CHAPTER-I INTRODUCTION TO THE CHEMISTRY OF BENZIMIDAZOLES. In the past decades, the literature seems to brim over with

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1 CAPTE-I ITDUCTI T TE CEMISTY F BEZIMIDAZLES General:- In the past decades, the literature seems to brim over with research work on nitrogen containing heterocycles, as they are present in nucleic acids, vitamins, proteins and biologically important molecular systems. Benzimidazole is one such leading nitrogen heterocycles containing potential pharmacological properties. The discovery of 5, 6-dimethyl-1-(α-D-ribofuranosyl) benzimidazole 1 is fundamental structure of the vitamin-b 12. When a benzene ring (I) is fused to an imidazole ring (II) through its 4, 5-bond, a benzimidazole ring (III) is formed. (I) (II) 1 2 (III) (III) The two nitrogens present in the imidazole ring are different from one another in their nature, and makes the properties of the ring system diverse in character. The hydrogen attached to the nitrogen in tautomerism with the other nitrogen. 12

2 (III) (IIIa) Due to this tautomerism, certain benzimidazole derivatives, which appear at first as isomers, are in reality tautomers. 3 C C (IV) (IVa) To prevent any confusion between the two tautomers, both the designating structures are written with the second one in parentheses, e.g., 5(6)-methylbenzimidazole, and 4(7)- methylbenzimidzole. 5 6 C 3 3 C (V) (Va) When a group attached to nitrogen in the 1-position is larger than hydrogen, such tautomerism is prevented and isomeric forms exist. Thus, 1, 5-dimethylbenzimidazole (VI) and 1, 6-dimethylbenzimidazole (VII) exist as distinct, isomeric compounds. 13

3 3 C C 3 (VI) C C (VII) IMPTACE F BEZIMIDAZLE IG SYSTEM:- A large number of benzimidazole derivatives find use as pharmaceuticals. Some of the commercially important benzimidazole derivatives, are shown in Table-1. S. 0 Structure Importance C 3 1 Antihistam F Astemizole inic C 2 C 3 Bezitramide Analgesic 14

4 Antihypert 3 C C 3 Candesartan ensive Cl Antiemetic 4 Domperidone C 3 5 C 3 Emedastine Antiallegric 6 C 3 Irtemazole Uricosuric agent 7 S C 3 CF 3 Lansoprazole Antiulcer 15

5 8 Cl F Milenperone Antipsycho tic 9 Cl Cl 3 C C 3 Antiviral Maribavir 10 3 C S C 3 C 3 C 3 meprazole Antiulcer 11 C 3 C 3 Pimobendan Cardiotoni c 12 3 C C C 3 Antielmenti Parbendazole c 13 S C 3 C 3 Antiulcer abeprazole 16

6 SYTESIS F BEZIMIDAZLES:- The reviews and articles covering the chemistry of both imidazoles and benzimidazoles have been published earlier. Therefore, only a brief account is given here. Benzimidazoles may be synthesized from: 1. o-phenylenediamines 2. o-(-acylamino and aroylamino)arylamines and nitroamines and nitroarenes. 3. o-itroarylamines and o-dinitroarenes 4. o-substituted--benzlideneanilines 5. Amidines and 6. ther heterocyclic compounds. 1) From o-phenylenediamines: o-phenylenediamines react with (a) carboxylic acids and their derivatives, (b) imino-ethers (c) carbonyl compounds and (d) nitriles to yield differently substituted benzimidazoles. a) By reaction with carboxylic acids and their derivatives: o-phenylenediamine (VIII) when condensed with carboxylic acids under a variety of conditions gave 2- substitutedbenzimidazoles in good yields. 17

7 2 2 + C (VIII) (IX) (III) Scheme-1.1 Benzimidazoles were syntheized from o-phenylenediamines and aliphatic acids Phillips developed a satisfactory method for the preparation of 2-alkylbenzimidazoles (X, =C3). EMBED ChemDraw.Document C- 4 Cl (VIII) (XI) (X) (=C 3 ) Scheme-1.2 The role of hydrochloric acid 37 is to activate carboxyl group by addition of a proton to oxygen, forming carbonium ion. The reaction mechanism involves carbonium ion intermediate. 2 C C 2 2 C (X) (=C 3 ) Scheme

