As extension to our curiosity of getting new molecule with different heterocycles, we explored a useful molecule isatin. The synthetic versatility of isatin has led to the extensive use of this compound in organic synthesis. Three reviews have been published regarding the chemistry of this compound: the first by Sumter, in 1954 ^[1], a second by Popp in 1975 ^[2] and the third on the utility of isatin as a precursor for the synthesis of other heterocyclic compounds. ^[3]Synthetic versatility of isatin has stemmed from the interest in the biological and pharmacological properties of its derivatives. In this aspect, we condensed already synthesized hydrazides (1a and b) with isatin to yield the schiff bases.^{[4, 5]} Synthetic scheme is as follows.

Scheme-1

Synthesis of carbohydrazide (1a and b).

Benzo[d]isoxazol-3-yl-acetic acid hydrazide (1a):

Benzoisoxazole-3-acetic acid 1.65g, 10mmol (10) was dissolved in ethanol 10ml. Thionyl chloride 0.5ml was added to above solution and was heated to reflux. After 3 hrs solution was cooled and was poured to cold water 50ml. After 30 minutes reaction mass was extracted with 3 X 20ml chloroform. Organic layer was washed with water 20ml X 2 and dried over sodium sulphate. Organic layer was concentrated to oil. Ethanol 10ml was added to above solution. Hydrazine hydrate 0.4 ml, 10 mmol and catalytic amount 0.1 ml of acetic acid was added to above ester solution. Reaction mixture was heated to reflux for 1 hour. After cooling product was filtered and washed thoroughly with cold ethanol. Ethanol washing and filtrate was decomposed with water to get second crop of hydrazide. Product crystallized from ethanol.

M. p. 168⁰C, Yield - 79%

IR(KBr) 1643 cm^-1 (carbonyl), 2866 cm^-1 , 3054 cm^-1, 3312 cm^-1(CH₂, NH, NH₂).

Synthesis of (2-Benzo[d]isoxazol-3-ylmethyl-benzoimidazol-1-yl)-acetic acid hydrazide (1b):

Hydrazine hydrate (0.4 ml, 10 mmol) and catalytic amount 0.1 ml of acetic acid was added to (2-Benzo[d]isoxazol-3-ylmethyl-benzoimidazol-1-yl)-acetic acid ethyl ester (2.05 g, 10mmol) solution. Reaction mixture was heated to reflux for 1 hr. After cooling product was filtered and washed thoroughly with cold ethanol. Product was crystallized from ethanol.

M.p- 220-221⁰C; Yield 77 %.

IR (KBr) -3300 and 3322cm^-1(-NH-, -NH₂- band), 3052cm^-1

(-CH₂-) 1662cm^-1,(-CO- hydrazide carbonyl).

H¹NMR-δ 9.6 (s, 1H, amidic NH), δ 7.1-7.7(m, 8H, 8 Ar ), δ4.9 (s, 2H, -CH₂- carbonyl adjacent), δ 4.7 (s, 2H, -CH₂- iso-oxazole ring adjacent), δ 4.3 (NH₂)

Preparation of (2-Benzo[d]isoxazol-3-ylmethyl-benzoimidazol-1-yl)-acetic acid ethyl ester:

3-(1H-benzoimidazol-2-ylmethyl)-benzo[d]isoxazole (1.77g, 10 mmol) was dissolved in 10ml of DMF, to the above mixture finely powdered anhydrous K₂CO₃(15 mmol) was added. (1.36g, 12 mmol) of chloroethylacetate was added drop wise to above solution at room temperature. Reaction mixture was heated to reflux. Reaction was monitored on Thin Layer chromatography for completion of reaction and it was completed in 4hrs. After cooling reaction mixture was decomposed in water. Reaction mixture was neutralized with dil. HCl. Solid product was filtered and washed thoroughly with water. Product was crystallized with alcohol

M.p-.100-103⁰C, Yield- 67%.

