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Synthesis and biological significances of 1,3,4-thiadiazolines and related heterocyclic compounds
1st Heterocyclic Update
*Corresponding author. Tel.: +91 175 3046409; fax: +91 175 2283073 yusuf_sah04@yahoo.co.in (Mohamad Yusuf)
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Received: ,
Accepted: ,
This article was originally published by Elsevier and was migrated to Scientific Scholar after the change of Publisher.
Available online 4 March 2011
Peer review under responsibility of King Saud University.
Abstract
This review article describes the survey of literature regarding the variety of synthetic methods of 1,3,4-thiadiazoline and related compounds in the last seven years (2004–2010). The aim of the review is to find out different methods for the synthesis of thiadiazolines. These heterocyclics are majorly obtained from the cyclization reactions of thiosemicarbazone under the various conditions. From the literature studies it was found that major importance was given to their pharmaceutical significance i.e., regarding their biological activity against different fungal and bacterial strains.
Keywords
Thiadiazolines
Thiosemicarbazones
Bisthiadiazolines
Biological activity
Heterocyclic compounds
1 Introduction
Heterocyclic chemistry is an integral part of the chemical sciences and constitutes a considerable part of the modern researches that are occurring presently throughout the world. The chemistry of heterocyclic compounds is as logical as the chemistry of aliphatic or aromatic compounds. The study of heterocyclic systems is of great interest both from the theoretical and practical point of view. Heterocycles also play an important role in the design and discovery of new physiological/pharmacologically active compounds. Five membered aromatic systems having three heteroatoms at the symmetrical positions have been studied because of their interesting physiological properties (Hetzhein and Mockel, 1996). In the recent decades, the synthesis of substituted thiadiazolines (Wilkins, 2008; Shih and Wu, 2005; Ogurtsov et al., 2005) and related compounds has attracted considerable attention because these compounds constitute the structural frameworks of several naturally occurring alkanoids that show a wide range of pharmaceutical and industrial importance (Kornis, 1996). The technological uses of these compounds include dyes, optically active liquid crystals and photographic materials. Thiadiazolines, thiadiazoles and oxadiazolines possess a wide range of biological properties and they act as anthelmintics (Chen and Xiao, 2004; Xiong et al., 2002; Wang et al., 2003), antihypertensive (Oh et al., 2002), antitumour (Ilies et al., 2003; Masereel et al., 2002; Supuran and Scozzafava, 2000), analgesic, anticancer, anti-inflammatory and anti-bacterial (Amir and Shikha, 2004; Demirbas et al., 2004; Palaska et al., 2002; Holla et al., 2002; Awad and El Ashry, 1998), tyrosinase inhibitory activity (Khan et al., 2005). The macrocycles containing thiadiazoline and thiadiazole subunits are found to be interesting host guest complexation characteristics (Bradshaw et al., 1990) and also exhibit antibacterial activities (Collier et al., 2000; Elizabeth et al., 2003; Jian et al., 2008; Huang et al., 2002). Some synthetic routes for the synthesis of 1,2,3-thiadiazolines had been reported in literature (Vasiliy and Wim, 2004).
2 Discussion
The compounds 8 bearing two symmetrical 1,2,5-thiadiazole (Philipp et al., 2004) ligands had been synthesized (Scheme 1) in order to investigate the co-ordination catalyst for the co-polymerization of polar monomer (such as vinyl chloride and vinyl acetate) with ethylene. Here major investigations had been carried out on the complexes of transition metals with heterocyclic ligands 8.
The reaction of 3-benzoyl-5-perfluoroalkyl-1,2,4-oxadiazoles 12a–c with hydrazine had been initiated via the electrophilic C-5 addition of later on 1,2,4-oxadiazole ring (Buscemi et al., 2005), followed by ring opening and ring closure with enlargement to yield Z-oximes of 3-perfluoroalkyl-6-phenyl-2H-1,2,4-triazin-5-ones 17a–c as the major products of reaction under the mild experimental conditions (Scheme 4). In turn, the hydrazine can also attack upon the carbonyl carbon giving 4-perflouro-acylamino-5-phenyl-2H-1,2,3-triazoles 16a–c through the well-known Boulton–Katritzky rearrangement of the intermediate hydrazones (Schemes 3 and 4). Five membered oxadiazoles 9 react with hydrazine to provide six membered compound 10 (Scheme 2).