8 This procedure however, fails to give any respectable yields of 2- arylbenzimidazoles (XIII) 37 with aromatic acids. Yields of 2- arylbenzimidazoles were increased with o-phenylenediamines in a sealed tube at o C. Polyphosphoric acid or polyphosphate 42 esters were used as condensing agents for o-phenylenediamines and aromatic acids for good yields C- PPA or PPE (VIII) (XII) (XIII) Scheme-1.4 The procedures described above were utilized in recent years for the preparation of benzimidazoles possessing thiazolyl, thiadiazolyl substituents in 2 nd - position The other derivatives include 1-aryl- 5-amino 45, 2-trifluoromethyl 46, 2,6-bis(trifluoromethyl)-4-nitro 47, 2-βmercaptoethyl 48, 2-(1-aminoalkyl) 49, 2-(p-iodobenzyl) and 2-(piodostryl) 50 are benzimidazole derivatives. The reaction between o-diamine and an ester was first investigated by Von iemantowski 51 who prepared (XVI) by condensing equimolar amounts of XIIII and XV at 225 o C in sealed tube for 3hrs. 3 C (XIIII) 2.2Cl 2 + C C 2 5 (XV) 225 o C 3 C (XVI) C 3 Scheme

9 Landenburg 52 first prepared XVI by refluxing XVII in glacial acetic acid. 3 C (XVII) C (XI) 3 C (XVI) (=C 3 ) Scheme -1.6 X was obtained by prolonged treatment of VIII with XVIII whereas treatment for a short time yielded only XIX 53 Wagner 54 reported improved yields X from VIII and XVIII by using dilute Cl. CC 3 CC (C 3 C) 2 (XIX) (VIII) (XVIII) (X) C 3 Scheme -1.7 XX when reacted with XVII in benzene solution yields XVI if the reaction is done without cooling and XXI when the reaction is cooled C CC 3 3 C 2 3 C C 3 CCl + CC 3 2 (XXI) (XX) (XVII) (XVI) C 3 Scheme

10 iementowski synthesized IV by heating XIV with the corresponding amides. 56 Bisbenzimidazoles (XXV) were synthesized by heating o-diamines or their salts with aliphatic acid amides XXIV in solvents like ethylene glycol and glycerol 57 having high boiling points. 2.2Cl + (C 2 ) n (C 2 ) 2 X 2 (C 2 ) n (XIV) (XXIV) (XXV) X Scheme -1.9 b) By reaction with imino-ethers (Imidates): o - phenylenediamine on reaction with imino ether in dil.acidic medium led to the formation of benzimidazole in high yields. The drawback in the Phillips procedure is that diamine competes for the proton of the acid. E.g. XXVIII was synthesized in 95% yield by reacting o-phenylenediamine hydrochloride (XXVI) with trichloroacetimidate (XXVII) at room temperature Cl + 3 C C CCl 3 T CCl 3 (XXVI) (XXVII) (XXVIII) Scheme The scope of imidate procedure has been assessed by Acheson and King

11 c) By reaction with carbonyl compounds: ao and atnam, 69 and by Smith and o 70 independently reviewed the reaction between o-diamines and aldehydes as a method to synthesize benzimidazoles. o-phenylenediamine when condensed with aldehydes resulting various 2-substitutedbenzimidazoles in the presence of oxidising agents such as cupric acetate (Weidenhagen procedure), 71 mercuric oxide (for 2-CMe), 72 chloranil (for 2- furyl), 73 lead tetra acetate, 74 manganese dioxide, 75 ickel peroxide 76 and nitrobenzene C- (VIII) (XII) (XIII) Scheme The reaction between o-arylenediamines with formaldehyde gives rise to 1-methylbenzimidazoles, and this type of procedures has been studied in detail. 81 Depending on the nature of the aldehyde and the molar proportions in the reaction, o-phenylenediamine when condensed with aromatic aldehydes results in the formation monoanils and dianils in some cases 69. Products containing cyclic structures such as XIII, 1:1 product and XXXI, 1:2 product are formed in varying proportions in acetic acid at room temparature. 22

12 C 2 (XXIX) (XIII) 2 2 (VIII) C C C 2 (XXX) (XXXI) Scheme The monoanils (XXIX) which are prepared separately are converted to 2-substitutedbenzimidazoles by treating with dehydrogenating agents C + C- 2 2 (VIII) (XXII) (XXIX) (XIII) Scheme Both under acidic as well as thermal conditions , dianils (XXX) can also be cyclised to 1, 2-disubstitutedbenzimidazoles. C C C 2 (XXX) (XXXI) Scheme

