Simple Approach to the Highly Stereoselective Synthesis of trans-1,2-Cyclopropane Derivatives

In the presence of KF·2H2O, furoylmethyltriphenylarsonium bromide （1a） or thienoylmethyltriphenylarsonium bromide （1b） reacted with 2-[（un）substituted benzylidene]malononitrile （2） in chloroform at room temperature to give trans-3,3-dicyano-1-furoyl-2-[（un）substituted phenyl]cyclopropane （3a） or trans-3,3-dicyano-1-thienoyl-2- [（un）substituted phenyl]cyclopropane （3b） respectively in good yield with high stereoselectivity. The structures of product 3 were confirmed by IR, MS, 1^H NMR, 1^H-1^H COSY and microanalysis. The relative configuration of product 3 was determined by 1^H-1^H NOESY technique. The mechanism for the formation of product 3 was also proposed.     

Synthesis of well‐defined azide‐terminated poly(vinyl alcohol) and their subsequent modification via click chemistry

A new azide‐functionalized xanthate, S‐(4‐azidomethylbenzyl) O‐(2‐methoxyethyl) xanthate, was synthesized and used to mediate the reversible addition fragmentation chain transfer polymerization of vinyl acetate. The polymerization was demonstrated to be controlled, and well‐defined PVAc with α‐azide, ω‐xanthate groups were obtained, the xanthate groups of which were further removed by radical‐induced reduction with lauroyl peroxide in the presence of excess 2‐propanol. Hydrolysis of α‐azide‐terminated PVAc (N₃‐PVAc) led to the formation of the corresponding α‐azide‐terminated PVA (N₃‐PVA). Finally, end‐modification of N₃‐PVA by click chemistry with alkyne‐end‐capped poly(caprolactone) (A‐PCL), alkynyl‐mannose, and alkynyl‐pyrene was carried out to obtain a new block copolymer PCL‐b‐PVA, and two PVA with mannose or pyrene as the end functional groups. The polymers were characterized by gel permeation chromatography, ¹H NMR spectroscopy, and FTIR. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 4494–4504, 2009     

Synthesis and Biological Study of Some 4-oxo-Thiazolidine Derivatives of 2-Aminothiazole

Conventional and microwave assisted synthesis of new series of N‐[2‐{2‐(substituted phenyl)‐4‐oxo‐5‐(substituted benzylidene)‐1,3‐thiazolidine}‐iminoethyl]‐2‐aminothiazole 5a–5m have been developed. The cycloaddition reaction of thioglycolic acid with N‐{2‐(substituted benzylidenehydrazino)‐ethyl}‐2‐aminothiazole 3a–3m in the presence of anhydrous ZnCl₂ afforded new heterocyclic compounds N‐[2‐{2‐(substituted phenyl)‐4‐oxo‐1,3‐thiazolidine}‐iminoethyl]‐2‐aminothiazole 4a–4m . The later product on treatment with several selected substituted aromatic aldehydes in the presence of C₂H₅ONa undergoes Knoevenagel reaction to yield 5a–5m . The structures of compounds 1 , 2 , 3a–3m , 4a–4m and 5a–5m were confirmed by IR, ¹H NMR, ¹³C NMR, FAB‐Mass and chemical analysis. All above compounds were screened for their antimicrobial activities against some selected bacteria and fungi and antituberculosis study against M. tuberculosis.     

Synthesis of 1‐[(1R)‐1‐(6‐fluoro‐1,3‐benzothiazol‐2‐yl)ethyl]‐3‐substituted phenyl ureas and their inhibition activity to acetylcholinesterase and butyrylcholinesterase

A series of novel 1‐[(1R)‐1‐(6‐fluoro‐1,3‐benzothiazol‐2‐yl)ethyl]‐3‐substituted phenyl ureas were synthesized by the condensation of (1R)‐1‐(6‐fluoro‐1,3‐benzothiazol‐2‐yl)ethanamine with substituted phenyl isocyanates under mild conditions. Their structures were confirmed ¹H, ¹³C, and ¹⁹F NMR spectra, and elemental analyses. The optical activities were confirmed by optical rotation measurements. The inhibition activity of 1‐[(1R)‐1‐(6‐fluoro‐1,3‐benzothiazol‐2‐yl)ethyl]‐3‐substituted phenyl ureas to acetylcholinesterase (ACHE) and butyrylcholinesterase (BCHE) was also tested. Preliminary bioassay indicated that the target ureas displayed excellent acetylcholinesterase and butyrylcholinesterase inhibition activity. J. Heterocyclic Chem., 2011.     

