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.     

A Novel Route to α,ω‐Bis(acrylamidopeptide)‐Terminated Oligo(ethylene oxide) and Hydrogels

A new family of α,ω‐bis(acrylamidopeptide)‐terminated macromonomers were prepared via the ring‐opening addition of 4,4‐dimethyl‐2‐vinyl‐ and 2‐isopropenyl‐4,4‐dimethyl‐oxazol‐5‐on to α,ω‐diamine‐terminated poly(ethylene oxide). These macromonomers were used to produce hydrogels by means of thermally induced free‐radical polymerization. Swelling behavior and mechanical properties of the resulting hydrogels were influenced by the macromonomer type and the crosslinking density, as reflected by the equilibrium water uptake.     

Efficient Synthesis of 2‐(2‐Aminophenyl)‐2,3‐dihydropyridin‐4(1H)‐ones Based on a Cyclization/Ring Cleavage Procedure

(Benzyloxycarbonyl)‐protected 3,4‐benzo‐7‐hydroxy‐2,9‐diazabicyclo[3.3.1]non‐7‐enes were prepared by one‐pot cyclizations of 1,3‐bis(silyl enol ethers) with quinazolines. Subsequent hydrogenation resulted in one‐pot deprotection and rearrangement to give 2‐(2‐aminophenyl)‐2,3‐dihydropyridin‐4(1H)‐ones.     

Theoretical study of enantiomeric and geometric control in chiral guanidine‐catalyzed asymmetric 1,4‐addition of 5H‐oxazol‐4‐ones

Density functional theory calculations are used to study the reaction mechanism and origins of high stereoselectivity in chiral guanidine‐catalyzed asymmetric 1,4‐addition of 5H‐oxazol‐4‐ones. The reaction involves proton abstraction of 5H‐oxazol‐4‐one, C—C bond formation, and proton transfer. N1 atom of chiral guanidine exchanges its character as base and acid to activate 5H‐oxazol‐4‐one and to facilitate the product formation. The role of N2—H2 is not only H‐bond donor for 5H‐oxazol‐4‐one but also electron accepter for N1. The enantioselectivity related with rate‐limiting step 1 and Z/E selectivity determined in step 2 are primarily influenced by a five to six‐membered ring link in the backbone of chiral guanidine. The reaction proceeds along the favorable path with smaller rotations of the linked bonds. The enantioselectivity is improved with guanidine involving an electron‐deficient and bulky substituent. With methyl ether‐protected hydroxy in structure, the catalytic ability and enantioselective control of guanidine are extraordinarily low, affording the opposite enantiomer as major product. Z‐isomers are preferred in all cases. © 2013 Wiley Periodicals, Inc.     

(4S,5S)‐(+)‐4‐Hydro­xy­methyl‐2,5‐di­phenyl­oxazoline

The absolute configuration of the title compound, alter­natively called (+)‐(4,5‐di­hydro‐2,5‐di­phenyl­oxazol‐4‐yl)­methanol, C₁₆H₁₅NO₂, has been confirmed as 4S,5S. The hydroxy­methyl group and phenyl ring at the asymmetric C atoms exhibit β and α orientations, respectively. The exocyclic C—C bonds at the asymmetric C atoms are mutually anticlinal (?ac). The hydroxyl group and the N atom of the oxazoline ring are involved in an intermolecular hydrogen bond leading to chains of mol­ecules.     

