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An Aerobic Oxidative Coupling Approach for The Synthesis of N-Substituted 2-Aminobenzothiazole Derivatives using Iron Catalyst.

Volume 32, Number 3

N. V. Anil Kumar, Shailesha Kamath, Santosh L. Gaonkar and Nitinkumar S. Shetty*

Department of Chemistry, Manipal Institute of Technology, Manipal University, Manipal – 576104, India.

Corresponding Author E-mail: snitinshetty@gmail.com; 

DOI : http://dx.doi.org/10.13005/ojc/320349

Article Publishing History
Article Received on : March 26, 2016
Article Accepted on : April 30, 2016
Article Published : 11 Jun 2016
Article Metrics
ABSTRACT:

A facile and convenient method was developed for the formation of novel N substituted 2-aminobenzothiazoles via an iron-catalysed condensation of 2-aminobenzothizole with different amines. This method is applicable for a wide range of aliphatic, aromatic and heterocyclic amines furnishing moderate yields of the corresponding products and thus rendering the methodology as a highly eco-friendly, inexpensive alternative to the existing methods.

KEYWORDS:

2-Aminobenzothiazole; N-substituted; synthesis; aerobic oxidative coupling; Iron catalyst

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Kumar N. V. A, Kamath S, Gaonkar S. L, Shetty N. S. An Aerobic Oxidative Coupling Approach for The Synthesis of N-Substituted 2-Aminobenzothiazole Derivatives using Iron Catalyst. Orient J Chem 2016;32(3).

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Kumar N. V. A, Kamath S, Gaonkar S. L, Shetty N. S. An Aerobic Oxidative Coupling Approach for The Synthesis of N-Substituted 2-Aminobenzothiazole Derivatives using Iron Catalyst. Orient J Chem 2016;32(3). Available from: http://www.orientjchem.org/?p=17425

Introduction

Substituted benzothiazoles exhibits various biological and therapeutical activities.[1, 2]Aminobenzothiazoles are synthesised by employing various catalysts: cobalt was used by Zhu [3, 4], palladium by Vera 5, copper by Saha 6 and Khatun 7, nano copper oxide 8, 9. Other methods of synthesising aminobenzothiazoles is by Herz method10, solid phase synthesis 11, using benzyltrimethylammonium tribromide 12 or sodium dichloroiodate 13, starting from o-nitroaniline 14 or in water 15. Apart from synthesis, following biological activities were reported: Aurora-A kinase inhibitor 16, calcium channel blockers 17, anti-cancer 18, 19, herbicidal activity20, mitochondrial apoptotic inducers 21, neuronal nitric oxide synthase inhibitor22, anti-inflammatory 23, 24, antimalarials 25, antimicrobial 26, 27

Oxidative coupling reactions with amines are reported in literature. Zhou et al 28, 29 used boron-dipyrromethene (BODIPY) under mild condition, Yu et al30 used oxone and trifluoroacetic acid in PEG-400 for the green method. Also, various metals are used for these conversions: gold [31], gold nanoparticle [32], copper [33], silica supported vanadium [34], ruthenium [35] and cobalt[36].

Synthesis of N-substituted amines reported in literature does not use iron as catalyst. In view of these reports and literature, attempt was made to synthesize novel N-substituted aminobenzothiazole derivatives using iron as catalyst via oxidative coupling route.

Results and Discussion

Different iron compounds (FeCl3, FeCl2, FeCl2.2H2O, FeSO4.7H2O, Fe(OAc)2 and  FeBr2) were used for the optimisation. The reactions (scheme-1) were carried out with 10% mol of the catalyst and found that FeBr2 results in 63% yield. Therefore, concentration of the catalyst was further reduced to 5% and 2%. This resulted in 64 and 29% yields respectively. Also the effect of the inert medium was evaluated by using N2 and Ar environment and that resulted in 6 and 3% yields respectively. Hence the concentration of FeBr2 was optimised at 5% mol.

