐naphthol ( 1 ) and 3‐(2,4,4‐trimethyl‐3,4‐dihydro‐2H‐benzo[g]chromen‐2‐yl)‐2‐naphthol ( 3 ) have been synthesized from 2‐acetyl‐1‐naphthol and ethyl‐3‐hydroxy‐2‐naphthoate, respectively, involving Grignard reaction, dehydration of the corresponding tertiary alcohols, and hetero Diels–Alder dimerization. The two benzochromenes ( 1 and 3 ) have been fully characterized by IR, NMR, and HRESIMS data. Their structures are further supported by crystallography of their corresponding acetates ( 2 and 4 ). J. Heterocyclic Chem., (2011).     

Synthesis and properties of gradient copolymers based on 2‐phenyl‐2‐oxazoline and 2‐nonyl‐2‐oxazoline

In this study, the structure–property relationships for a series of statistical 2‐nonyl‐2‐oxazoline (NonOx) and 2‐phenyl‐2‐oxazoline (PhOx) copolymers were investigated for the first time. The copolymerization kinetics were studied and the reactivity ratios were calculated to be r_NonOx = 7.1 ± 1.4 and r_PhOx = 0.02 ± 0.1 revealing the formation of gradient copolymers. The synthesis of a systematical series of NonOx–PhOx copolymers is described, whereby the amount of NonOx was increased in steps of 10 mol %. The thermal and surface properties were investigated for this series of well‐defined copolymers. The thermal properties revealed a linear decrease in glass transition temperature for copolymers containing up to 39 wt % NonOx. Furthermore, the melting temperature of the copolymers containing 0 to 55 wt % PhOx linearly decreased most likely due to disturbance of the NonOx crystalline domains by incorporation of PhOx in the NonOx part of the copolymer. The surface energies of spincoated polymer films revealed a strong decrease in surface energy upon incorporation of NonOx in the copolymers due to strong phase separation between NonOx and PhOx allowing the NonOx chains to orient to the surface. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 6433–6440, 2009     

Synthesis of 9‐[2‐(2‐hydroxymethyl‐2‐methyl‐, ‐(2‐acetoxymethyl‐2‐methyl‐, ‐(2,2‐di(hydroxymethyl)‐, and ‐(2,2‐Di(acetoxymethyl)‐1,3‐dioxan‐5‐yl)ethyl] derivatives of guanine and 2‐aminopurine

Synthesis of 9‐[2‐(2‐hydroxymethyl‐2‐methyl‐, ‐(2‐acetoxymethyl‐2‐methyl‐, ‐(2,2‐di(hydroxymethyl)‐, and ‐(2,2‐di(acetoxymethyl)‐1,3‐dioxan‐5‐yl)ethyl] derivatives of guanine and 2‐aminopurine, 2–9 , has been accomplished in seven to eight step sequences from readily available 1‐(tert‐butyldiphenylsilyloxy)‐acetone, 1,3‐di(tert‐butyldiphenylsilyloxy)acetone, and the diol 10 . Formation of cyclic ketals 11 and 12 was carried out successfully under an acidic condition using a catalytic amount of methanesulfonic acid along with excess anhydrous copper(II) sulfate in toluene. Subsequent reactions of desilylation, acetylation, hydrogenolysis, and bromination afforded the key intermediates 19 and 20 , which were coupled with 2‐amino‐6‐chloropurine to produce the purine compounds 21 and 22 in good yields. Guanine derivatives 2–5 were obtained from 21 and 22 by hydrolysis and acetylation, while the dechlorination and hydrolysis of 21 and 22 yielded the 2‐aminopurine compounds 6–9 .     

2－脱氧－烟酰胺基－β－D－氨基葡萄糖的合成和表征

A new nicotinic acid derivative,2-deoxy-2-nicotinoylamido-β-D-glucopyranose, was synthesized with β-configuration exclusively. The structure and properties of the product were characterized by ^1H NMR, PT-IR, MS, DSC and polarimeter. The details of ^1H NMR spectrum and the mass spectrum proved that there are a great amount of hydrogen bonds in the product.     