Convenient Synthesis of 1H‐Indol‐1‐yl Boronates via Palladium(0)‐Catalyzed Borylation of Bromo‐1H‐indoles with ‘Pinacolborane’

An atom‐economic Pd⁰‐catalyzed synthesis of a series of pinacol‐type indolylboronates 3 from the corresponding bromoindole substrates 2 and pinacolborane (pinBH) as borylating agent was elaborated. The optimal catalyst system consisted of a 1 : 2 mixture of [Pd(OAc)₂] and the ortho‐substituted biphenylphosphine ligand L‐3 (Scheme 4, Table). Our synthetic protocol was applied to the fast, preparative‐scale synthesis of 1‐substituted indolylboronates 3a – h in the presence of different functional groups, and at a catalyst load of only 1 mol‐% of Pd.     

Synthesis,Pharmacological, and Biological Screening of Novel Derivatives of Benzodiazepines

A series of novel 4‐(substituted phenyl)‐2‐(thiophen‐2‐yl)‐2,3‐dihydro‐1H‐benzo[b][1,4]diazepine have been synthesized from 3‐(substituted phenyl)‐1‐(thiophen‐2‐yl)prop‐2‐en‐1‐one. 3‐(Substituted phenyl)‐1‐(thiophen‐2‐yl)prop‐2‐en‐1‐one was prepared by condensing 2‐acetyl thiophene with various aromatic aldehydes in the presence of 20% NaOH as base. Different 3‐(substituted phenyl)‐1‐(thiophen‐2‐yl)prop‐2‐en‐1‐one on cyclization with o‐phenylenediamine in the presence of NaOH as base resulted in 4‐(substituted phenyl)‐2‐(thiophen‐2‐yl)‐2,3‐dihydro‐1H‐benzo[b][1,4]diazepine derivatives. The structures of synthesized compounds are confirmed by IR, ¹H NMR, mass spectra, and elemental analysis. All the compounds have been screened for their antimicrobial, analgesic, and anti‐inflammatory activities.     

A Facile Synthesis of Oxoindenothiazine and Dioxospiro(indene‐2,4′‐thiazine) Derivatives from (Substituted ethylidene)hydrazinecarbothioamides

(E)‐2‐[2‐(1‐Substituted ethylidene)hydrazinyl]‐5‐oxo‐9b‐hydroxy‐5,9b‐dihydroindeno[1,2‐d][1,3]‐thiazine‐4‐carbonitriles and (E)‐5‐oxo‐[(E)‐(1‐substituted ethylidene)hydrazinyl]‐2,5‐dihydroindeno[1,2‐d][1,3]thiazine‐4‐carbonitriles have been obtained from the reaction of 2‐(substituted ethylidene)hydrazinecarbothioamides with 2‐(1,3‐dioxo‐2,3‐dihydro‐1H‐inden‐2‐ylidene)propanedinitrile ( 1 ) in ethyl acetate solution. However, (Z)‐6′‐amino‐1,3‐dioxo‐3′‐substituted‐2′‐[(E)‐(1‐phenylethylidene)hydrazono]‐1,2′,3,3′‐tetrahydrospiro(indene‐2,4′‐[1,3]thiazine)‐5′‐carbonitriles were observed during the reaction of N‐substituted‐2‐(1‐phenylethylidene)hydrazinecarbothioamides with ( 1 ). The structure assignment of products has been confirmed on the basis of ¹H‐, ¹³C‐NMR, and mass spectrometry, as well as theoretical calculations.     

