Green Synthesis of 1‐(1,2,4‐Triazol‐4‐yl)spiro[azetidine‐2,3′‐(3H)indole]‐2′,4′(1′H)‐diones as Potential Insecticidal Agents

One pot green synthesis of 1‐(1,2,4‐triazol‐4‐yl)spiro[azetidine‐2,3′‐(3H)‐indole]‐2′,4′(1′H)‐diones was carried out by the reaction of indole‐2,3‐diones,4‐amino‐4H‐1,2,4‐triazole and acetyl chloride/chloroacetyl chloride in ionic liquid [bmim]PF₆ with/without using a catalyst. It was also prepared by conventional method via Schiff's bases, 3‐[4H‐1,2,4‐triazol‐4‐yl]imino‐indol‐2‐one. Further, the corresponding phenoxy derivatives were obtained by the reaction of chloro group attached to azetidine ring with phenols. The synthesized compounds were characterized by analytical and spectral (IR, ¹H NMR, ¹³C NMR, and FAB mass) data. Evaluation for insecticidal activity against Periplaneta americana exhibited promising results.     

One‐Pot Syntheses of 2‐(2‐Sulfanyl‐4H‐3,1‐benzothiazin‐4‐yl)acetic Acid Derivatives via Reactions of 3‐(2‐Isothiocyanatophenyl)prop‐2‐enoic Acid Derivatives with Thiols or Sodium Sulfide

Two efficient methods for the preparation of 2‐(2‐sulfanyl‐4H‐3,1‐benzothiazin‐4‐yl)acetic acid derivatives 3 under mild conditions have been developed. The first method is based on the reaction of 3‐(2‐isothiocyanatophenyl)prop‐2‐enoates 1a – 1c with thiols in the presence of Et₃N in THF at room temperature, leading to the corresponding dithiocarbamate intermediates 2 , which underwent spontaneous cyclization at the same temperature by an attack of the S‐atom at the prop‐2‐enoyl moiety in a 1,4‐addition manner (Michael addition) to give 2‐(2‐sulfanyl‐4H‐3,1‐benzothiazin‐4‐yl)acetates in one pot. The second method involves treatment of 3‐(2‐isothiocyanatophenyl)prop‐2‐enoic acid derivatives 1b – 1d with Na₂S leading to the formation of 2‐(2‐sodiosulfanyl‐4H‐3,1‐benzothiazin‐4‐yl)acetic acid intermediates 5 by a similar addition/cyclization sequence, which are then allowed to react with alkyl or aryl halides to afford derivatives 3 . 2‐(2‐Thioxo‐4H‐3,1‐benzothiazin‐4‐yl)acetic acid derivatives 6 can be obtained by omitting the addition of halides.     

Synthesis,spectral, and antimicrobial studies of 1‐butyl‐3‐substituted‐4‐(2‐aryl‐1H‐indol‐3‐yl)‐2‐azetidinones

Ketene generated from acetyl chloride or chloroacetyl chloride adds on indolyl Schiff's base double bond to afford 1‐butyl‐3‐substituted‐4‐(2‐aryl‐1H‐indol‐3‐yl)‐2‐azetidinones in THF. The reaction proceeds stereospecifically via concerted trans [2+2] cycloaddition. The synthesized compounds have been characterized by elemental analyses and spectral data (IR, PMR, and mass). All synthesized compounds have been evaluated for antibacterial and antifungal activities, and 4g to 4l have shown promising results. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:494–501, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20052     

Synthesis and Cytotoxic Evaluation of Novel 1,2,3‐Triazole‐4‐Linked (2E,6E)‐2‐Benzylidene‐6‐(4‐nitrobenzylidene)cyclohexanones

This work describes the synthesis of novel 1,2,3‐triazole‐4‐linked (2E,6E)‐2‐benzylidene‐6‐(4‐nitrobenzylidene)cyclo‐hexanones starting from cyclohexanone. 1‐(Cyclohex‐1‐en‐1‐yl)piperidine, the enamine from cyclohexanone and piperidine, reacted with 4‐nitrobenzaldehyde to obtain 2‐(4‐nitrobenzylidene)cyclohexanone. Condensation of the latter compound with (prop‐2‐yn‐1‐yloxy)benzaldehyde derivatives under acidic conditions gave (4‐nitrobenzylidene)‐[(prop‐2‐yn‐1‐yloxy)‐benzylidene]cyclohexanones. Finally, ‘click reaction’ of these derivatives and various organic azides led to the title compounds. All compounds were examined by MTT assay for cytotoxic activity in one human breast cancer cell line, MDA‐MB‐231.     