(2E)‐N‐(2‐Iodo‐4,6‐dimethylphenyl)‐2‐methylbut‐2‐enamide

The title compound, C₁₄H₁₈INO, crystallizes as +sc/+sp/+sc 2‐iodoanilide molecules (and racemic opposites) and shows significant intermolecular I...O interactions in the solid state, forming dimeric pairs about centres of symmetry. Under asymmetric Heck conditions, the S enantiomer of the dihydroindol‐2‐one was obtained using (R)‐(+)‐2,2′‐bis(diphenylphosphino)‐1,1′‐binaphthyl [(R)‐BINAP], suggesting a mechanism that proceeds by oxidative addition to give the title (P) enantiomer of the compound and pro‐S coordination of the Re face of the alkene in a conformation similar to that defined crystallographically, except that rotation about the C—C bond of the butenyl group is required.     

4‐(2‐Hydroxyphenyl)‐2‐phenyl‐2,3‐dihydro‐1H‐1,5‐benzodiazepine and the 2‐(2,3‐dimethoxyphenyl)‐, 2‐(3,4‐dimethoxyphenyl)‐ and 2‐(2,5‐dimethoxyphenyl)‐substituted derivatives

The 1,5‐benzodiazepine ring system exhibits a puckered boat‐like conformation for all four title compounds [4‐(2‐hydroxyphenyl)‐2‐phenyl‐2,3‐dihydro‐1H‐1,5‐benzodiazepine, C₂₁H₁₈N₂O, (I), 2‐(2,3‐dimethoxyphenyl)‐4‐(2‐hydroxyphenyl)‐2,3‐dihydro‐1H‐1,5‐benzodiazepine, C₂₃H₂₂N₂O₃, (II), 2‐(3,4‐dimethoxyphenyl)‐4‐(2‐hydroxyphenyl)‐2,3‐dihydro‐1H‐1,5‐benzodiazepine, C₂₃H₂₂N₂O₃, (III), and 2‐(2,5‐dimethoxyphenyl)‐4‐(2‐hydroxyphenyl)‐2,3‐dihydro‐1H‐1,5‐benzodiazepine, C₂₃H₂₂N₂O₃, (IV)]. The stereochemical correlation of the two C₆ aromatic groups with respect to the benzodiazepine ring system is pseudo‐equatorial–equatorial for compounds (I) (the phenyl group), (II) (the 2,3‐dimethoxyphenyl group) and (III) (the 3,4‐dimethoxyphenyl group), while for (IV) (the 2,5‐dimethoxyphenyl group) the system is pseudo‐axial–equatorial. An intramolecular hydrogen bond between the hydroxyl OH group and a benzodiazepine N atom is present for all four compounds and defines a six‐membered ring, whose geometry is constant across the series. Although the molecular structures are similar, the supramolecular packing is different; compounds (I) and (IV) form chains, while (II) forms dimeric units and (III) displays a layered structure. The packing seems to depend on at least two factors: (i) the nature of the atoms defining the hydrogen bond and (ii) the number of intermolecular interactions of the types O—H...O, N—H...O, N—H...π(arene) or C—H...π(arene).     

Preparation of Protected β2‐ and β3‐Homocysteine, β2‐ and β3‐Homohistidine,and β2‐Homoserine for Solid‐Phase Syntheses

The Ser, Cys, and His side chains play decisive roles in the syntheses, structures, and functions of proteins and enzymes. For our structural and biomedical investigations of β‐peptides consisting of amino acids with proteinogenic side chains, we needed to have reliable preparative access to the title compounds. The two β³‐homoamino acid derivatives were obtained by Arndt–Eistert methodology from Boc‐His(Ts)‐OH and Fmoc‐Cys(PMB)‐OH (Schemes 2–4), with the side‐chain functional groups' reactivities requiring special precautions. The β²‐homoamino acids were prepared with the help of the chiral oxazolidinone auxiliary DIOZ by diastereoselective aldol additions of suitable Ti‐enolates to formaldehyde (generated in situ from trioxane) and subsequent functional‐group manipulations. These include OH→O^tBu etherification (for β²hSer; Schemes 5 and 6), OH→STrt replacement (for β²hCys; Scheme 7), and CH₂OH→CH₂N₃→CH₂NH₂ transformations (for β²hHis; Schemes 9–11). Including protection/deprotection/re‐protection reactions, it takes up to ten steps to obtain the enantiomerically pure target compounds from commercial precursors. Unsuccessful approaches, pitfalls, and optimization procedures are also discussed. The final products and the intermediate compounds are fully characterized by retention times (t_R), melting points, optical rotations, HPLC on chiral columns, IR, ¹H‐ and ¹³C‐NMR spectroscopy, mass spectrometry, elemental analyses, and (in some cases) by X‐ray crystal‐structure analysis.     