Synthesis,Modification, and Anticonvulsant Activity of 3′‐R1‐Spiro[indoline‐3,6′‐[1,2,4]triazino[2,3‐c]quinazolin]‐2,2′(7′H)‐diones Derivatives

Previously unknown 3′‐R¹‐5‐R²‐spiro[indoline‐3,6′‐[1,2,4]triazino[2,3‐c]quinazoline]‐2,2′‐(7′H)‐diones and their N‐substituted analogues were obtained via reaction of 6‐R¹‐3‐(2‐aminophenyl)‐1,2,4‐triazin‐5‐ones with isatin and its substituted derivatives. It was shown that alkylation of 3′‐R¹‐5‐R²‐spiro[indoline‐3,6′‐[1,2,4]triazino[2,3‐c]quinazolin]‐2,2′‐(7′H)‐diones by N‐R³‐chloroacetamides or chloroacetonitrile in the presence of а base proceeds by N‐1 atom of isatin fragment. The spectral properties (¹H and ¹³C NMR spectra) of synthesized compounds were studied, and features of spectral patterns were discussed. The high‐effective anticonvulsant and radical scavenging agents among 3′‐R¹‐5‐R²‐spiro[indoline‐3,6′‐[1,2,4]triazino[2,3‐c]quinazolin]‐2,2′(7′H)‐diones and their N‐substituted derivatives were detected. It was shown that compounds 2.2 , 2.8 , and 3.1 exceed or compete the activity of the most widely used in modern neurology drug—lamotrigine on the pentylenetetrazole‐induced seizures model. The aforementioned fact may be considered as a reason for further profound study of synthesized compounds using other pathology models.     

立体选择性合成2-(a-噻吩甲酰基)-3-取代苯基-4-乙氧羰基-5-甲基-反式-2,3-二氢呋喃

溴化(a-噻吩甲酰基)甲基三苯鉮1与3-取代苯甲叉基-2,4-戊二酮 2以碳酸钾为碱,在苯中55℃条件下反应,可以较好的收率、高立体选择性地生成反-2-(a-噻吩甲酰基)-3-取代苯基-4-乙氧羰基-5-甲基-2,3-二氢呋喃3。产物结构均经波谱予以确定。本文还提出了生成产物的可能机理。     

Theoretical Study on Gas—phase Pyrolytic Reactions of N—Ethyl,Isopropyl and N—t—Butyl Substituted 2—Aminopyrazine

Density functional theory (DFT) and ab initio methods were used to study gas‐phase pyrolytic reaction mechanisms of iV‐ethyl, N‐isopropyl and N‐t‐butyl substituted 2‐aminopyrazine at B3LYP/6–31G* and MP2/6–31G*, respectively. Single‐point energies of all optimized molecular geometries were calculated at B3LYP/6–311 + G(2d,p) level. Results show that the pyrolytic reactions were carried out through a unimolecular first‐order mechanism which were caused by the migration of atom H(17) via a six‐member ring transition state. The activation energies which were verified by vibrational analysis and correlated with zero‐point energies along the reaction channel at B3LYP/6–311 + G(2d,p) level were 252.02 kJ. mo^?1 (N‐ethyl substituted), 235.92 kJ‐mol^?1 (N‐t‐isopropyl substituted) and 234.27 kJ‐mol^?1 (N‐t‐butyl substituted), respectively. The results were in good agreement with available experimental data.     