13 ao and Co-Workers, 88 studied the isolation, of XXXII (1:3 product) in the condensation of o-phenylenediamine with simple o- chloro and m-nitrobenzimidazoles in acetic acid at room temparature (VIII) (XXII) (XIII) (XXXI) C C 2 - C 2 - (XXXII) Scheme The monoanils have been shown 89 to exist in taotomeric form with the corresponding dihydrobenzimidazole by M spectroscopy. C 2 (XXIX) (XXXIII) Scheme These dihydro derivatives could not be isolated in a free state in the reaction of o-phenylenediamine with aromatic aldehydes. They were, however, isolated 90 in pure form in the reactions of 2,3- pyridinediamine with aromatic aldehydes. Furthermore, the structures of the monoanils obtained from the reaction between 2,3- pyridinediamines and aromatic aldehydes has also been established 91 unequivocally by X-ray crystallographic methods. 24

14 ii) By reaction with ketones: IT has been reported that -phenylenediamine when condensed with ketones gave 2, 2-disubstitutedbenzimidazoles (XVI) which decompose under the influence of heat to a 2- substitutedbenzimidazole and a hydrocarbon. (VIII) 2 + C 2 (XXXV) (XXXIV) 1 1 > (X) = C 3 Scheme d) By reaction with nitriles: XIV when heated with itriles at 200 o C gave X. This reaction has been studied by ollies and Wagner 95 and they proposed the following mechanism for the reaction. 2.2Cl 2 (XIV) + C (XXXVI) (VIII) 2 + -C.Cl 2 2 C 3 Cl (X) + 4Cl =C 3 Scheme Using this procedure 2- substituted benzimidazoles have been synthesized. 25

15 2) From o-(-acylamino and -aroylamino)arylamines and nitroarenes: The o-phyenylenediamine can be synthesized insitu from the appropriate o-nitroarylamine by using a variety of reducing agents such as Sn/Ac, 108 a 2S 2 4, 109 2/PD/C, 110 aney i, 111 SnCl 2/Cl, 112 Fe/Ac, 113 Zn dust/ac, 32 a 2S 114 (sod.sulphide) etc. 1 C 2 aq. Cl or 2 eat 1 1 eductant C (XXXVII) (III) (XXXVIII) 1, 2 = Scheme Thus, Bisbenzimidazoles and releated derivatives were synthesized by the cyclisation of mono-aryl-o-phenylenediamine. Ph X Ph Ph Ph Ph Ph X = p- and m-phenylene, 4,4 1 -C 6 4 -C 6 4 etc (XL) (XXXiX) Ph Ph S Ph Ph (XIL) Scheme

16 3) From o-nitroarylamines and o-dinitroarenes: Benzimidazoles are synthesized in a single step from an o- nitroarylamine or an o-dinitroarene by using various reducing agents. These procedures have got commercial importance since reasonable yields were obtained. A secondary reaction occurs and converts the 2- alkylbenzimidazole into 1, 2-dialkylbenzimidazoles, 122 when o- nitroanilines are used in thermolysis. (C)C 2 / aney i 2 C 2 (XIIL) (XIIIL) (XIVL) C Scheme In thermally uncatalysed cyclisation reactions benzimidazoles were obtained from -substituted-o-nitroaniline (XVL) derivatives. 124 C 2 eat in sand 2 (XVL) (XIII) Scheme The acid catalysed cyclisation of XVIL to -aminobenzimidazoles (XVIIL) has been reported

17 aq. Cl / eat 2 (XVIL) (XVIIL) Scheme ) From o-substituted -benzimideneanilines: omatic nitro compounds on reduction by triethylphosphite and related reagents has been widely used as a simple, route to a variety of nitrogen containing heterocycles. 127 XVIIIL derivatives are converted 128 into 2-phenylbenzimidazoles by using triethylphosphite and similar reducing reagents and the yields are slightly higher than those obtained by the use of classical weidenhagen aldehyde method. 2 (XVIIIL) C Ph (Et) 3 P/ t-buc 6 5 reflux (XIII) Ph Scheme Good yields of benzimidzoles were obtained by heating XVIIIL in 1, 2-dichlorobenzene 129 or dimethylformamide (XVIIIL) C Ph (XIII) Ph Scheme