Scheme 1: Reaction scheme for the optimisation of the reaction conditions. Scheme 1: Reaction scheme for the optimisation of the reaction conditions.

Click here to View Scheme

 

While optimising the concentration of the catalyst, the reactants were used 1.5 equivalents of aminobenzothiazole and 1 equivalent of benzylamine. After finalising the concentration of the catalyst, the reactants concentrations were changed to 1 and 2 equivalents respectively and the yield obtained was only 48%. It has been found that FeBr2 gave better yields amongst all other iron catalysts used. To optimise the conditions, different concentrations were used and 5% mol found to be the optimum concentration without the usage of inert conditions (Table-1). To substantiate our proposed mechanism (scheme – 3), we have carried out the reactions in inert conditions. During the process, oxygen starved environment has yielded very low product.

 

Table 1: Optimisation Parameters For The Synthesis Of N-Substituted Aminobenzothiazoles.

Entry

Catalyst

(% mol)

Environment,

(%mol of 2 amino benzothiazole :  %mol of Benzylamine)

Isolated yield (%)

1

FeCl3 (2% mol)

Air, (1.5:1)

Traces

2

FeCl2 (10% mol)

Air, (1.5:1)

Traces

3

FeCl2.2H2O (10% mol)

Air, (1.5:1)

Not recovered

4

FeSO4.7H2O (10% mol)

Air, (1.5:1)

Not recovered

5

Fe(OAc)2 (10% mol)

Air, (1.5:1)

Not recovered

6

FeBr2 (10% mol)

Air, (1.5:1)

63

7

FeBr2 (5% mol)

Air, (1.5:1)

64

8

FeBr2 (2% mol)

Air, (1.5:1)

29

9

FeBr2 (10% mol)

N2, (1.5:1)

6

10

FeBr2 (10% mol)

Ar, (1.5:1)

3

11

FeBr2 (10% mol)

Air, (2:1)

48

12

No catalyst

Air, (1.5:1)

Not recovered

 

Under these optimised conditions, various N-substituted 2-aminobenzothiazoles (3 a – e) were synthesised from their corresponding amine (2 a – e) and 2-amino benzothiazole (1) (scheme – 2). These newly synthesised compounds were characterised by IR, NMR and MS. In order to cross check applicability for different amines, aromatic, aliphatic and heterocyclic substrates were employed and produced moderate yields. Here we are reporting the iron as catalyst via oxidative coupling approach for the synthesis of novel N-substituted aminobenzothiazole derivatives (3 a – e).

Scheme – 2: General Reaction Scheme For The Various N-Substituted Aminobenzothiazoles. Scheme 2: General Reaction Scheme For The Various N-Substituted Aminobenzothiazoles.

Click here to View scheme

 

Scheme-3: Possible mechanism

Scheme 3: Possible mechanism

 

 


Click here to View Scheme

 

Experimental Section

General procedure

Iron catalyst was added to a two-necked, round-bottom flask containing the 2-aminobenzothiazole and an amine at room temperature. The resulting reaction mixture was heated at 110o C for 24 h. The progress of the reaction was monitored by TLC. After 24 hours, the reaction mixture was directly purified using column chromatography.

N-benzylbenzo[d]thiazol-2-amine (3a): The title compound was synthesised as per the general method using benzyl amine. Yield: 64%. Mp: 244-246ºC.1H NMR (400 MHz, DMSO-d6):  8.52 (s, 1H, NH), 7.68 – 7.00 (m, 9H, aromatic), 4.60 (s, 2H, CH2). 13C NMR (75 MHz, DMSO -d6):  166.6, 158.8, 152.9, 131.2, 130.8, 129.3, 125.9, 121.4, 118.5, 48.7. Mol Wt: 240.32, m/z: 240.09. Anal. Calcd for C14H12N2S: C, 69.97; H, 5.03; N, 11.66; S, 13.34. Found: C, 70.05; H, 5.29; N, 11.80; S, 12.85.