The researches are also carried out on the synthesis and biological activities of thiosemicarbazone 20 and thiadiazolines (Brousse et al., 2004) 21 (Scheme 5). It had been observed that thiosemicarbazone have stronger activity than thiadiazoline and thiosemicarbazone of aromatic ketones 22–25 and indanones 26–28 were associated with interesting antifungal activity. The terpenones based thiosemicarbazones 29–32 showed activity against the large numbers of bacteria than the aromatic derivatives 22–28.
Amir et al. (2004) have studied the synthesis and antibacterial/anti-inflammatory examinations of new trizoles 39a–b, thiadiazoles 40a–b, oxadiazoles 41a–b and 4-thiazolidinone derivatives 42a–b (Scheme 6). It was observed that in oxadiazole derivatives, the maximum activity (72.34%) was shown by compound 45a having a α-methyl-4-isobutyl benzyl group at position 2 but the replacement of this group by a simple phenyl group lead to a sharp decrease in the activity (22.34%). When phenyl group is replaced by mercapto group as in 43, 2′-hydroxy phenyl group as in 45d and 2′-acetoxyphenyl group as in 45e then activity was found to be increased. When these groups are further replaced by 2,4-dichlorophenyl as in 45c and amino groups as in 44 the activity was found to be decreased. On the basis of these results it was concluded that alkyl substituted phenyl rings were more preferable for the anti-inflammatory behaviours.
The reaction (Holla et al., 2004) of 2-chloropyridine-5-acetic hydrazide 49 with aroyl isothiocyanates 48a–e yielded 4-aroyl-1-(2-chloropyridine-5-acetyl)thiosemicarbazides 50a–e. The cyclization of later with conc. sulfuric acid and I2 + KI afforded 2-chloro-5-(5-aroylamino-1,3,4-thidiazol-2-yl-methyl)pyridines 51a–e and 2-chloro-5-(5-aroylamino-1,3,4-oxadiazol-2-yl-methyl)pyridines 52a–e, respectively as the final heterocyclic products (Scheme 7).
Some of new compounds like thiadiazolines 69 and 70, seleniumdiazolines 60b–63b and triazolino[4,3-a]pyrimidines 73 (Abdelhamid et al., 2004) have been obtained in the past starting from 3-aza-[2,4-dimethyl(1,3-thiazol-5-yl)-2-bromo-3-substituted-amino]prop-2-en-1-one under the reaction condition as shown in Schemes 8–12.
Shih and Wu (2005) have studied the reaction of thiosemicarbazones 89a–d with acetic anhydride 90a in the presence of ferric chloride to give 4-acetyl-2-phenylamino-5-(3-arylsydnon-4-yl)-4,5-dihydro-[1,3,4]thiadiazoles 91a–d and 4-acetyl-2-(N-phenylacetamido)-5-(3-arylsydnon-4-yl)-4,5-dihydro[1,3,4]thiadiazoles 92a–d (Scheme 13). However under similar conditions thiosemicarbazones 89e–h produced only 4-acetyl-2-acetamido-5-(3-arylsydnon-4-yl) 4,5-dihydro-[1,3,4]thiadiazoles 92e–h in high yield (Scheme 14). The sydnonyl-substituted thiadiazole derivatives 93a–h were also prepared successfully by the cyclization of 3-aryl-4-formylsydnone thiosemicarbazone 89a–h in the presence of ferric chloride (Scheme 15). The cyclization reaction of thiosemicarbazones 89a–d could occur easily than thiosemicarbazones 89e–h.