18 5) From amidines: Generally, benzimidazoles are synthesized from o- phenylenediamine and its derivatives. The reactions were carried out under mild conditions using benzenesulphonyl chloride in pyridine or in triethylamine resulting good yields. Consequently, it has been shown that such products can be obtained from the parent amidines by oxidation under basic conditions. 132 PhS2Cl / Et 3 or Pyridine <10 o C (XIXL) (X) =C 3 Scheme ) From heterocyclic compounds: Benzimidazole derivatives (LI) were extracted 133 from reductive cyclisation of o-benzoquinonedibenzimide (L) by triphenylphosphine. CPh CPh (L) + Ph 3 P CPh Ph (LI) + Ph 3 P Scheme Thus, in the absence of a substituent, LII is converted into benzimidazole in poor yield together with trace quantities of LIII; LIV are converted in very good yield into LV and LIV by opening of the - 29

19 -bond and migration of the hydrogen from C 3 to i to give 2- alkylaminobenzonitriles. 134 hv + C 2 (LII) (III) (27%) (LIII) (Trace) (LIV) hv (LV) (73-96 for =alkyl, aralkyl, ) (LV) hv (LIII) C 2 Scheme ecent work for the synthesis of benzimidazoles derivatives:- Singh et. al. reported 136 that bisbenzimidazole derivaties were obtained by coupling of aromatic orthodiamines with aromatic and heterocyclic aldehydes by oxidation. 30

20 3 C II 2 Fe III-FeII + C- 2 3 C (XVII) (XXII) (LIX) 2 C (LX) PCC / C 2 Cl 2 C (LXI) r 2 2 (LXII) r (LXIII) Lu et al reported 137 the synthesis 2-substitutedbenzimidazoles by using polyphosphoric acid as a catalyst from organic acids under micro-wave irradiation. 2 PPA / MW + C- 2 (VII) (XXII) (XXIII) Scheme Substituted benzimidazoles were synthesized by using ytterbium triflate as a catalyst C- Yb (Tf) 3 (XXIII) (XXII) (LIX) =C 3 Scheme Taylor et al. reported 140 the synthesis of 2-substitutedbenzimidazoles in good yields directly in the presence of manganesedioxide and molecular sieves in a one-pot method. 31

21 C 3 + -C 2-2 Mn 2 Sieves 18hr C 3 (LXIV) (LXV) (LXVI) Scheme Perumal et al. reported 141 the synthesis of 2-aryl-1-arylmethyl- 1-1,3-benzimidazoles in the presence of montmorillonite k-10 from o-phenylenediamine and aromatic aldehydes in the absence of solvent under microwave conditions C- K-10 Clay MWI (VIII) (XXII) (XXXI) Scheme Salehi et. al. reported 145 selective synthesis of 2-aryl-1- arylmethyl-1-1, 3 benzimidazoles in the presence of silica and sulphuric acid in water or ethanol C- Silica sulfuric acid water (VIII) (XXII) (XXXI) =C 3 Scheme SPECTAL PPETIES F BEZIMIDAZLES:- I spectra of benzimidazole were studied in detail by abiger and Morgan. 147 Turchin 148 studied in detail, M spectrum of the benzimidazole in the acid solutions, which was found to give the 32

22 following chemical shift values (ppm) in CD 3 and TMS as internal standard , 7 5, C spectrum of the benzimidazoles 149 was found to give the following chemical shift values in CD , 6 8, The mass spectral fragmentation of the benzimidzoles was observed by Bowie 150 from which it appears that the fragmentation pathways of benzimidazoles are similar to that of imidazole. The spectrum of benzimidazole indicates a sequential loss of two molecules of hydrogen cyanide from the molecular ion. C 2 - C 6 5 (m/e 91) -C C 6 5 (m/e 92) 33

23 CEMICAL PPETIES F TE BEZIMIDAZLES:- 1) eactions with electrophillic reagents:- i) Electrophilic aromatic substitution does not occur easily in the imidazole ring of benzimidazoles. Benzimidazole on treatment with Cl 2 gives 4, 5, 6-trichlorobenzimidazole. 152 I 2 / a (III) (LXVII) I (III) Cl 2 Cl Cl Cl I (LXVIII) Scheme ii) Sulphonation of the benzimdazole can be carried out in Conc. Sulphuric acid or in chlorosulphonic acid to yield benzimidazole-5- sulfonic acid S 4 or ClS 3 3 S (III) (LXIX) Scheme iii) itration of the benzimdzole in presence of nitrating mixture gives a mixture of 5, 6 or 4, 6-dintrobenzimidazole S 4 / (III) 2 (LXX) (LXXI) Scheme