Relaxivity and Transmetallation Stability of New Benzyl‐Substituted Derivatives of Gadolinium?DTPA Complexes

In our efforts of finding new specific contrast agents of higher relaxivity and selectivity, we have prepared the two new benzyl‐functionalized DTPA (‘diethylenetriamine pentaacetate’) gadolinium complexes (S)‐ 3 and (R,S)‐ 4 , and compared their properties with those of the known regioisomers (S)‐ 2 and (S)‐ 1 . The theoretical fitting of the reduced transverse relaxation rates of the ¹⁷O‐nucleus of H₂O gave values for the water‐residence time (τ_M) of 86–143 ns at 310 K, values that are not limiting the proton relaxivity at body temperature. ¹H‐NMRD (nuclear magnetic‐relaxation dispersion) Profiles showed that the relaxivity of 1 – 4 (r₁=4.3–5.1 s^?1 mM ^?1 at 20 MHz and 310 K) is higher than for the Gd? DTPA parent compound 5 . Transmetallation assessment demonstrated that all substituted compounds, except for (S)‐ 2 , are more stable than 5 . The highest stability towards Zn²⁺‐induced transmetallation was achieved with complexes 3, 1 , and 4 (in decreasing order). Apparently, the steric hindrance of the benzyl substituents in positions 5, 4, and 2, respectively, favorably reduces the accessibility of Zn ions. From a synthetic point of view, 4‐substituted DTPA complexes of type 1 are more readily accessible than 5‐substituted compounds of type 3 . Therefore, the former seem to be superior for linking substituted DTPA complexes to macromolecules or specific vectors.     

Copolymerization of poly(vinyl alcohol)‐graft‐poly(1,4‐dioxan‐2‐one) with designed molecular structure by a solid‐state polymerization method

Poly(vinyl alcohol)‐graft‐poly(1,4‐dioxan‐2‐one) (PVA‐g‐PPDO) with designed molecular structure was synthesized by a solid‐state polymerization. The solid‐state copolymerization was preceded by a graft copolymerization of PDO initiated with PVA as a multifunctional initiator, and Sn (Oct)₂ as a coininitiator/catalyst in a homogeneous molten state. The polymerization temperature was then decreased and the copolymerization was carried out in a solid state. The products prepared by solid‐state polymerization were characterized by ¹H NMR and DSC, and were compared with those synthesized in the homogeneous molten state. The degree of polymerization (D_p), degree of substitution (D_s), yield and the average molecular weight of the graft copolymer with different molecular structure were calculated from the ¹H NMR spectra. The results show that the crystallization process during the solid‐state polymerization may suppress the undesirable inter‐ or intramolecular side reactions, then resulting in a controlled molecular structure of PVA‐g‐PPDO. The results of DSC measurement show that the molecular structures determine the thermal behavior of the PVA‐g‐PPDO. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 3083–3091, 2006     

Synthesis of Thieno[2,3‐b]quinolinone Derivatives

The Knoevenagel reactions of malononitrile with acetophenone or 4‐substituted acetophenons were carried to give the corresponding 2‐(1‐aryle thylidene)malononitriles, which was further cyclized with sulfur using NaHCO₃ as catalysts to generate 2‐amino‐5‐arylthiophene‐3‐carbonitrile 2 . The intermediate enamines 3 were prepared by refluxing of 2 with 5‐substituted‐1,3‐cyclohexanedione using p‐toluenesulfonic acid as catalyst. The title compounds 4‐amino‐3‐aryl ‐7‐substituted‐7,8‐dihydrothieno[2,3‐b]quinolin‐5(6H)‐one were synthesized by cyclization of 3 in the presence of K₂CO₃ and Cu₂Cl₂. The structures of all compounds were characterized by elemental analysis, IR, MS, and ¹H‐NMR spectra.     

Reactivity study on morpholine‐1‐carbothioic acid (2‐phenyl‐3H‐quinazolin‐4‐ylidene) amide

Regioselective reactions of morpholine‐1‐carbothioic acid (2‐phenyl‐3H‐quinazolin‐4‐ylidene) amide ( 1 ) with electrophiles and nucleophiles were studied. The compound ( 1 ) reacts with alkyl halides in basic medium to afford S‐substituted isothiourea derivatives, with amines to give 1,1‐disubstituted‐3‐(2‐phenyl‐3H‐quinazolin‐4‐ylidene) thioureas and l‐substituted‐3‐(2‐phenyl‐quinazolin‐4‐yl) thioureas via transami‐nation reaction. The reaction of ( 1 ) with amines in the presence of H₂O₂ provided N⁴‐disubstituted‐N'⁴‐(2‐phenylquinazolin‐4‐yl)morpholin‐4‐carboximidamide via oxidative desulfurization. Estimation of reactivity sites on ( 1 ) was supported using the ab initio (HF/6‐31G**) quantum chemistry calculations. The ir, ¹H nmr, ¹³C nmr, mass spectroscopy and x‐ray identified the isolated products.     