Ogurtsov et al. (2005) prepared 1,3,4-thiadiazolines 97 of 1,2-dithiole-3-thiones (Schemes 16–18). The thiocarbonyl group of 4,5-dichloro-1,2-dithiole-3-thione reacts as a dipolarophile towards dicarbonyl nitrile imines by 1,3-dipolar cycloaddition followed by opening of the dithiole ring with loss of sulfur to give 5-methylene-1,3,4-thiadiazolines. This reaction together with nucleophilic displacement of the selectively reactive 5-chloro group provides a rapid access to stable 5-methylene-1,3,4-thiadiazolines. Here compound 97aa was obtained by 1,3-dipolar cycloaddition followed by the loss of sulfur, but it was too unstable to be isolated. The reaction of 95a and 94a with triethylamine in benzene solvent at room temperature followed by addition of phenol or thiophenol led to the formation of thiadiazolines 97ab and 97bc, (X = O and S) in low yields.
The reactions (Caram et al., 2006) of n-butylamine, 2-aminoethanol, diethylamine and phenylhydrazine with 98a were studied by cyclic voltammetry. The course of the reactions was dependent on the nucleophile-substrate combination: Et2NH added to 98a, forming the corresponding thiadiazolines in an equilibrium mono addition reaction. The equilibrium constants were evaluated and compared. With primary amines and PhN2H3, the nucleophile added to both C⚌N double bonds of 98a and displayed the sulfamide moiety. BuNH2 and H2N(CH2)2OH reacted with 98a to give bis-imines, while 98a with PhN2H3 gave the α-bis-hydrazone (Scheme 19). The configuration of benzil-bis(ethanolamine) and benzilosazone were determined by single X-ray diffraction analysis as Z, Z.
The synthesis of new 1,3,4-thiadiazole (Schenone et al., 2006) 102 derivatives endowed with analgesic and anti-inflammatory activities have been reported. Two series of N-[5-oxo-4-(arylsulfonyl)-4,5-dihydro-1,3,4-thiadiazol-2-yl]-amides 102a–t (Scheme 20) were synthesized and tested in vivo for their analgesic and anti-inflammatory activities. All the new compounds were found to exhibit good analgesic action and some compounds also showed fair anti-inflammatory activity in the carrageenan rat paw oedema test. Ulcerogenic and irritative action on the gastrointestinal mucose, in comparison with indomethacin was observed to be low.
Zaki et al. (2006) have prepared 2,3-dihydro-1,3,4-thiadiazoles 112–115 and 120, in good yields from the reactions of hydrazonoyl halides with alkyl carbodithioates, pyrimidine-2-thione and substituted prop-2-ene-1-one, respectively (Schemes 21–23). Some of these compounds were also tested against the bacteria and fungi strains.
Mazoir et al. (2006) synthesized some steroidal based spirocyclic thiadiazolines under the ordinary conditions as shown in Scheme 24.
The heterocyclic derivatives (Mithun and Holla, 2007) 7-(substituted aryl/aryloxy methyl-3-(4-methylthiobenzyl)-4H-1,3,4-thiadiazolo [2,3-c]-1,2,4-triazin-4-ones 130a–d and 131a–d were prepared by reacting 4-amino-6-(4-methylthiobenzyl)-3-mercapto-1,2,4-triazin-5(4H)-one 129 with substituted benzoic acids/aryloxy acetic acids in the presence of phosphorus oxychloride. 4-Amino-6-(4-methylthiobenzyl)-3-mercapto-1,2,4-triazin-5(4H)-one 129 was prepared by reacting 4-(4-methylthiobenzylidene)-2-methyl-oxazol-5-one(3) with thiocarbohydrazide 128 by refluxing in aq. EtOH (Scheme 25). The antibacterial and antifungal activities were carried out for 130a–d and 131a–d and all the tested compounds were possessing moderate activity for both microbes.
The treatment of 132 with carbon disulfide in the presence of potassium hydroxide resulted in the formation of 1,3,4-thiadiazole (Mahmoud et al., 2007) 135 (Scheme 26).
