Water and ionic liquid synergy

Journal of Saudi Chemical Society (2014) xxx, xxx–xxx

King Saud University

Journal of Saudi Chemical Society www.ksu.edu.sa www.sciencedirect.com

ORIGINAL ARTICLE

Water and ionic liquid synergy: A novel approach for the synthesis of benzothiazole-2(3H)-one Malik A. Waseem, Shireen, Arjita Srivastava, Anjali Srivastava, Rahila, I.R. Siddiqui * Laboratory of Green Synthesis, Department of Chemistry, University of Allahabad, Allahabad 211002, India Received 11 January 2014; revised 9 May 2014; accepted 15 May 2014

KEYWORDS Water; Ionic liquid; Benzothiazole-2(3H)-one; Ambient temperature; Novel methodology; Heterocyclization

Abstract Synergy between water, a green reaction medium and ionic liquid, a green catalyst has opened new vistas in the field of organic transformation. The developed methodology has emerged as an interesting combination for an environmentally benign, facile and efficient synthesis of benzothiazole-2(3H)-one. Product was achieved in excellent yield by the reaction of structurally diverse 2-iodoanilines with potassium thiocyanate. The strategy involves nucleophilic substitution forming NAC and SAC bonds resulting in the desired heterocyclic scaffold. This novel approach is also helpful for the synthesis of other related heterocycles for the development of an important drug like library. The reaction proceeded smoothly at an ambient temperature. ª 2014 Production and hosting by Elsevier B.V. on behalf of King Saud University.

1. Introduction Sustainable chemistry for synthesis has demonstrated its nature as an aesthetically appealing endeavour and as a scientifically important discipline. As a science of the future it has attracted some of the most creative minds to develop new methodologies throughout the world. The pressing need of today is to develop environmentally benign methodologies in the chemical industry, which shows exemplarily that the applications of green chemistry will solve huge challenges that come into play in future [1,2]. The encouraging use of eco-friendly * Corresponding author. Tel.: +91 9335153359; fax: +91 532 2461157. E-mail address: [email protected] (I.R. Siddiqui). Peer review under responsibility of King Saud University.

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chemicals, solvents and catalysts in recent times has already opened the door for future development and it ensures sustainable industrialization. Therefore, it is necessary to address and apply eco-pure chemistry. Volatile organic solvents (VOLs) are ecologically toxic, harmful and expensive. Since solvents are unavoidable as they play a key role, and are necessary for reaction mixing and product isolation, use of eco-safe solvents in organic transformation has recently attracted the attention of synthetic chemists worldwide. Reactions successful in water are the need of today and the demand of the future, because of their non hazardous nature and high solvating ability of water. Moreover high heat capacity, hydrogen bonding ability, large dielectric constant, optimum oxygen solubility, non-flammability, and inexpensive nature of water are properties very useful in synthetic chemistry [3]. Water is generally used as a cheap, safe, and environmentally benign solvent and offers easy workup for product isolation. In particular, water is best known to enhance and accelerate reaction rates [4,5].

1319-6103 ª 2014 Production and hosting by Elsevier B.V. on behalf of King Saud University. http://dx.doi.org/10.1016/j.jscs.2014.05.006 Please cite this article in press as: M.A. Waseem et al., Water and ionic liquid synergy: A novel approach for the synthesis of benzothiazole-2(3H)one, Journal of Saudi Chemical Society (2014), http://dx.doi.org/10.1016/j.jscs.2014.05.006

2

M.A. Waseem et al. CH 3

R

R R

N NH 2 S

S

N

H

R

I 1(a-k)

N

NH S

N H

Table 1 Influence of solvents and base on product yield and reaction time.

N

KOH [bmIm]Br

O

Water

S2

R

Few examples of biologically active molecules of benzothiazole-2(3H)-one.

Figure 1

NH2

O

N

N

S

R 3 (a-k)

Scheme 1 Synthesis of substituted benzothiazinone from iodoaniline and potassium thiocyanate under green conditions.

Nowadays ionic liquid has emerged as a new recyclable catalyst system, and in many of the heterocyclization reactions ionic liquid has played a key role in reaction initiation. Ionic liquid has been considered eco-safe with its tunable properties viz. insignificant vapour-pressure, non-flammability, high thermal, chemical and electrochemical stability and excellent catalytic activities. The recycling nature of ionic liquids makes them highly useful and versatile in organic synthetic chemistry [6–8]. The potential of ILs to provide a non-volatile solvent system has become a practical target for reducing waste. Benzothiazole is a noble moiety and has a number of biological properties associated with it. Prominent among them are anti Alzheimer’s and anti-cancerous activities. Moreover, it also possesses anti-ulcer, anti-bacterial, anti-viral, anti-diabetic and anti-inflammatory activities [9–11]. Few examples of important benzothiazole derivatives are given in Fig. 1.