Reaction of γ‐Hydroxy‐N‐[1‐(dimethylcarbamoyl)ethyl]butanamides under the ‘Direct Amide Cyclization’ Conditions

The preparation of the title compounds was achieved via the ‘azirine/oxazolone method’ starting from the corresponding γ‐hydroxy acids. Upon subjecting the γ‐hydroxy‐N‐[1‐(dimethylcarbamoyl)ethyl]butanamides 4 to the so‐called ‘direct amide cyclization’ (DAC) conditions, chlorinated acids 11 or imino lactones 12 were obtained as the sole products instead of the expected cyclodepsipeptides A or their cyclodimers (Scheme 4). Variation of the substituents in 4 did not affect the outcome of the reaction and a mechanism for the formation of both products from the intermediate oxazolone 13 has been proposed. Under the acidic conditions of the DAC, the imino lactones are formed as their HCl salts 12 , which, in polar solvents or on silica gel, reacted further to give the chlorinated acids 11 . Stabilization of the imino lactones was achieved by increasing the substitution in the five‐membered ring, and their structure, in the form of the hydrochlorides, was established independently by X‐ray crystallography (Fig. 4). A derivative 15 of the imino lactone 12a was prepared by the reaction with the 2H‐azirin‐3‐amine 10a ; its structure was also established by an X‐ray crystal‐structure determination (Fig. 3). Furthermore, the structures of the ω‐chloro acids 11a and 11b were determined by X‐ray crystallography (Fig. 2).     

一种经(E)-α-碘代烯基砜的钯催化交叉偶联反应立体选择合成(1Z,3E)-2-芳砜基取代的1,3-二烯的新方法

（E）-α-Stannylvinyl phenyl（or p-tolyl）sulfones underwent an iododestannylation reaction to afford （E）-α-iodovinyl phenyl（or p-tolyl）sulfones 1, which reacted with （E）-alkenylzirconium（IV） complexes 2 produced in situ by hydrozirconation of terminal alkynes in the presence of a Pd（PPh3）4 catalyst to afford stereoselectively （1Z,3E）-2- phenyl（or p-tolyl）sulfonyl-substituted 1,3-dienes 3 in good yields.     

Unexpected Spiroproducts from the Reaction of N‐Benzoylglycine with Ortho‐Formylbenzoic Acids −3,5′‐Dioxo‐2′‐Phenyl‐1,3‐Dihydrospiro[Indene‐2,4′‐[1,3]Oxazol]‐1‐yl Acetates: Establishments of Their Structure

This paper describes a method of preparation of new 3,5′‐dioxo‐2′‐phenyl‐1,3‐dihydrospiro[indene‐2,4′‐[1,3]oxazol]‐1‐yl acetate and its 5‐chloro‐ and bromoderivatives as products of interaction of N‐benzoylglycine (hippuric acid) with corresponding ortho‐formylbenzoic acids. The reaction carried out in acetic anhydride media in the presence of piperidine as catalyst. The novel spirocompounds were purified by column chromatography from multicomponent reaction mixtures. The composition of the spiro‐products was confirmed by C, H, N element analysis. The structure was established by IR, MS, ¹H‐ and ¹³C‐NMR analysis including COSY ¹H‐¹³C experiments.     

Synthesis of the 2‐Alkenyl‐4‐alkylidenebut‐2‐eno‐4‐lactone (=α‐Alkenyl‐γ‐alkylidenebutenolide) Core Structure of the Carotenoid Pyrrhoxanthin via the Regioselective Dihydroxylation of Hepta‐2,4‐diene‐5‐ynoic Acid Esters

A new strategy for the stereoselective synthesis of 4‐alkylidenebut‐2‐eno‐4‐lactones (=γ‐alkylidenebutenolides) with (Z)‐configuration of the exocyclic CC bond at C(4) was developed. It is exemplified by the synthesis of 4‐alkylidenebutenolactone 31 (Scheme 4), which constitutes a substructure of the carotenoids pyrrhoxanthin ( 1 ) and peridinin. The formation of the precursor 4‐(1‐hydroxyalkyl)butenolactone 29 was accomplished either by cyclocarbonylation of the prop‐2‐yn‐1‐ol moiety of 27 (→ 29 ) or by hydrostannylation of the isopropylidene‐protected alkynoic acid ester 26 (→ 28 ) followed by transacetalization/transesterification (→ 30 ). The 4‐alkylidenebutenolactone was formed by the anti‐selective Mitsunobu dehydration 29 → 31 .     