1H and 13C NMR spectral assignments of novel chromenylchalcones

Several types of chalcones containing 2H‐chromen group were synthesized. Claisen–Schmidt condensation of 2H‐chromen‐3‐carbaldehydes (I) with methoxy substituted acetophenones afforded (E)‐3‐(2H‐chromen‐3‐yl)‐1‐(methoxyphenyl)prop‐2‐en‐1‐ones (chromenylchalcones, 1–7). Other types of chromenylchalcone, (E)‐1‐(6‐methoxy‐2H‐chromen‐3‐yl)‐3‐(methoxyphenyl)prop‐2‐en‐1‐ones (8–13) were also obtained between reaction of methoxy substituted benzaldehydes and 1‐(6‐methoxy‐2H‐chromen‐3‐yl)ethanone (II). Dichromenylchalcones (14–16) were also synthesized through the same reaction between aldehydes (I) and ketone (II). Their complete ¹H‐NMR and ¹³C‐NMR assignments are reported here and more polysubstituted chromenylchalcones synthesized or isolated from the natural sources in the future can be identified on the basis of the NMR data reported here. Copyright © 2012 John Wiley & Sons, Ltd.     

Synthesis and spectral properties of 2‐[(o‐ and p‐substituted)aminophenyl] ‐3H‐5‐[(o‐ and p‐substituted)phenyl]‐7‐chloro‐1,4‐benzodiazepines

A series of twelve new 2‐[(o‐ and p‐substituted)aminophenyl]‐3H‐5‐[(o‐ and p‐substituted)phenyl]‐7‐chloro‐1,4‐benzodiazepines, which have possible pharmacological properties has been obtained. The synthesis was carried out following six steps. The structure of all products was corroborated by ir, ¹H nmr, ¹³C nmr and ms. In addition for the compound 2‐(o‐chloroaminophenyl)‐3H‐5‐(o‐fluorophenyl)‐7‐chloro‐1,4‐benzodiazepine 7, its structure was confirmed by X‐ray diffraction.     

Revisit to the photocrosslinking behavior of PVA‐SbQ as a water‐soluble photopolymer with anomalously low contents of quaterized stilbazol side chains

The photocrosslinking behavior of poly(vinyl alcohol) (PVA) substituted with 0.1, 0.3, 1.3, and 4.0 mol % of styrylpyridinium (SbQ) (PVA‐SbQs) side chains was reinvestigated. Even‐order derivative spectra of films of PVAs loaded with 0.1 and 0.3 mol % of SbQ revealed the presence of subpeaks owing to vibrational transitions, whereas PVA bearing 1.3 and 4.0 mol % of SbQ displayed a new blue‐shifted band (H‐band) at 328 nm due to H‐aggregation. Changes in derivative spectra disclosed the rapid disappearance of the H‐band of PVA‐SbQs under UV irradiation within exposure doses of 10 mJ cm^?2. On the other hand, the films of the PVA‐SbQs were insolubilized upon UV irradiation at exposure doses of 2 and 3 mJ cm^?2, respectively, leading to the conclusion that the high photosensitivity comes from the photodimerization of H‐aggregate as a ground‐state dimer. Fluorescence measurements implied the presence of J‐aggregate at 386 nm, but the involvement of the J‐aggregation in photocrosslinking was excluded because of its negligible fraction. A photosensitive emulsion of poly(vinyl acetate) emulsified with PVA‐SbQ exhibited similar changes in higher‐order derivative spectra in film and applied to fabricate a stencil for screen printing with aid of an LED‐emitting 375 nm light. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis,Characterization, and Biological Evaluation of Some Tri‐Substituted Imidazole/thiazole Derivatives