The literature (Zareef et al., 2007) also describes the synthesis of a series of novel chiral and achiral N-[1-(1,3,4-oxadiazol-2ylthiol alkyl]-4-methyl/chloro/methoxy benzenesulfonamides 140a–l (Schemes 27 and 28). These compounds were prepared by the reaction of 4-[4-methyl, chloro, methoxyphenylsulfonamido) alkyl carboxylic acid hydrazides 139a–l with CS2 and KOH. Another series of new secondary benzenesulfonamides 145a–j and bis-benzenesulfonamides 146a–j have also been synthesized by a new approach using Et3N and dimethylaminopyridine. The compounds 136a–d were converted into their corresponding sulfonamides 137a–l. Esterification of 137a–l with ethanol in an acidic medium afforded esters 138a–d and reaction of later with 80% hydrazine hydrate furnished hydrazides 139a–l in good yields. The products 140a–l were then prepared by the reaction of hydrazides 139a–l. The hydrazides 141a–e were converted into 142a–e by treatment with 4-nitrobenzoylchloride in dry MeCN. Compounds 142a–e were subjected to dehydrative cyclization in the presence of thionyl chloride to give 143a–e. The reduction of 143a–e with Pd/C and hydrazine hydrate produced 144a–e in good yields. The treatment of 144a–e with Et3N and dimethylaminopyridine furnished the sulfonamides 145a–e and 146a–e (Scheme 28). The prepared compounds were also checked for their anti-HIV activity.
Twenty one new thiophene substituted 1,2,4-oxadiazol-5(4H)-ones (Durust et al., 2007) 152a–g, 1,2,4-oxadiazol-5(4H)-thiones 154a–g and 1,2,4-oxadiazin-5(6H)-ones 160a–g were synthesized by the reaction of thiophene ring substituted amidoximes with ethyl chloroformate, thiophosgene and chloroacetylchlorine, respectively according to the protocol as described in Schemes 29–32.
Ying et al. (2007) have investigated the synthesis of a series of flavanoid based thiadiazoline 170 and 171. These heterocycles were synthesized by the cyclization of the corresponding 2-arylchroman-4-one-arylhydrazones 166 and 167 with SOCl2 followed by treatment with alcohol (Schemes 33 and 34). The resulting compounds 170 and 171 were also examined for their antiproliferative activity in vitro against six human tumour cell lines and the derivative 171a was found to have higher inhibitory effect upon the growth of tumour cell.
The spirocyclic oxadiazole (Islam and Mohsin, 2007) 179 were synthesized successfully starting from p-chloroaniline through the sequence of reactions as shown in Scheme 35.
The cyclization (Li et al., 2007) reactions of 3-aryl-4-amino-5-mercapto-1,2,4-triazoles 181a–o with hexanedioic acid in the presence of POCl3 and Bu4N+I− as a catalyst provided 1,4-bis(3-aryl)-1,2,4-triazolo[3,4-b]–[1,3,4]thiadiazole-6-yl]butanes 182a–o (Scheme 36). The compounds 182a–o were screened for their anti-bacterial and compounds 182d, 182n and 182o showed better antibacterial activity.
The inhibition activity on carbonic anhydrase I of some substituted thiadiazole and thiadiazoline-disulfonamides (Bolboala, and Jantschi, 2007) have been studied. The structure activity relationships based upon an original molecular descriptors family method has been developed and applied on a sample of substituted 1,3,4-thiadiazole and 1,3,4-thiadiazoline-disulfonamides. Forty compounds were studied for their inhibition activity on carbonic anhydrase I. The results revealed that the molecular descriptions family on structure activity relationships is a useful approach in the characterization of inhibition activity on carbonic anhydrase I of studied substituted 1,3,4-thiadiazole and 1,3,4-thiadiazoline-disulfonamides.
In order to investigate a better antimicrobial agent, 1,3,4-thiadiazoles (Banday and Rauf, 2008) 186a–d bearing long alkenyl and hydroxyl-alkenyl chain have been synthesized (Scheme 37) and their antibacterial activity has also been examined.
Abdelhamid et al. (2008) have prepared 1,3,4-thiadiazolines containing a chromone moiety and 5-{1-[4-substituted-5-phenyldiazenyl)(1,3-thiazol-2-yl]-5-phenyl-2-pyrazoline-3-yl)}-4-methoxybenzo[b]-furan-6-ol. These compounds were prepared from the reaction of hydrazonoyl halide and alkyl carbodithioates and 5-[1-aminothiomethoxy)-5-phenyl-2-pyrazolin-3-yl)]-4-methoxybenzo[b]-furan-6-ol, respectively (Schemes 38–41).