(E)‐2‐Methyl‐3‐(2‐methyl‐2‐nitro­vinyl)‐1H‐indole and (E)‐3‐(2‐methyl‐2‐nitro­vinyl)‐2‐phenyl‐1H‐indole

In the title compounds, C₁₂H₁₂N₂O₂, (I), and C₁₇H₁₄N₂O₂, (II), respectively, the indole rings are planar and the vinyl groups lie out of the indole planes, making dihedral angles of 33.48 (5) and 41.31 (8)°, respectively. In (II), the dihedral angle between the phenyl and indole ring planes is 32.06 (6)°. In both mol­ecules, the double bond connecting the methyl­nitro­vinyl group and the indole nucleus adopts an E configuration. Notwithstanding the differences in space group [C2/c for (I) and P2₁2₁2₁ for (II)], the mode of packing of compounds (I) and (II) is determined by similar inter­molecular N—H⋯O hydrogen‐bonding inter­actions, forming chains that run parallel to [101] in (I) and [001] in (II).     

Synthesis and antimicrobial activity of novel 2‐(aryl)‐3‐[5‐(2‐oxo‐2H‐3‐chromenyl)‐1,3‐oxazol‐2‐yl]‐1,3‐thiazolan‐4‐ones

A series of novel 2‐(aryl)‐3‐[5‐(2‐oxo‐2H‐3‐chromenyl)‐1,3‐oxazol‐2‐yl]‐1,3‐thiazolan‐4‐ones 4a , 4b , 4c , 4e , 4f , 4g , 4h , 4i , 4j have been synthesized and assayed for their antibacterial activity against Gram‐positive bacteria viz. Bacillus subtilis (ATCC 6633), Staphylococcus aureus (ATCC 6538p), Micrococcus luteus (IFC 12708), and Gram‐negative bacteria viz. Proteus vulgaris (ATCC 3851), Salmonella typhimurium (ATCC 14028), Escherichia coli (ATCC 25922), and also antifungal activity against Candida albicans (ATCC 10231), Aspergillus fumigatus (HIC 6094), Trichophyton rubrum (IFO 9185), and Trichophyton mentagrophytes (IFO 40996). Among the screened compounds, 4d , 4e , 4f , 4g , and 4j exhibited potent inhibitory activity compared with the standard drug at the tested concentrations. The results reveal that, the presence of difluorophenyl in 4f and pipernyl ring in 4j at 2‐position of thiazolidine‐4‐one ring show significant inhibitory activity. The other compounds also showed appreciable activity against the test bacteria and fungi and emerged as potential molecules for further development. J. Heterocyclic Chem., 2011.     

2‐(2‐Oxoimidazolidinyl)ethyl 2‐methyl­prop‐2‐enoate

In the crystal structure of the title compound, C₉H₁₄N₂O₃, the molecules are linked by N—H?O=C bonds into chains parallel to [001]. Large crystals are readily obtained, presumably because of the hydrogen bonds and an energetically stable conformation of the mol­ecule.     

Polymorphism of 3‐(5‐phenyl‐1,3,4‐oxadiazol‐2‐yl)‐ and 3‐[5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl]‐2H‐chromen‐2‐ones

This study of 3‐(5‐phenyl‐1,3,4‐oxadiazol‐2‐yl)‐2H‐chromen‐2‐one, C₁₇H₁₀N₂O₃, 1 , and 3‐[5‐(pyridin‐4‐yl)‐1,3,4‐oxadiazol‐2‐yl]‐2H‐chromen‐2‐one, C₁₆H₉N₃O₃, 2 , was performed on the assumption of the potential anticancer activity of the compounds. Three polymorphic structures for 1 and two polymorphic structures for 2 have been studied thoroughly. The strongest intermolecular interaction is stacking of the `head‐to‐head' type in all the studied crystals. The polymorphic structures of 1 differ with respect to the intermolecular interactions between stacked columns. Two of the polymorphs have a columnar or double columnar type of crystal organization, while the third polymorphic structure can be classified as columnar‐layered. The difference between the two structures of 2 is less pronounced. Both crystals can be considered as having very similar arrangements of neighbouring columns. The formation of polymorphic modifications is caused by a subtle balance of very weak intermolecular interactions and packing differences can be identified only using an analysis based on a study of the pairwise interaction energies.     