CuBr/Et3N‐Promoted Reactions of 2‐Aminobenzamides and Isothiocyanates: Efficient Synthesis of Novel Quinazolin‐4(3H)‐ones

A series of novel quinazolin‐4(3H)‐one derivatives were efficiently synthesized starting from isatoic anhydride. First, reaction of isatoic anhydride and amines in H₂O at room temperature afforded 2‐aminobenzamides. Then, CuBr/Et₃N promoted reaction of 2‐aminobenzamides and different aryl isothiocyanates in DMF at 80° afforded the title compounds in good yield.     

Synthesis of 4-(4-Methylsulfonylphenyl)-3-phenyl-2(3H)-thiazole Thione Derivatives as New Potential COX-2 Inhibitors

Synthesis of novel 4-（4-methylsulfonylphenyl）-3-phenyl-2（3H）-thiazole thione derivatives with functionalized diarylheterocycle pharmacophore as potential COX-2 inhibitors was described. The title compounds were synthesized by cyclocondensation of corresponding dithiocarbamate and 2-bromo-1-（4-methylsulfonylphenyl）ethanone, followed by dehydration with H2SO4. All of the target compounds were characterized by ^1H NMR, IR and mass spectral data.     

N‐Heterocyclic Carbene Iron(III) Porphyrin‐Catalyzed Intramolecular C(sp3)–H Amination of Alkyl Azides

Metal‐catalyzed intramolecular C?H amination of alkyl azides constitutes an appealing approach to alicyclic amines; challenges remain in broadening substrate scope, enhancing regioselectivity, and applying the method to natural product synthesis. Herein we report an iron(III) porphyrin bearing axial N‐heterocyclic carbene ligands which catalyzes the intramolecular C(sp³)–H amination of a wide variety of alkyl azides under microwave‐assisted and thermal conditions, resulting in selective amination of tertiary, benzylic, allylic, secondary, and primary C?H bonds with up to 95 % yield. 14 out of 17 substrates were cyclized selectively at C4 to give pyrrolidines. The regioselectivity at C4 or C5 could be tuned by modifying the reactivity of the C5–H bond. Mechanistic studies revealed a concerted or a fast re‐bound mechanism for the amination reaction. The reaction has been applied to the syntheses of tropane, nicotine, cis‐octahydroindole, and leelamine derivatives.     

2(S)‐Amino‐3‐[1H‐imidazol‐4(5)‐yl]­propyl cyclo­hexylmethyl ether di­hydro­chloride and 2(S)‐amino‐3‐[1H‐imidazol‐4(5)‐yl]­propyl 4‐bromo­benzyl ether di­hydro­chloride

(Cyclo­hexyl­methyl­oxy­methyl)(1H‐imidazol‐4‐io­methyl)‐(S)‐ammonium dichloride, C₁₃H₂₅N₃O⁺·2Cl^?, and (4‐bromo­benzyl)(1H‐imidazol‐4‐io­methyl)‐(S)‐ammonium dichloride, C₁₃H₁₈BrN₃O⁺·2Cl^?, are model compounds with different biological activities for evaluation of the hist­amine H3‐receptor activation mechanism. Both title compounds occur in almost similar extended conformations.     