Er et al. (2008) have investigated the cyclization reactions of new tetra-thiosemicarbazone. The tetra-aldehyde and ketone derivatives 205a–d which were used in these syntheses were obtained via the reaction of ethane-1,1,2,2,tetra-yl-tetra-methylene-tetra-bromide with aldehydes and ketones. The reactions of tetra-aldehydes and ketone derivatives 205a–d with thiosemicarbazite and 4-methyl thiosemicarbazite led to the formation of 206a–h. In the same way, tetra-4-methyl-5-ethoxycarbonyl 1-2,3-dihydro-1,3-thiazoles 207a–h were synthesized via the reaction of tetra-thiosemicarbazone compounds 206a–h with ethyl-2-chloroacetoacetate. Finally compounds 206a–h were reacted with acetic-anhydride under refluxing to yield tetra-2-acetyl-amino-4-acetyl-4,5-dihydro-1,3,4-thiodiazol compounds 207a–d and 208a–d (Scheme 42).
The interaction of α,β-unsaturated ketones of furan series (Anis’Kov et al., 2009) with thiosemicarbazide under basic catalysis condition led to 3-furyl-2-thio-carbamoylpyrazolines and the intramolecular cyclization of thiosemicarbazones under conditions of acid activation of sulfurous nucleophile provided spirocyclic furylmethylene 1,3,4-thiadiazoline. These heterocycles are of potential biological activity and can be used in medicines.
The heterocyclization of 210a–d under the acylation condition proceeded regioselectively to give 5-furfurylidene-1,3,4-thiadiazoline including spirocyclic one. The use of basic catalysis in these reactions allows one to carry out region directed synthesis of N-thiocarbamoyl pyrazolines (Scheme 43).
A series of novel 2-(1-substituted-1,11-undecylidene)-5-aryl-imino-Δ-1,3,4 thiadiazolins (Jin et al., 2009) 218 had been synthesized and their solubility in polar and non polar solvents was significantly improved owing to the introduction of ethyl or methylthio group at cyclodecyl ring as compared with parent compounds [1,2-(1,11-undecylidene)-5-aryl imines-Δ-1,3,4-thiadiazolines] (Scheme 44). However their fungicidal activity against Rhizoctonia Solanu is less than that of parent compounds.
The [3+2] cycloaddition reaction (Jayashankar et al., 2009) of nitrile oxide with allyl alcohol followed by intramolecular 1,3-dipolar cycloaddition reaction of nitrile imine with carbonyl group could led to the formation of novel ether linked bis(heterocycles) (Scheme 45). These bisheterocycles were also tested for anti-inflammatory and analgesic activities and 225g exhibited highest activity among the tested products 225a–e.
The reaction of trans-1,4-dichloro-2-butene 226 with phenol afforded (E)-1,4-bis(aryloxy)-2-butene Er et al., 2009 228a–d which were converted into bis-thiosemicarbazones 229a–h by reacting with thiosemicarbazide and 4-methyl thiosemicarbazide, respectively. Similarly, 4-methyl-5-ethoxycarbonyl-2,3-dihydro-1,3-thiazoles 231a–h were synthesized via the reaction of bis-thiosemicarbazones 229a–h with ethyl 2-chloroacetoacetate. trans-1,4-Dithiocyanato-2-butene 230 was obtained from the reaction of KSCN and trans-1,4-dichoro-2-butene 226. Furthermore, the bis-2-amino-1,3,4-thiadiazoles 232k and I were realized from the reaction of trans-1,4-dithiocyanato-2-butene 230 with thiosemicarbazide and 4-methyl thiosemicarbazide, respectively (Scheme 46). Finally the microbial activities of all the compounds 231a–h were also determined.