S. No.

Solvent

Base

Time (h)

Yield (%)

1 2 3 4 5 6 7 8 9 10 11

[bmIm]Br Methanol Water THF Ethanol DCM DMF 1,4 dioxane Water + [bmIm]Br [bmImBr] Hexane

– – DBU Et3N K2Cr2O7 KOH NaOH Cs2CO3 – KOH Pyridine

24 12 12 12 12 12 12 24 36 24 36

– – – – – 11 – – – – –

Based on the elated significance of water, ionic liquid and benzothiazole-2(3H)-one and in continuation of our programme of developing new synthetic methodologies [12–18], herein we report an expeditious, facile, ionic liquid catalysed, water accelerated synthesis of substituted benzothiazole2(3H)-one derivatives from readily available 2-iodoaniline and potassium thiocyanate under basic conditions (Scheme 1).

NH R

HO

N

S

O

H N

N S

S O

R NH2

R

NH2

O

R

H2N

NH2

O S

R

H N

N

R O

NH2

H2N

H N NH

N O

OH

S

NH

R

NH2 OCH3

HN

SH

H N R

S S

S N

NH2

S

S

R

R NH S

OCH3

N S

O

R

S

H N

N

N H

R

Figure 2

Diversity of benzothiazole-2(3H)-one protocol.

Please cite this article in press as: M.A. Waseem et al., Water and ionic liquid synergy: A novel approach for the synthesis of benzothiazole-2(3H)one, Journal of Saudi Chemical Society (2014), http://dx.doi.org/10.1016/j.jscs.2014.05.006

Water and ionic liquid synergy Table 2

3

Influence of different ionic liquids on product yield and reaction time with and without bases in different solvents.

S. No.

Ionic liquid

Solvent

Base

Time (h)

Yield (%)

1 2 3 4 5 6 7 8 9 10 11

[bmIm]Br [bmIm]OH [bmIm]Cl [bmIm]BF4 [bmIm]Br [bmIm]Cl [bmIm]BF4 [bmIm]Br [bmIm]Br [emIm]Cl [bmIm]BF4

Methanol Water THF Ethanol DCM DMF 1,4-dioxane Water Water DMF DMSO

–

12 12 12 12 9 7 6 5 11 9 9

– 61 – – 83 73 81 90 69 65 64

– – K2CO3 NaOH KOH KOH Et3N Pyridine DMAP

In this work, we have planned and successfully achieved an ecologically pure and efficient method to prepare a number of fused benzothiazole-2(3H)-one derivatives via nucleophilic substitution followed by heterocyclization under simple and eco-compatible reaction conditions. Keeping in mind the facts of industrial need, where reaction conditions are the main issues, because human efforts are directly involved in the manufacture of life saving drugs, and after a careful study of previously reported work where hazardous catalysts like Rh, Cu, Pd, Br2 and unwanted solvents like DMF, DCM, DMSO, hexane, toluene, ethanol, glacial acetic acid and unavoidable carcinogenic bases, like Cs2CO3, DBU, and pyridine have already been used in standard reaction conditions which are unsatisfactory and harsh for the environment [19–26], there is a demand to develop a straightforward, efficient and high yield-

Table 3

ing protocol with high atom economy at ambient conditions from easily available starting materials. We have replaced toxic catalysts, hazardous bases and carcinogenic volatile organic solvents by recyclable and non toxic [bmIm]Br, non hazardous KOH and non carcinogenic water resulting in the betterment of the product yields (90%). Further the substituents present on reactants have considerable effect on the yield of the target molecules 3a–k. Table 4 clearly shows that substrates with electron donating groups react faster with excellent yield than compounds with electron withdrawing groups. Further the product containing the carbonyl group has the potential to react with the compounds having NH2, SH, and OH groups to form a number of useful protocols that lead to a biological library of compounds which provide wide scope to the methodology. (Fig. 2).

Effect of different mol% of [bmIm]Br and mol% of base in water on product yield and reaction time.

S. No.

Mol% of [bmIm]Br

Mol% of base

Solvent

Time (h)

Yield (%)

1 2 3 4 5 6

5 10 15 20 25 30

2 3 5 7 9 12

Water Water Water Water Water Water

7 7 5 7 7 7

69 77 90 82 74 65

N

N

I

I KOH

R

N

R NH

NH2 1

I S NH

R N H

S 2

S

S O

R N H

3 N

-NH3

R

H

O

H

S NH2

O NH H

R

NH N OH HH

N

Br

Scheme 2

Proposed mechanism of substituted benzothiazine in water catalysed by [bmIm]Br under basic conditions.


4

M.A. Waseem et al. Table 4 S. No.