24 iv) Alkylation of benzimidazoles:- a) Alkylation: alkylation of alkyl halides usually occurs by SE 2 mechanism. b) Alkylation by Mannich reaction :- alkylation of benzimidazole by Mannich reaction 156 procedure. C 2 / morpholine C 2 C 3 (III) (LXXII) (III) PhC(C 2 ) 2 2 Xylene (C 2 ) 2 CPh (LXXIII) Scheme c) Alkylation by activated alkenes :- Benzimidazole derivatives have been alkylated by activated alkenes in thermal conditions and also in acid and base catalysed processes. C C C 2 (III) (LXXIV) C 2 -C 2 -C Scheme d) Activated alkynes:- 1-Vinylbenzimdiazole is formed by the reaction of benzimidazole with acetylene in aqueous dioxane at 160 o C

25 C C C C 2 aq.dioxane (III) (LXXV) Scheme eactions with ucleophilic reagents:- a) Tschitsichibabin reaction:- The tschitsichibabin reaction is extensively used for the preparation of 2-aminobenzimidazole derivatives. a 2 / xylene (LV) (LXXVII) 2 Scheme b) eaction with reactive intermediates:- Benzimidazole -2- carboxamide (LXXVII) is prepared by the reaction of benzimidazole (III) with a carboxylic acid in the presence of ammonium thiosulphate % 2 S 4 / Ag 3 / ( 4 ) 2 S 2 8 C 2 / 2 (III) (LXXVIII) C 2 Scheme c) eaction with benzyne:- Benzimidazole (III) reacts as a nucleophile with benzyne in conventional fashion to give 1- phenylbenzimidazole (LXXIX) along with polymeric materials

26 benzyne C Polymeric materials (III) (LXXIX) Scheme Photochemical reactions:- Benzimidazole (III) on irradiation with UV light transforms into a mixture of dehydroisomers, the two dimmers are formed by homolyic substitution at the 4 and 5 positions of benzimidazole by a 2-benzimidazolyl free radical. 163 (III) Et nm (LXXX) + (LXXXI) Scheme xidation:- xidation of benzimidazole (III) with lead dioxide gives 2,2 -biisobenzimidazolylidine (LXXXII). Alternatively, the compound can also be prepared by a similar oxidation of 2, 2 - biisobenzimidazole. 164 Pb 2 / C 6 6 / reflux Pb 2 / C 6 6 / reflux 24 hrs 24 hrs (III) (LXXXII) (LXXXIII) Scheme eduction:- Benzimidazoles on reduction with 2 in the presence of charcoal results in the formation of hexadehydrobenzimidazole (LXXXIV)

27 (III) 2 (100 atm) / h-c aq. Me (LXXXIV) Scheme Present Work:- It is evident from the literature that benzimidazoles are known to be biologically and pharmacologically important molecules. Also, not much work seems to have done on the synthesis of 1-substituted benzimidazole derivatives. Chapter 2: The present chapter deals with the studies on preparation of 2-Acetylbenzimidazole based on o-phenylenediamine. Condensation of o-phenylenediamine with lactic acid under Phillips conditions to give 2-(α-hydroxyethyl)benzimidazole, followed by oxidation studies with various oxidizing agents such as K 2Cr 2 7, Mn 2, 2 2 in Ac, CaCl 2, m-cpba,10% 3, 50% 3, CA has been described. This chapter also discuss the studies on reactions of 2-(αhydroxyethyl)benzimidazole with acid chlorides such as benzoyl chloride, benzenesulphonyl chloride and tosylation under various conditions and subsequently alkylations reactions on 2- acetylbenzimidazole and -benzoylated products. This chapter also describes the reactions of 2-(α-chloroethyl)benzimidazole with anilines. 38