Synthesis of (4Z)‐4‐(Arylmethylidene)‐5‐ethoxy‐1,3‐oxazolidine‐2‐thiones by the Reaction of Ethyl (2Z)‐3‐Aryl‐2‐isothiocyanatoprop‐2‐enoates with Organolithium Compounds

A convenient one‐pot method for the preparation of (4Z)‐4‐(arylmethylidene)‐5‐ethoxy‐1,3‐oxazolidine‐2‐thiones 2 and 3 from ethyl (2Z)‐3‐aryl‐2‐isothiocyanatoprop‐2‐enoates 1 , which can be easily prepared from ethyl 2‐azidoacetate and aromatic aldehydes, has been developed. Thus, these α‐isothiocyanato α,β‐unsaturated esters were treated with organolithium compounds, including lithium enolates of acetates, to provide 5‐substituted (4Z)‐4‐(arylmethylidene)‐5‐ethoxy‐1,3‐oxazolidine‐2‐thiones, 2 , and 2‐[(4Z)‐(4‐arylmethylidene)‐5‐ethoxy‐2‐thioxo‐1,3‐oxazolidin‐5‐yl]acetates, 3 .     

Generation and reactivity of 3‐carbethoxy‐5‐phenyl‐5H,7H‐thiazolo[3,4‐c]oxazol‐4‐ium‐1‐olate

3‐Carbethoxy‐5‐phenyl‐5H,7H‐thiazolo[3,4‐c]oxazol‐4‐ium‐1‐olate was generated from (2R,4R)‐N‐ethoxyoxalyl‐2‐phenylthiazolidine‐4‐carboxylic acid and its reactivity studied. This münchnone showed low reactivity as dipole although from the reaction with dimethyl acetylenedicarboxylate the corresponding (3R)‐3‐phenyl‐17H,3H‐pyrrolo[1,2‐c]thiazole‐5,6,7‐tricarboxylate could be isolated. The thermolysis of (2R,4R)‐N‐ethoxyoxalyl‐2‐phenylthiazolidine‐4‐carboxylic acid in refluxing acetic anhydride led to the synthesis of N‐(1‐ethoxycarbonyl‐2‐phenylvinyl)‐2‐phenyl‐4‐thioxo‐1,3‐thiazolidine. The structure of methyl (2R,4R)‐N‐ethoxyoxalyl‐2‐phenylthiazoliddine‐4‐carboxylate was determined by X‐ray crystallography.     

3‐Benzyl‐2‐(4‐fluorophenyl)‐1,3‐thiazolidin‐4‐one

The title compound, C₁₆H₁₄FNOS, crystallizes with Z′ = 2 in the space group P2₁/c. In one of the two independent molecules, the heterocyclic ring is effectively planar, but in the other molecule this ring adopts an envelope conformation. The molecules are weakly linked by two C—H...O hydrogen bonds to form C₂²(14) chains. Comparisons are made with some symmetrically substituted 2‐aryl‐3‐benzyl‐1,3‐thiazolidin‐4‐ones.     

New TRANS/CIS tetrahydroisoquinolines. 3. [1,3]‐oxazolo‐[3,2‐B]‐tetrahydroisoquinolinones having an angular aryl substituent

The parent compound 5‐oxo‐10a‐phenyl‐2,3,10,10a‐tetrahydro‐5H‐[1,3]‐oxazolo‐[3,2‐b]‐isoquinoline‐10‐carboxylic acid ( 5 ) was prepared in large scale and a good yield by reaction between homophthalic anhydride ( 3 ) and 4,5‐dihydro‐2‐phenyl‐1,3‐oxazole ( 4 ). Thus, the closure of the isoquinoline ring and fusion of the 1,3‐oxazol ring occur in one step. Trans configuration was assumed for the product. The parent acid 5 was converted in four steps to the target aminomethyl derivatives 9a‐1 . The latter contain four features that make them interesting from pharmaceutical point of view.     