Effect of electron donating and electron withdrawing groups on product yield and reaction time. 1 (a–k)

Product 3 (a–k)

1

NH2

H N

I

S

2

I

Br

3

NH2

H N

I

S

NH2

H N

I

S

O

85

4

85

4

86

3

90

4.5

80

4

81

3.5

83

3

87

4

85

4

83

O

O

5

NH2

H N

I

S

6

I

F

O

S

O2N

NH2

O

H N

NH2 O2 N

H N

F

O

I

O

S O

Cl

NH2

H N

Cl

O

I

S

O

O

9

O

10

3.5

O

4

8

90

O

O

7

3

O

S

Br

Yield (%)

O

H N

NH2

Time (h)

NH2

H N

I

S

O O

O

O H N

NH2

O S

I

11

O

OH

O

I

OH H N O

NH2

S


Water and ionic liquid synergy

5

2. Result and discussion At the outset of our preliminary investigations aiming to overcome reported harsh reaction conditions, the reaction was performed in an ionic liquid [bmIm]Br, no progress of reaction was observed even up to 12 h, we continued the stirring till 24 h but still the product was not observed. Then the combination of water and [bmIm]Br was used. However, no reaction progress was observed even after the reaction mixture was stirred up to 36 h at 75 C. Then we started to investigate the reaction in different solvents using reactants 1a and 2 with and without bases (Table 1). Surprisingly the reaction initiation was observed only in DCM with low yield (11%) and the rest of the solvents failed to produce conversion of reactants to products. As part of our eco-compatible research programme, ionic liquids were used as catalysts in different solvents (Table 2). Luckily this time product formation was observed in all organic solvents. The main breakthrough was observed when the reaction was performed in water in basic medium. In order to improve product yield, different bases were tried and finally inorganic bases produced better results with an outstanding product yield (90%) (Table 2, entry 8). The reaction proceeded smoothly and quantitatively at ambient condition with high yields, using water as a green reaction medium and basic [bmIm]OH as a recyclable catalyst system (Table 2, entry 2). This assured us that the reaction needs a base. Although, rest of the ionic liquids fail to convert the reactants into product in the absence of a base but [bmIm]OH which is capable of playing the role of a catalyst as well as a base, provides good yields even without the need of additional base. However, taking into consideration the better atom economy and yields obtained in the presence of [bmIm]Br and KOH, they have been selected in standard reaction conditions. Simplicity of the work up process for [bmIm]OH and the ease of its synthesis in the lab, make it a good reaction promoter, the experimental procedure involving [bmIm]OH has also been fully elaborated in the experimental section. After a careful investigation of the reaction in different ionic liquid catalytic systems with different bases and in different solvents Table 2, entry 8 emerged to be the best in terms of reaction time and with a splendid yield of 90%. Having the perfect reaction condition in hand and to make the reaction conditions more precise and more valuable from a practical point of view, we next investigated the effect of mol% of [bmIm]Br and mol% of base in water. Different mol% of [bmIm]Br and KOH were tested and it was inferred that 15 mol% (Table 3 entry 3) gave the highest yield. Surprisingly on increasing mol% of [bmIm]Br yield of the product decreased that seemed to be good from an economic point of view (Table 3). Based on the above mentioned results, clear and reasonable reaction path for benzothiazole-2(3H)-one from readily available 2-iodoaniline and potassium thiocyanate has been illustrated in Scheme 2. Product formation takes place only on application of the base changing the mechanistic path. As per normal way the reaction should proceed simply first by a sulphur anion attack on iodoaniline but as the reaction fails without a base the reaction path probably changes. Here first the base removes a proton from NH2 of 2- iodoaniline and an aniline nucleophile was generated that attacks the strong

Figure 3

Recyclability of ionic liquid [bmIm]Br.

electrophilic site created by the ionic liquid due to electrostatic attraction to the cyanate part of potassium thiocyanate to generate intermediate II that provides enough opportunity for S- to remove iodine from 2-iodoaniline leading to intramolecular heterocyclization yielding a highly stable and biologically active substituted benzothiazinone (Scheme 2). (See Table 4). We finally turned our examination towards the most important part of this tutorial i.e. recyclability and reuse of [bmIm]Br. The following considerations might be instructive in attempting to understand the way of thinking in which outstanding results of recyclability and reuse of ionic liquid with an interesting product yield were obtained. The first recycled [bmIm]Br gave only 2% product loss. Enthusiased by the activity of recyclable [bmIm]Br we again recycled and reused it and a 5% product decrease was observed. Accordingly for the 3rd, 4th and 5th reversible runs of [bmIm]Br product yield decreases by 7%, 8% and 10% (Fig. 3). The procedure for recycling and reuse of [bmIm]Br has been explained in the experimental section. 3. Conclusion In summary, superior domino reaction methodology has been developed for the synthesis of biologically significant benzothiazole-2(3H)-one under eco-compatible conditions with shorter reaction time from easily available starting materials. Owing to the reuse and ease of recovery of ionic liquid with a small decrease in product yield, out of the the protocol emerged a wonderful green catalyst. The heterocyclization reaction at room temperature and functional group interconversion provide wide scope to the methodology. The reaction condition would also be fruitful for other heterocyclic synthesis. The method is new and highly advanced over others, in terms of reaction time, product yield and workup process. Recyclability and reuse of [bmIm]Br after the reaction completion overall ended the strategy in a splendid manner. Acknowledgments Malik Abdul Waseem and Shireen Siddiqui gratefully acknowledge the UGC, New Delhi for a research Grant in the form of project and the Department of Chemistry, University of Allahabad, Allahabad for academic facilities. The authors would also like to thank SAIF, Chandigarh for spectral analysis.


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