One‐Pot Synthesis of 2‐Substituted 4‐Aryl‐4,5‐dihydro‐3,1‐benzoxazepines from 2‐(2‐Aminophenyl)‐1‐arylethanols via Dehydration of the Corresponding Amides

An efficient method for the preparation of 2‐substituted 4‐aryl‐4,5‐dihydro‐3,1‐benzoxazepine derivatives under mild conditions has been developed. The reaction of 2‐(2‐aminophenyl)ethanols 1 with acid chlorides in the presence of excess Et₃N in THF at room temperature gave the corresponding N‐acylated intermediates 2 , which were dehydrated by treatment with POCl₃ to give 2‐substituted 4‐aryl‐4,5‐dihydro‐3,1‐benzoxazepines 3 in a one‐pot reaction.     

Thionation of N‐(ω‐Halogenoalkyl)‐Substituted Amides with Lawesson's Reagent: Facile Synthesis of 4,5‐Dihydro‐1,3‐thiazoles and 5,6‐Dihydro‐4H‐1,3‐thiazines

The thionation and cyclization of N‐(ω‐halogenoalkyl)‐substituted amides (and related compounds) with Lawesson's reagent (LR=2,4‐bis(4‐methoxyphenyl)‐1,3,2,4‐dithiadiphosphetane 2,4‐disulfide) has been investigated. Treatment of the amides 1 with LR gave the corresponding thioamides 2 in moderate to good yields (Table). The latter, upon treatment with base, afforded, either in a separate step or in a one‐pot procedure, the cyclized title compounds, i.e., the 4,5‐dihydro‐1,3‐thiazoles 3 or the corresponding 5‐6‐dihydro‐4H‐thiazines 4 via dehydrohalogenation.     

Crystallographic report: Crystal structure of bis(2,4,6‐tri‐tert‐butylphenolato‐O) bis(tetrahydrofuran‐O) samarium (N,N‐η2‐azobenzene) diethyl ether solvate

Reaction of divalent Sm(OAr)₂(THF)₃ (Ar = C₆H₂‐tert‐Bu₃‐2,4,6; THF = tetrahydrofuran) with one equivalent of azobenzene in THF and crystallization of the product in diethyl ether afforded the title complex (ArO)₂(THF)₂Sm(η²‐N₂Ph₂)·Et₂O in good yield. In the complex, the N? N bond length for the azobenzene species is lengthened. The two Sm? N bonds are equivalent, and their bond lengths are intermediate between the donor bond and the single bond. Copyright © 2005 John Wiley & Sons, Ltd.     

Controlled Anionic Synthesis of Poly[2‐(3‐nitrocarbazolyl)ethyl methacrylate]

Poly[2‐(3‐nitrocarbazolyl)ethyl methacrylate] (poly(NCzMA)) with controlled molecular weight and narrow molecular weight distribution was successfully synthesized using (methyl methacryloyl)potassium (MMA) as a weak initiator in the presence of diethylzinc (Et₂Zn) in THF at –78°C. Et₂Zn acted both as an additive for the coordination with enolate anion and nitro group and as a scavenger to remove impurities. Block copolymers PMMA‐block‐poly(NCzMA)‐block‐PMMA and poly(NCzMA)‐block‐PS‐block‐poly(NCz‐MA), were also synthesized quantitatively (PMMA: poly(methyl methacrylate), PS: polystyrene). The results indicate that Et₂Zn can be used to synthesize the polymers of solid, nitro group‐containing methacrylate monomers by anionic polymerization in THF.     

Synthesis and Pharmacological Evaluation of a Novel Series of 2‐((2‐Aryl thiazol‐4‐yl)methyl)‐5‐(alkyl/alkylnitrile thio)‐1,3,4‐oxadiazole Derivatives as Possible Antifungal Agents

In the present investigation, a novel series of 2‐[(2‐arylthiazol‐4‐yl)methyl]‐5‐(alkyl/alkylnitrile thio)‐1,3,4‐oxadiazole derivatives were synthesized by cyclo‐condensation of 2‐(2‐substituted thiazol‐4‐yl)aceto hydrazide with carbon disulfide followed by S‐alkylation with alkyl halide in dry acetone. All the newly synthesized compounds were characterized by spectral (IR, ¹H NMR, ¹³C NMR, mass, and elemental analysis) methods. The title compounds were screened for in vitro antifungal activity and most of the synthesized compounds show moderate to good antifungal activity.     