The synthesis of some new heterocyclic compounds (Pawar et al., 2009) has been reported containing spiro-benzopyrans, thiadiazoles, selenadiazoles and thiadiazolines as the subunits (Scheme 47). The anti-microbial and anti-fungal analyses of the heterocycles have been carried out.
The condensation reaction of 4-amino-5-(aroyl)-4H-1,2,4-triazole-3-thiols 240a–b or 2-amino-5-mercapto-1,3,4-thiadiazole with bis-aldehydes 239a–c provided bis-schiff bases 241a–d and 245a–c (Foroughifar et al., 2009) which were further treated with dibromoalkanes to afford the new macrocycles 243a–f and 247a–d, respectively (Schemes 48 and 49).
Recently, multistep synthesis of the steroidal based thiadiazolone derivatives (Khan and Yusuf, 2009) has been reported. The target compounds 254–256 were obtained from the cyclization of thiosemicarbazones 251–253 with bromoethylacetate in dioxane medium. The later were prepared from the reaction of steroidal ketones 248c–250c with thiosemicarbazones (Scheme 50). The antibacterial analysis of the compounds 254–256 showed that steroidal thiozolidinone derivatives are better in inhibiting the growth as compared to steroidal thiosemicarbazones.
El-Sayed et al. (2009) have investigated the synthesis of a series of new disubstituted 2,5-thiazolidinone derivatives 260a–d, 262a–d and 264a–d (Scheme 51). The antimicrobial examination of these compounds has also been carried out against gram positive and gram negative bacteria strains and actinomycetes.
The 1,3,4-thiadiazoline (Umamatheswari and Kabilan, 2009) 267 had been obtained starting from 3-methyl-2,6-diphenyltetrahydrpopyran-4-one 265 which was treated with thiosemicarbazide to give 266. The cyclization later with Ac2O resulted in the formation of final product (Scheme 52). These results showed that the title compounds exist in chair conformation with equatorial orientations of phenyl group at C-2, C-6 methyl group at C-3 carbons and N-acetyl group of thiadiazoline moiety.
Some halogenated thiadiazoles and trizoles (Radhavane et al., 2010) were synthesized initially starting from acid hydrazine 268 under the conventional and ultra sound irradiation method (Scheme 53). These heterocyclic compounds 270 and 271 were also examined for their anti-microbial, antiviral and anti-oxidant activities.
A reaction of alkenoic acid hydrazides 272a–d with phenylisocyanate and phenylthiocyanate yielded semicarbazides 273a–d and thiosemicabazide (Farshori et al., 2010) 275a–d, respectively, which were further refluxed with POCl3 and Ac2O to provide 1,3,4-oxadiazoles 274a–d and thiadiazoles 276a–d, respectively (Schemes 54 and 55). The anti-bacterial and anti-fungal analyses of the synthesized compounds have also been carried out.
A series of new 2-imino-5-[(Z)-1-(4-methylphenyl)methylidene]-3-[5-(2-oxo-2H-3-chromenyl)-1,3-oxazol-2-yl]-1,3-thiazolan-4-ones (Reddy et al., 2010) 281a–j have been synthesized (Scheme 56) and assayed for their antibacterial activity. Among the screened products, the compounds 281d, 281e, 281f, 281g and 281j exhibited better activity as compared to the standard drug and emerged as potential derivatives for further researches.
Kabilan and co-workers have investigated the synthesis of some novel 2,4-[diaryl-3-azabicyclo[3.3.1]nonan-9-yl]-5-spiro-4-acetyl-2-(acetylamino)-Δ-1,3,4-thiadiazolines (Rani et al., 2010) derivatives 285a–h. These compounds were obtained by the cyclization of 2,4-[diaryl-3-azabicyclo[3.3.1]nonan-9-one thiosemicarbazones 284a–h under acetic anhydride medium (Scheme 57).
The macrocyclic compounds containing heterocyclic subunits have attracted the attention of synthetic chemists as these molecules can act as ligand in the asymmetric catalysis (Cho et al., 2010) and as a host molecule for the incorporation of metal ions. Nam Sook Cho and et al have developed the synthesis of novel macrocycles 289a–f containing 2-imino-5-mercapto-3H-1,3,4-thiadiazoline unit linked at 3 and 5 positions through the ethyl, butyl and m-xylene moiety (Scheme 58). The X-ray diffraction studies could become helpful to ascertain the structure of these compounds.