2‐[2‐(Pyrrolidin‐2‐yl)propan‐2‐yl]‐1H‐pyrrole and its amide derivative 1‐{2‐[2‐(1H‐pyrrol‐2‐yl)propan‐2‐yl]pyrrolidin‐1‐yl}ethanone

In the title compounds, C₁₁H₁₈N₂, (II), and C₁₃H₂₀N₂O, (III), the pyrrolidine rings have twist conformations. Compound (II) crystallizes with two independent molecules (A and B) in the asymmetric unit. The mean planes of the pyrrole and pyrrolidine rings are inclined to one another by 89.99 (11) and 89.35 (10)° in molecules A and B, respectively. In (III), the amide derivative of (II), the same dihedral angle is much smaller, at only 13.42 (10)°. In the crystal structure of (II), the individual molecules are linked via N—H...N hydrogen bonds to form inversion dimers, each with an R²₂(12) graph‐set motif. In the crystal structure of (III), the molecules are linked via N—H...O hydrogen bonds to form inversion dimers with an R²₂(16) graph‐set motif.     

Reaction of 6‐Methyl‐2‐Thiouracil and 6‐Phenyl‐2‐Thiouracil with Chloro‐β‐Dicarbonyl and Bromo‐β‐Dicarbonyl Compounds and Their Nitrile Analogs

Derivatives of 2‐methylidene‐1,3‐dihydropyrimidin‐4‐ones 2a , 2b , 2c , 2d , 2e , 2f , 2g were synthesized by interaction of 6‐methyl‐2‐thiouracil and 6‐phenyl‐2‐thiouracil 1a , 1b with some activated halogenides: diethyl bromomalonate, ethyl 2‐chloro‐3‐oxobutanoate, ethyl 2‐bromocyanoacetate, 2‐bromo‐5,5‐dimethylcyclohexan‐1,3‐dione, and bromomalononitrile. The boiling of 1a with ethyl 2‐bromocyanoacetate in mixture of ethanol and EtONa results in intramolecular cyclization and formation of thiazolo[3,2‐a]pyrimidin‐5‐one 3 . Interaction of 1a with 3‐chloropentane‐2,4‐dione and 2‐bromo‐1,3‐diphenylpropane‐1,3‐dione yielded corresponding S‐substituted thiopyrimidines 4a , 4b . In general, the products of 1b S‐alkylation are less prone to sulfur extrusion. Reaction of 1b with diethyl bromomalonate in the absence of EtONa stops at the S‐alkylation step, while in the presence of EtONa in ethanol or PPh₃ in dioxane 2‐(ethoxycarbonylmethyl)thio‐6‐phenyl‐1,3‐dihydropyrimidin‐4(1H)‐one 6 is formed exclusively. Molecular structure and crystal structure of 2‐(1,1‐diethoxycarbonylmethyliden)‐6‐methyl‐1,3‐dihydropyrimidin‐4(1H)‐one 2a are discussed.     

1‐(2‐Cyclohex‐2‐enylpropionyl)‐3‐methylurea, 2‐ethyl‐5‐methylhexanamide and 2‐ethylpentanamide: three products of barbiturate decomposition

The three title compounds were obtained by reactions which mimic, with more extreme conditions, the in vivo metabolism of barbiturates. 1‐(2‐Cyclohex‐2‐enylpropionyl)‐3‐methylurea, C₁₁H₁₈N₂O₂, (I), and 2‐ethylpentanamide, C₈H₁₇NO, (III), both crystallize with two unique molecules in the asymmetric unit; in the case of (III), one unique molecule exhibits whole‐molecule disorder. 2‐Ethyl‐5‐methylhexanamide, C₉H₁₉NO, (II), crystallizes as a fully ordered molecule with Z′ = 1. In the crystal structures, three different hydrogen‐bonding motifs are observed: in (I) a combination of R₂²(4) and R₂²(8) motifs, and in (II) and (III) a combination of R₄²(8) and R₂²(8) motifs. In all three structures, one‐dimensional ribbons are formed by N—H...O hydrogen‐bonding interactions.