A new synthesis of cytotoxic ( )-7-epi-Goniofufurone

Cytotoxic styryl lactone, ( )-7-epi-Gonioftifurone (1), has been prepared with a new route from 3-O-benzyl-1,2-O-iso-propylidene-5-C-phenyl-β-L-ido-pentofuranose (6), a derivative of ( )-glucose. Treatment of 14 with HCl solution cleaved TBDMS and isopropylidene and simultaneously caused ring closure to afford 1 while treatment of 14 with Sc(OTf)3 only removed TBDMS to give 15.     

Synthesis of 1,3‐Dihydro‐3‐oxo‐2‐benzofuran‐1‐carboxylates via Intramolecular Cyclization of 2‐[2‐(Dimethoxymethyl)phenyl]‐ 2‐hydroxyalkanoates Followed by Oxidation

A novel and efficient method for the preparation of 1,3‐dihydro‐3‐oxo‐2‐benzofuran‐1‐carboxylates 4 under mild conditions has been developed. Thus, the reaction of [2‐(dimethoxymethyl)phenyl]lithiums, generated easily from 1‐bromo‐2‐(dimethoxymethyl)benzenes 1 , with α‐keto esters gives the corresponding 2‐[2‐(dimethoxymethyl)phenyl]‐2‐hydroxyalkanoates 2 . The TsOH‐catalyzed cyclization of these hydroxy acetals is followed by the oxidation of the resulting cyclic acetals 3 with PCC to give the desired products in satisfactory yields. The reaction of [2‐(dimethoxymethyl)‐4,5‐dimethoxyphenyl]lithium with (MeOC?O)₂, followed by treatment with NaBH₄ or organolithiums, affords 2‐[2‐(dimethoxymethyl)‐4,5‐dimethoxyphenyl]‐2‐hydroxyalkanoates 6 , which can similarly be transformed into the corresponding 1,3‐dihydro‐3‐oxo‐2‐benzofuran‐1‐carboxylates 7 in reasonable yields.     

New Approaches to the Synthesis of 4‐(2‐Aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones and 3‐Ureidoindoles and a Study of Their Interconversion

3‐Alkyl/aryl‐3‐ureido‐1H,3H‐quinoline‐2,4‐diones ( 2 ) and 3a‐alkyl/aryl‐9b‐hydroxy‐3,3a,5,9b‐tetrahydro‐1H‐imidazo[4,5‐c]quinoline‐2,4‐diones ( 3 ) react in boiling concentrated HCl to give 5‐alkyl/aryl‐4‐(2‐aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones ( 6 ). The same compounds were prepared by the same procedure from 2‐alkyl/aryl‐3‐ureido‐1H‐indoles ( 4 ), which were obtained from the reaction of 3‐alkyl/aryl‐3‐aminoquinoline‐2,4(1H,3H)‐diones ( 1 ) with 1,3‐diphenylurea or by the transformation of 3a‐alkyl/aryl‐9b‐hydroxy‐3,3a,5,9b‐tetrahydro‐1H‐imidazo[4,5‐c]quinoline‐2,4‐diones ( 3 ) and 5‐alkyl/aryl‐4‐(2‐aminophenyl)‐1,3‐dihydro‐2H‐imidazol‐2‐ones ( 6 ) in boiling AcOH. The latter were converted into 1,3‐bis[2‐(2‐oxo‐2,3‐dihydro‐1H‐imidazol‐4‐yl)phenyl]ureas ( 5 ) by treatment with triphosgene. All compounds were characterized by ¹H‐ and ¹³C‐NMR and IR spectroscopy, as well as atmospheric pressure chemical‐ionisation mass spectra.     