The significant biological properties (Hossain et al., 2010) (like anti-oxidant, anti-microbial and anti-cancer) associated to the Isatins has promoted the synthesis and biological evaluation of the new heterocyclic compounds 293a–c, 294d–f and 296g–j. These compounds were obtained by the synthetic routes as shown in Scheme 59.
Heng-Shan Dong et al. have synthesized N-[4-acetyl-4,5dihydro-5-(1-aryl-5-methyl-1H-1,2,3-triazol-4-yl)-5-methyl-1,3,4-thiadiazol-2-yl]acetamide (Wang et al., 2010) derivatives 299a–j according to the protocol as described in Scheme 60.
Recently, new acridone based 1,3,4-oxadiazoles (Salimon et al., 2010) 305 have been obtained starting from the reaction of 2-chlorobenzoic acid with 4-aminobenzoic acid (Scheme 61). These compounds are also associated with the significant anti-bacterial and anti-fungal activities.
A novel series of pyridyl substituted oxadiazole (Shirote and Bhatia, 2011) 309a–f have been synthesized through the cyclization of carbonyl hydrazone under the excess of acetic anhydride and subsequent condensation with various aromatic amines (Scheme 62). These compounds were also screened for their goat pulmonary vein relaxant activity and compound PSMB9 was found to be the most active derivative exhibiting 83.33% relaxation.
Recently, synthesis and anti-microbial analysis of some new 1,2,4-thiadiazolinediones (Alagawadi and Alegaon, 2011) 314a–g and 318a–g (Schemes 63 and 64) have been reported by Shankar G. Alegaon and co-workers. These heterocycles exhibited high to moderate biological behaviour against the tested bacteria and fungi strains.
Recently, synthesis of new heterocyclic compounds (Duan et al., 2010) 322a–f has been carried out through the multi step reactions as shown in Scheme 65. The herbicidal activities of these compounds have also been examined against a variety of weeds. This study showed that most of the synthesized compounds had moderate inhibitory activities and selectivities against root and stalk of monocotyledon and dicotyledon plants. The chiral compounds showed improved herbicidal activities to some extent over their racemic counterparts against a variety of tested weeds.
The bisthiadiazolines (Yusuf and Jain, 2012) 325a–h built around the alkyl chains of varying lengths have been synthesized in good yields by refluxing bisthiosemicarbazones 324a–h in acetic anhydride. The reactions of bisaldehydes 323a–h with thiosemicarbazide in alcoholic medium provided 324a–h. The formation and stereochemical features of the bisthiadiazolines 325a–h were found to be independent of the internal spacer length (Scheme 66).
5-(4-Chlorophenyl amino)-2-mercapto-1,3,4-thiadiazole (Sah et al., 2010) was refluxed with formaldehyde and ammonium chloride in ethanol to yield Mannich base 5-(4-chloro phenyl amino)-3-aminomethyl-2-mercapto-1,3,4-thiadiazole 326. Esterification of later with 4-chloro-(2,6-dinitrophenoxy)-ethyl acetate 327 under anhydrous conditions gave the intermediate 328 which upon subsequent hydrazinolysis with hydrazine hydrate gave the corresponding hydrazide 3-amino methyl-5-(4-chloro phenyl amino)-2-mercapto-4′-(2′,6′-dinitro phenoxy)-acetyl hydrazide 329. The hydrazide was converted into the Schiff bases 330a–b by reacting with 2-chlorobenzaldehyde and 3-methoxy-4-hydroxy-benzaldehyde in presence of methanol containing 2–3 drops of acetic acid. The diazotization of 330a–b with aromatic amines, sulfanilic acid and sulfur drugs gave the formazans 331a–g, respectively (Scheme 67).
Acknowledgement
Authors are highly thankful toDST, New Delhi (SERC, Fast Track Scheme No. SR/FT/CS-041/2010) for providing the financial support for this work.
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