N-(4-methoxybenzyl)benzo[d]thiazol-2-amine (3b): The title compound was synthesised as per the general method using 4-methoxybenzyl amine.Yield: 67%. Mp: 296-298ºC. 1H NMR (400 MHz, DMSO -d6):  8.43 (s, 1H, NH), 7.67- 6.89 (m, 8H, aromatic), 4.51 (s, 2H, CH2), 3.73 (s, 3H, OCH3).13C NMR (75 MHz, DMSO -d6):  166.6, 158.8, 152.9, 131.2, 130.8, 129.3, 125.9, 121.4, 118.5, 114.2, 55.5, 47.2. Mol Wt: 270.35, m/z: 270.21. Anal. Calcd for C15H14N2OS: C, 66.64; H, 5.22; N, 10.36; S, 11.86. Found: C, 66.91; H, 5.34; N, 10.41; S, 11.46.

N-butylbenzo[d]thiazol-2-amine (3c): The title compound was synthesised as per the general method using n-butyl amine.Yield: 72%. Mp: 199-201ºC. 1H NMR (400 MHz, DMSO – d6):  8.06 (s, 1H, NH), 7.96 – 7.08 (m, 4H, aromatic), 3.56 – 3.48 (t, 2H, NHCH2), 1.52 to 1.33 (m, 4H, CH2-CH2), 0.91 (t, 3H, CH3). 13C NMR (75 MHz, DMSO -d6): 166.6, 153.4, 130.8, 125.8, 121.4, 121.2, 118.4, 47.7, 40.5, 39.7, 39.4. Mol Wt: 206.31, m/z = 206.10. Anal. Calcd for C11H14N2S: C, 64.04; H, 6.84; N, 13.58; S, 15.54. Found C, 64.24; H, 6.99 N, 13.67; S, 15.08.

N-octylbenzo[d]thiazol-2-amine (3d): The title compound was synthesised as per the general method using n-octyl amine.Yield: 75%. Mp: 233-235ºC. 1H NMR (400 MHz, DMSO – d6):  7.99 (s, 1H, NH), 7.65 -6.97 (m, 4H, benzothiozol), 3.36 – 3.31 (t, 2H, NHCH2), 1.61 – 1.26 (m, 12H, CH2), 0.87 – 0.84 (t, 3H, CH3). 13C NMR (75 MHz, DMSO – d6): 166.6, 153.2, 130.7, 125.9, 121.2, 121.2, 118.3, 47.7, 40.8, 40.5, 40.0, 39.7, 39.4, 39.2. Mol Wt: 262.41, m/z = 262.01. Anal. Calcd for C15H22N2S: C, 68.66; H, 8.45; N, 10.68; S, 12.22. Found: C, 68.87; H, 8.57; N, 10.93; S, 11.63.

N-(thiophen-2-ylmethyl)benzo[d]thiazol-2-amine (3e): The title compound was synthesised as per the general method using 2-(Aminomethyl)thiophene.Yield: 59%. Mp: 199-201ºC. 1H NMR (400 MHz, DMSO – d6):  8.22 (s, 1H, NH), 7.51 – 6.98 (m, 7H, aromatic), 4.48 (s, 2H, CH2). 13C NMR (75 MHz, DMSO – d6):  166.6, 158.6, 152.8, 141.2, 131.4, 130.8, 129.3, 126.6, 125.9, 121.4, 118.5, 51.7. Mol Wt: 246.35, m/z = 246.09. Anal. Calcd for C12H10N2S2: C, 58.51; H, 4.09; N, 11.37; S, 26.03. Found: C, 58.67; H, 4.21; N, 11.42; S, 25.69.

Acknowledgement

All authors are grateful for the facilities provided by the Manipal Institute of Technology, Manipal affiliated with Manipal University to carry out this work.

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