A novel compound series of tri‐substituted imidazole/thiazole derivatives ( 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h , 3i ) were prepared by Radziszewski reaction. Benzil ( 1 ), ammonium acetate or ammonium thiocynate, and 1‐phenyl‐3‐(p‐substituted phenyl)‐1H‐pyrazole‐4‐carbaldehyde ( 2a , 2b , 2c , 2d , 2e , 2f , 2g ) were reacted to give the desired product. Synthesized compounds were characterized by elemental analysis (CHNS) and spectral analysis (FTIR, ¹H and ¹³C FT NMR, and LC–MS). All the compounds were screened for their antibacterial, antifungal, and antimycobacterial activities. Antimicrobial activity was evaluated against some bacterial strains such as Escherichia coli (MTCC 443), Pseudomonas aeruginosa (MTCC 1688), Staphylococcus aureus (MTCC 96), Streptococcus pyogenes (MTCC 442), and the H₃₇Rv strain of Mycobacterium tuberculosis, and the fungal activity was observed against strains, for example, Candida albicans (MTCC 227), Aspergillus niger (MTCC 282), and Aspergillus clavatus (MTCC 1323). All the synthesized compounds were found to possess moderate to excellent activity against the above selected strains.     

1-萘甲酰苯胺和2-萘甲酰苯胺的分子内电荷转移研究

A series of 1-naphthanilides (1) and 2-naphthanilides (2) with varied substituents at the para- or meta-position of anilino phenyl ring were prepared and their absorption and fluorescence spectra in a nonpolar solvent cyclohexane were investigated. An abnormal long wavelength emission assigned to the charge transfer (CT) state was found for all of the prepared naphthanilides in cyclohexane. A linear free energy correlation between the CT emission energies and the Hammett constants of the substituent was found within series 1 and 2. The value of the linear slope with 1 (0.42 eV) was higher than that with 2 (0.32 eV) being close to that of the substituted benzanilides 3 (0.31 eV) The higher slope value suggested higher charge separation extent in the CT state of 1 than that of 2. It was found that the corresponding linear slope of anilino-substituted benzanilides remained unchanged when para-, meta-, ortho-, or ortho, ortho-methyls were introduced into the anilino moiety, which ruled out the possible contribution of the difference in the steric effect and the electron accepting ability of the naphthoyl acceptor in 1 and 2. Compared with the early reported N-substituted-benzoyl-aminonaphthalene derivatives 4 and 5, it was considered that 1-naphthoyl enhanced the charge transfer in 1 and the proximity of its ^1La and ^1Lb states was suggested to be responsible. It was shown that 1- and/or 2-substituted naphthalene cores acting as either electron acceptor (naphthoyl) or electron donor (aminonaphthalene) were different in not only electron accepting (donating) ability but also shaping the charge transfer pathway.     

Synthetic Receptors for the High‐Affinity Recognition of O‐GlcNAc Derivatives

The combination of a pyrenyl tetraamine with an isophthaloyl spacer has led to two new water‐soluble carbohydrate receptors (“synthetic lectins”). Both systems show outstanding affinities for derivatives of N‐acetylglucosamine (GlcNAc) in aqueous solution. One receptor binds the methyl glycoside GlcNAc‐β‐OMe with K_a≈20 000 m ^?1, whereas the other one binds an O‐GlcNAcylated peptide with K_a≈70 000 m ^?1. These values substantially exceed those usually measured for GlcNAc‐binding lectins. Slow exchange on the NMR timescale enabled structural determinations for several complexes. As expected, the carbohydrate units are sandwiched between the pyrenes, with the alkoxy and NHAc groups emerging at the sides. The high affinity of the GlcNAcyl–peptide complex can be explained by extra‐cavity interactions, raising the possibility of a family of complementary receptors for O‐GlcNAc in different contexts.