Synthesis and Bioactivities of Novel N‐(4‐(2‐Aryloxythiazol‐5‐yl)but‐3‐yn‐2‐yl)benzamides

A series of novel N‐(4‐(2‐aryloxythiazol‐5‐yl)but‐3‐yn‐2‐yl)benzamide derivatives were designed and synthesized. Their structures were identified by ¹H NMR and elemental analyses. Preliminary bioassays indicated that some title compounds provided >80% control of Sclerotinia sclerotiorum at 50 µg/mL and >70% herbicidal activities against B. campestris at 100 µg/mL. Their structure‐activities relationships were also discussed.     

Synthesis of alkyl 6‐methyl‐4‐(2‐trifluoromethylphenyl)‐1,2,3,4‐tetrahydro‐2H‐pyrimidine‐2‐one‐5‐carboxylates possessing a N‐3 nitro substituent to determine calcium channel modulation structure‐activity relationships

The Bigenelli acid catalyzed condensation of 2‐trifluoromethylbenzaldehyde ( 1 ), urea ( 2 ) and an alkyl acetoacetate ( 3 ) afforded the respective alkyl (Me, Et, i‐Pr, i‐Bu) 6‐methyl‐4‐(2‐trifluoromethylphenyl)‐1,2,3,4‐tetrahydro‐2H‐pyrimidine‐2‐one‐5‐carboxylate ( 4‐7 ). Subsequent N³‐nitration of the alkyl esters ( 4‐7 ) using Cu(NO₃)₂ 3H₂O and Ac₂O furnished the target alkyl 6‐methyl‐3‐nitro‐4‐(2‐trifluoromethylphenyl)‐1,2,3,4‐tetrahydro‐2H‐pyrimidine‐2‐one‐5‐carboxylates ( 8‐11 ). The N³‐nitro compounds ( 8‐11 ) were less potent calcium channel antagonists (IC₅₀ values in the 1.9 × 10^?7 to 3.9 × 10^?6 M range) on guinea pig ileal longitudinal smooth muscle than the reference drug nifedipine (Adalat®, IC₅₀ = 1.4 × 10^?8 M). In vitro calcium channel modulation studies on guinea pig left atrium (GPLA) showed that the methyl and ethyl esters ( 8‐9 ) induced a weak‐to‐modest positive inotropic (agonist) effect, and that the inactive isopropyl ( 10 ) and isobutyl ( 11 ) esters did not alter the cardiac contractile force of GPLA.     

Synthesis and Herbicidal Activities of 3‐(4‐Chloro‐2‐fluoro‐5‐substituted phenyl)benzo[d][1,2,3]triazin‐4(3H)‐one Derivatives

A series of 3‐phenyl benzo[d][1,2,3]triazin‐4(3H)‐one derivatives were synthesized through the condensation of phenol E and alkyl (alkenyl, alkynyl) chlorides (bromides, iodide) or alkyl chloroacetates or N‐alkyl chloroacetamides using K₂CO₃ as the acid acceptor in N,N‐dimethylformamide. Phenol E was prepared from starting material, 5‐amino‐2‐chloro‐4‐fluorophenyl ethyl carbonate, in four steps involving in amidation, reduction, diazotization, and deprotecting‐group reaction. The herbicidal activities of the title compounds were tested against two dicotyledonous plants and two monocotyledonous plants, in which some of them exhibited high herbicidal activities against two dicotyledonous plants in preemergence and postemergence treatments. Moreover, when the dosage was decreased to 180 and 90 g/ha, compounds F1 , F8 , and F9 showed highly selective inhibitory activities against amaranth pigweed, alfalfa, asteraceae, field sowthistle, morning glory, purslane, and velvetleaf in postemergence treatment but had no herbicidal efficacy on rape except F1 , suggesting that it be possible to find a kind of herbicides to inhibit dicotyledonous weeds in the field of dicotyledonous crops with the same genus as aforementioned weeds.     

