Synthesis of some Sulphur and Nitrogen containing Heterocyclic Compounds

 

Varsha A. Dighe1*, Rohini R. Pujari2

1Department of Pharmaceutical Chemistry, Kasturi Shikshan Sanstha's College of Pharmacy, Shikrapur, Pune 412208, Maharashtra, India.

2Department of Pharmacology, PES Modern College of Pharmacy (For Ladies), Moshi, Pune, Maharashtra, 412105, India.

*Corresponding Author E-mail: varshadighe15@gmail.com

 

ABSTRACT:

A novel series of some substituted thiadiazole derivatives were synthesized by known standard methods using analytical grade chemicals with the aim to get better antidiabetic and antitubercular activity.  The structures of synthesized compounds were supported by means of physicochemical test and IR spectroscopy.

 

KEY WORDS: Thiadiazole, Antidiabetic, Antitubercular, Sulphur, Nitrogen.

 

 

 


INTRODUCTION:

In  recent  years  1,3,4-thiadiazole  derivatives  have  received significant  attention  and  have  been  increasingly  investigated  for  their diverse  range  of  biological  properties such as diuretic, antiprotozoal, cardiotonic, fungicidal, sedative, anesthetic, antimalarial, CNS depressant, hypoglycemic, antiinflammatory and antimicrobial activities1-5.

 

In light of this the present work was aimed at synthesizing new substituted 1,3,4 thiadiazole derivatives heterocycles to produce safer drugs with less toxicity towards anti tubercular and antidiabetic activities.

 

MATERIAL AND METHODS:

Scheme I: The synthesis of 1,3,4 thiadiazole derivatives comprises of 3 steps as follows:
1. Synthesis of 2-amino-5-aryl-1, 3, 4-thiadiazole (I):

A mixture of 0.1 mol of thiosemicarbazide, 0.1 mol of aryl carboxylic acid (salicylic acid, nicotinic acid, cinnamic acid) and 10 drops of conc. sulphuric acid was refluxed for 1 hr and poured into crushed ice. The resulting product was filtered and solid portion was separated. Solid product was washed and recrystallized from ethanol to give I.

 

2. Synthesis of substituted N-(5-aryl-1,3,4-thiadiazole-2-yl)-2-chloroacetamide (II):

0.5mol of substituted amino compounds were dissolved in 25ml of glacial acetic acid containing 25 ml of saturated solution of sodium acetate. The mixture was warmed and cooled in ice bath with stirring to completely dissolve the substituted amino compounds. To this 0.06 mol of chloroacetyl chloride was added drop wise so that vigorous reaction does not take place. After half an hour white a coloured product was separated and filtered. The product was washed with 50% aqueous acetic acid and finally with water. It was purified by recrystallization from absolute alcohol.

 

3. Synthesis of N-(5-(4-aminophenyl)-1, 3, 4-thiadiazole-2-yl)-2-(Sulphonophenylamino) acetamide (A1): A mixture of N-(5-(4-aminophenyl)-1,3,4-thiadiazole-2-yl)-2-chloroacetamide (0.01 mol) was taken in 25ml of absolute alcohol and 0.01 mol of aryl derivatives (sulphanilamide, pyrazinamide, INH) was added to it and refluxed for 4 hrs. The product obtained was separated, filtered and purified by recrystallization from aqueous alcohol. The compounds A1, A2, A3 were synthesized following a similar procedure6-8.

 

Infrared studies of synthesized 1,3,4 thiadiazole derivatives: 

Infrared  absorption  spectra  of  each  of  the  synthesized  compounds  were  obtained  by  preparing  KBr  pellet,  and  then  running  it  on  FTIR  spectrophotometer,  to  check the characteristic absorptions.