IR(KBr)- 1742cm^-1ester carbonyl, (3400 cm^-1-NH-broad band absent)

Product was identified as (2-Benzo[d]isoxazol-3-ylmethyl-benzoimidazol-1-yl) acetic acid ethyl ester

3-(1H-benzimidazol-2-ylmethyl)-benzo[d]isoxazole:

3-(1H-benzimidazol-2-ylmethyl)-benzo[d]isoxazole was prepared from benzo[d]isoxazole 3- acetic acid(10) using Phillip’s method for synthesis of benzimidazoles as per literature.^6,7.

M.p: - 174⁰C; Yield 81 %.

IR(KBr)- 3400 cm^-1(Broad imidazole –NH-)

H¹ NMR-d 12.5 (s, 1H, -NH), d7.0 -7.8 (m, 8H, Ar proton), d 4.6 (s, 1H,-CH₂).

Condensation of carbohydrazide (1a and b) with isatin

2-(1,2-benzisoxazol-3-yl)-N'-[2-oxo-1,2-dihydro-3H-indol-3-ylidene]acetohydrazide (3a):

Compound Benzo[d]isoxazol-3-yl-acetic acid hydrazide (1a) (0.201g, 1.0 m.mol) and isatin (2) (0.179g, 1.0m.mol) was dissolved in ethanol and heated to reflux. Catalytic amount of acetic acid was added. Reaction was monitored on Thin Layer chromatography was complete in 4 hrs. After completion of reaction, product filtered and was thoroughly with cold ethanol. Product was purified by crystallization in ethanol, yield (0.203g) 56%, M.p.-234⁰C.

H¹NMR-δ 12.8 (s, 1H, amidic NH), δ 10.9(s, 1H, NH, isatin ring NH), δ6.9-8(m, 8H, Ar), δ 2.7 (s, 2H, -CH₂-).

Mass- m/z 321 [M+H]⁺,

Composition (cal) = C (63.75%) H (3.78%) N (17.49%)

Composition (obs) = C (65.916%) H (3.686%) N (17.701%)

Following similar procedure (2-Benzo[d]isoxazol-3-ylmethyl-benzo imidazol-1-yl)-acetic acid hydrazide (1b) was condedensed with isatin (2) to give (2-

Benzo[d]isoxazol-3-ylmethyl-benzo imidazol-1-yl)-N'-[(3Z)-2-oxo-1, 2-dihydro-3H-indol-3-ylidene] aceto hydrazide (3b)

Product crystallized with ethanol. Yield 61 %, M.p 260⁰C.

IR(KBr)- 3453cm^-1(-NH-), 1704cm^-1(Doublet carbonyl)

H¹NMR-δ 11.9 (s, 1H, amidic NH), δ 10.8 (s, 1H, isatin ring NH), δ 6.9-8.1 (m, 12H, Ar), δ 5.8 (s, 2H, -CH₂- adjacent to iso-oxazole ring), δ 3.3 (s, 2H, -CH₂- adjacent to carbonyl).

Mass- m/z 451.29 [M+H] ⁺

ACKNOWLEDGEMENT:

Authors thank Director, SAIF IIT, Mumbai, for providing important analysis. We are also thankful to micro-analytical laboratory, Dept. of Chemistry, University of Mumbai, for providing spectral analysis.

REFERENCES:

1. Sumter, W.C. Chem. Rev. 1954, 34, 407

2. Popp, F.D. Adv. Heterocycl. Chem. 1975, 18, 1.

3. Shvekhgeimer, M.G.A. Chem. Heterocycl. Compd. (Engl. Transl.). 1996, 32, 249.

4. V.V.Mulwad, A C. Chaskar, Indian J Chem, 2006, 44B, 1465.

5. U.C. Mashelkar, A.A. Audi, Ind J. Chem., 45B, 1963.

6. Phillips M. A., J. Chem. Soc. 2393 (1928).

7. Vaidya S. D.; Siva Kumar B.V.; Mashelkar U.C.; Indian J. Heterocyclic. Chem 14,197,(2005).

Received on 10.07.2014 Modified on 15.07.2014

Asian J. Research Chem. 7(9): September 2014; Page 781-782