Cyclization vs. Elimination Reactions of 5‐Aryl‐5‐hydroxy 1,3‐Diones: One‐Pot Synthesis of 2‐Aryl‐2,3‐dihydro‐4H‐pyran‐4‐ones

2‐Aryl‐2,3‐dihydro‐4H‐pyran‐4‐ones were prepared in one step by cyclocondensation of 1,3‐diketone dianions with aldehydes. The use of HCl (10%) for the aqueous workup proved to be very important to avoid elimination reactions of the 5‐aryl‐5‐hydroxy 1,3‐diones formed as intermediates. The TiCl₄‐mediated cyclization of a 2‐aryl‐2,3‐dihydro‐4H‐pyran‐4‐one with 1,3‐silyloxybuta‐1,3‐diene resulted in cleavage of the pyranone moiety and formation of a highly functionalized benzene derivative.     

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.     

A novel optically active diblock copolymer composed of poly(ethylene glycol) and poly[N‐{o‐(4‐phenyl‐4,5‐dihydro‐1,3‐oxazol‐2‐yl)phenyl}maleimide]: Synthesis,micellization behavior,and chiroptical property

A series of optically active amphiphilic block copolymers were synthesizedby using potassium alkoxide of poly(ethylene glycol) monomethyl ether (MeOPEGO^?K⁺) to initiate the anionic polymerization of N‐{o‐(4‐phenyl‐4,5‐dihydro‐1,3‐oxazol‐2‐yl)phenyl}maleimide [(R)‐PhOPMI]. The PEG‐macroinitiators generated in situ in the reaction between MeOPEGOH and potassium naphthylide in tetrahydrofuran. The synthetic procedure may provide the PEG‐b‐PPhOPMI copolymers with well‐defined structure, as evidenced by gel permeation chromatography, ¹H NMR, FTIR, and elemental analysis. In particular, the preparation of block copolymers having a laevorotation or dextrorotation activity was accomplished by changing the feed composition. The micellization was examined for the amphiphilic block copolymers in aqueous milieu by fluorescence spectroscopy, dynamic light scattering, and circular dichroism. The results indicate that the copolymers could form regular spherical micelles with core‐shell structure when the hydrophilic component was long enough; in contrast, the copolymers containing shorter PEG segments formed aggregates in large dimension due to the considerable interaction between hydrophobic PPhOPMI components. Also, it was found that the aggregated structure of the polymeric micelles is strongly dependent on the medium nature and the polymer concentration. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1025–1033, 2008     

Chiral discrimination of β‐3‐homo‐amino acids using the kinetic method

Chiral discrimination of seven enantiomeric pairs of β‐3‐homo‐amino acids was studied by using the kinetic method and trimeric metal‐bound complexes, with natural and unnatural α‐amino acids as chiral reference compounds and divalent metal ions (Cu²⁺ and Ni²⁺) as the center ions. The β‐3‐homo‐amino acids were selected for this study because, first of all, chiral discrimination of β‐amino acids has not been extensively studied by mass spectrometry. Moreover, these β‐3‐homo‐amino acids studied have different aromatic side chains. Thus, the emphasis was to study the effect of the side chain (electron density of the phenyl ring, as well as the difference between phenyl and benzyl side chains) for the chiral discrimination. The results showed that by the proper choice of a metal ion and a chiral reference compound, all seven enantiomeric pairs of β‐3‐homo‐amino acids could be differentiated. Moreover, it was noted that the β‐3‐homo‐amino acids with benzyl side chains provided higher enantioselectivity than the corresponding phenyl ones. However, increasing or decreasing the electron density of the aromatic ring by different substituents in both the phenyl and benzyl side chains had practically no role for chiral discrimination of β‐3‐homo‐amino acids studied. When copper was used as the central metal, the phenyl side chain containing reference molecules (S)‐2‐amino‐2‐phenylacetic acid (L ‐Phg) and (S)‐2‐amino‐2‐(4‐hydroxyphenyl)‐acetic acid (L ‐4′‐OHPhg) gave rise to an additional copper‐reduced dimeric fragment ion, [Cu^I(ref)(A)]⁺. The inclusion of this ion improved noticeably the enantioselectivity values obtained. Copyright © 2010 John Wiley & Sons, Ltd.