 

RESULTS AND DISCUSSION:

As per the previous literature aromatic and heterocyclic amines were used as starting materials for the synthesis of 2,5- disubstituted 1,3,4-thiadiazoles  Thiosemicarbazides were considered ideal for the  synthesis  of  some  heterocyclic  rings  and the cyclization of substituted thiosemicarbazides in acidic media  was used for the formation of 1,3,4-thiadiazoles9,10. The synthesis of 2-R-5-formyl-1,3,4-thiadiazole  derivatives  was  achieved through the synthetic routes outlined in Figure 1.

 

Fig. 1: Synthesis of 1,3,4 thiadiazole derivatives  by Scheme I

 

Infrared studies of synthesized 1,3,4 thiadiazole derivatives: The structures  of  the  synthesized  compound were determined on the basis of their FTIR study data. The spectral data for FTIR is elaborated in Figure 2,3,4 and Table 2,3,4, which confirms the structure of synthesized compounds (A1, A2, A3) given in Table 1.


 

 

 

Table 1:  Structures and IUPAC names of synthesized 1,3,4 thiadiazole derivatives  compounds

Compound

IUPAC

Structure

A1

N-[5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl]-2-[(4-sulfamoylphenyl)amino]acetamide

 

A2

N-(2-oxo-2-{[5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl]amino}ethyl)pyrazine-2-carboxamide

 

A3

2-[2-(pyridin-4-yl carbonyl)hydrazinyl]-N-[5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl]acetamide

 

 


 


 

Fig. 2: Infrared spectra of the synthesised 1,3,4 thiadiazole derivative A1 N-[5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl]-2-[(4-sulfamoylphenyl)amino]acetamide

 

 


Table 2: Interpretation of the Infrared spectra of the synthesised 1,3,4 thiadiazole derivative A1 (N-[5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl]-2-[(4-sulfamoylphenyl)amino]acetamide)

 

Functional group

Ranges

N-H

3480.88

C-H AROMATIC

3090.17, 2966.95

C-H ALKANE

2887.88

C=O

1740.44

O=C-NH- AMIDE

1806.97

 

 

Table 3: Interpretation of the Infrared spectra of the synthesised 1,3,4 thiadiazole derivative A2 (N-(2-oxo-2-{[5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl]amino}ethyl)pyrazine-2-carboxamide)

Functional group

Ranges

N-H

3480.88

C-H AROMATIC

3090.17, 2966.95

C-H ALKANE

2887.88

C=O

1740.44

O=C-NH- AMIDE

1806.97

AROMATIC RING

1503.24, 1595.81

SULPHONAMIDE

1173.47, 1138.76

C-S-C

646.03, 2083.71


 

Fig. 3: Infrared spectra of the synthesised 1,3,4 thiadiazole derivative A2 (N-(2-oxo-2-{[5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl]amino}ethyl)pyrazine-2-carboxamide)

 

Fig. 4: Infrared spectra of the synthesised 1,3,4 thiadiazole derivative A3 (2-[2-(pyridin-4-yl carbonyl)hydrazinyl]-N-[5-(pyridin-4-yl)-1,3,4-thiadiazol-2-yl]acetamide)

 

 


CONCLUSION:

The present work was aimed at synthesizing new heterocycles targeting for anti-tubercular and antidiabetic and to produce safer drugs with less toxicity. The new 1,3,4 thiadiazole derivatives were synthesised known standard methods and their structures were confirmed using infrared studies. Further studies are needed to carryout the biological screening of the synthesized derivatives for antitubercular and antidiabetic activities.

 

ACKNOWLEDGEMENT:

The authors are thankful to Principal, Department of Pharmaceutical Chemistry, Kasturi Shikshan Sanstha's College of Pharmacy, Shikrapur, Pune for  providing  all  the facilities  to  carry  out  the  extensive  research work.

 

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

 

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Received on 11.12.2016       Accepted on 12.01.2017     

© Asian Pharma Press All Right Reserved

Asian J. Pharm. Res. 2017; 7(1): 21-24.

DOI: 10.5958/2231-5691.2017.00004.1