Facile Synthesis of N‐(Benzyl‐1H‐1,2,3‐Triazol‐5‐yl) Methyl)‐4‐(6‐Methoxybenzo [d] Thiazol‐2‐yl)‐2‐Nitrobenzamides via Click Chemistry

A series of novel N‐((l‐benzyl‐lH‐l,2,3‐triazol‐5‐yl) methyl)‐4‐(6‐methoxy benzo[d ]thiazol‐2‐yl)‐2‐nitrobenzamide derivatives were prepared from 4‐(6‐methoxybenzo[d ]thiazol‐2‐yl)‐2‐nitro‐N‐(prop‐2‐ynyl) benzamide with benzyl azides by using click reaction (copper‐catalyzed Huisgen 1,3‐dipolar cycloaddition reaction) in the presence of CuSO₄.5H₂O and sodium ascaorbate. All the newly synthesized compounds were evaluated further in vitro antimicrobial activity against Gram‐positive bacteria (Staphylococcus aureus and Bacillus subtillis ), Gram‐negative bacteria (Echerichia coli and Pseudomonas aeuroginosa ), and fungi (Aspergillus niger and Aspergillusfumigatus ) strains. The new compounds were characterized based on spectroscopic evidence. Among them compounds 10a , 10h , and 10i were showed promising activity when compared with standard drugs Ciprofloxacin and Miconazole.     

Synthesis of novel N‐alkyl/aryl‐N′‐(4‐arylthiazol‐2‐yl)‐N″‐xylosyl guanidines

The reaction of 2,3,4‐tri‐O‐acetyl‐β‐D‐xylopyranosyl isothiocyanate ( 1 ) and 2‐amino‐4‐arylthiazoles ( 2 ) gave xylosylthioureas 3 . These thiourea derivatives reacted with alkyl/aryl amine in the presence of HgCl₂ to give a new series of N‐alkyl/aryl‐N″‐(4‐arylthiazol‐2‐yl)‐N″‐xylosyl guanidines 4 . Some of the synthesized guanidines were screened for their biological activity. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:688–694, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20379     

Conversion of Some 2(3H)‐Furanones into Pyrrolinotriazine and Oxazolopyrimidine Derivatives

2(3H)‐Furanones 1 were utilized for the construction of pyrrolinotriazine and oxazolopyrimidine derivatives 4 and 9 . Thus, 1 reacted with glycine in ethanol at 70°C to give the acids 2 , which were cyclized into the pyrrolin‐5‐one derivatives 3 by the action of HCl/AcOH. The later compounds 3 were also obtained by refluxing the furanones 1 with glycine in glacial AcOH for 10 h. The carboxy functionality in 3 was used for the construction of a triazinone ring by treatment with thionyl chloride followed by refluxing the acid chloride with hydrazine in ethanol. The conversion of the furanones 1 into the oxazolopyrimidine derivatives 9 involved the following steps: (i) ring opening of the lactone ring with hydrazine hydrate to give the acid hydrazides 5 , (ii) conversion of the hydrazides 5 into the corresponding acyl azides 6 by action of NaNO2/AcOH, (iv) base‐catalyzed decomposition of the azides in the presence of glycine, (v) ring closure of the urea derivatives 7 into the pyrimidine derivatives 8 , and finally (vi) condensing 8 with benzaldehyde in the presence of NaOAc/AcOH mixture.     

Microwave‐Assisted Synthesis of β‐Lactams and Cyclo‐β‐dipeptides

Different cyclo‐β‐dipeptides were prepared from corresponding N‐substituted β‐alanine derivatives under mild conditions using PhPOCl₂ as activating agent in benzene and Et₃N as base. To evaluate β³‐substituent influence, the amino acids 7 – 26 were synthesized, and a β‐lactam formation reaction was carried out instead of cyclo‐β‐dipeptide formation. The crystal structures of three derivatives of cyclo‐β‐peptides and one β‐lactam are presented.