28 Chapter 3: A study of literature showed that derivatives of thiadiazines, thiazolidinones and thiadiazol containing heterocyclic compounds have potential biological activity. Keeping this in view, it was considered worthwhile to study the synthesis of benzimidazole-2- acetyl thiosemicarbazone derivatives and their further chemical modifications. This chapter deals with the synthesis of 1, 3, 4-thiadiazolines. 2- Acetylbenzimidazole (4) on condensation with thiosemicarbazide gave thiosemicarbazone (82). The latter on condensation with p- chlorophenacyl bromide (83) gave 3-[1-benzimidazol-2-yl)- ethylideneamino]-4-(4-chlorophenyl)-3-thiazol-2-one (84). 84 on reaction with m-cpba in chloroform at (-)10 o C for 6 hrs yielded [1- (1-benzimidazol-2-yl)ethylidene]-[5-(4-chlorophenyl)-1,1-dioxo- 1,2,5,6-tetrahydro-1λ 6 -{1,3,4}thiadiazin-2-yl]amine (85). Chapter 4: The present chapter describes the alkylation studies on benzimidazole chalcones and subsequent functional modifications of resulting products into pyrazole and isoxazole derivatives. 2- Acetylbenzimidazole (4) was prepared by oxidation of 2-(αhydroxyethyl) benzimidazole (3) in acetic dichromate conditions. 4 on reaction with benzaldehyde in 5%a solution at room temperature for 3hrs resulted in the formation of known benzaldehyde chalcone (97). Benzimidazole-2-chalcone (97) on reaction with ethyl chloroacetate, in DMF containing K 2C 3 and catalytic amount of phase transfer catalyst TBAB, at room temperature for 1 hr resulted 39

29 in the formation of [2-(3-pheylacryloyl)benzimidazolyl] acetic acid ethyl ester (103). eaction of 103a with ab 4 in methanol at room temperature for 1 hr resulted in the formation of 1-[1-(2- hydroxyethyl)-1-benzimidazolyl]-3-phenyl propanol Acetylbenzimidazole (4) on heating with dimethyl formamide diemthyl acetal [C(Me) 2Me 2] at 105oC for 1 hr resulted in the formation of 1-(1-benzimidazolyl)-3-dimethylamino propenone (108). eaction of 108 with hydrazine hydrate in methanol on refluxing for 1 hr resulted in the formation of 2-(1-pyrazolyl)-1 benzimidazole 110. The isoxazole derivative of the benzimidazole was prepared by the reaction of 108 with 2.Cl in methanol under refluxing conditions for 3 hrs resulting in the formation of 2-isoxazolyl-1-benzimidazole (113). Chapter 5: It has been reported that pyrazolines possess analgesic, anti-inflammatory and antimicrobial activities. Therefore, it has been considered worthwhile to study the synthesis of pyrazoles hooked to benzimidazole ring system. This chapter deals with the synthesis of pyrazolyl derivatives of benzimidazole chalcone. 97 on reaction with dimethyl sulphate (DMS) in the presence of K2C3 and TBAB as PTC in C 3C at room temperature for 3 hrs yielded -methyl-2- acetylchalcone (129a, i.e., 129, =C 3) which is also known in literature. 129a (i.e., 129, =C 3) on refluxing with hydrazine hydrate in glacial acetic acid for 3 hrs resulted in the formation of 1-[3-(1- methyl-benzimidazole-2-yl)-5-phenyl-4, 5-dihydro pyrazol-1-yl] ethanone (130). 130 was condensed with different aromatic aldehydes such as benzaldehyde (14), in 10% methanolic a under reflux for 40

30 4 hrs resulting in 1-[3-(1-methyl-1-benzimidazol-2-yl)-5-phenyl-4, 5- dihydro-pyrazol-1-yl]-3-phenyl-propenone (132). 97 on reaction with malononitrile in the presence of sodium ethoxide in ethanol for 3 hrs at room temperature yielded a new product. This product was assigned as 6-(1-benzimidazol-2-yl)-2-ethoxy-4-phenyl nicotinonitrile (136). 97 on reaction with melononitrile in the presence of sodium methoxide in methanol for 3 hrs yielded a new product 6-(1-benzimidazol-2-yl)-3-methoxy-2-phneyl-isonicotinonitril (137). 137 on reaction with hydrazine hydrate in the presence of BF 3 in ethanol under reflux for 3 hrs yielded a product (138). 41

Fe (III), Co (II), Ni(II), Cu(II) -3,3'-(5- -1,2,4- Co(II), Ni(II) 121

Fe (III), Co (II), Ni(II), Cu(II) -3,3'-(5- -1,2,4- Co(II), Ni(II) 121 .. -1,2,4-2002 3 .,. -1,2,4- / -. :. 2002. 240.,, - -1,2,4-. (5-, - (), - -3,3-(5--1,2,4- - :, -..,, -,, -. :.. ; -. ; - - ().., 2002.,., 2002 4 3 8 10 1. -1,2,4-, 5--1()-1,2,3,4-14 1.1. -1,2,4-14 1.2.