Electro-generated ortho-quinoide intermediates:templates for feasible construction of a series of novelimidazo[2,1-b]thiazole derivatives through one-pot five-step domino hetero-annulation process

Abdolhamid Alizadeh • Mohammad M. Khodaei •

Tayyebeh Kanjouri • Mustaffa Shamsuddin

Received: 26 February 2014 / Accepted: 26 May 2014

� Springer Science+Business Media Dordrecht 2014

Abstract A series of novel polycyclic structures, with an imidazothiazole central core,

were successfully synthesized through the anodic oxidation of catechols in the presence of

2-imidazolidine thione, as nucleophiles in aqueous solution. The cyclic voltammetric results

indicated that one-pot multi-step sequential reactions occur between the electrochemically

derived o-benzoquinones intermediates and nucleophiles affording fused polyheterocyclic

compounds. The mechanism of these catalyst-free, tandem reactions are proved as ECECE or

ECECCE pathways using potentiostatic and galvanostatic coulometries. In addition, the

electrosyntheses of fused imidazo[2,1-b]thiazoles have been successfully performed in

ambient conditions in an undivided cell using an environmentally friendly method with high

atom economy and current efficiency. The novel fused polyheterocycles were fully char-

acterized by FT-IR, 1H NMR, 13C NMR, and HR-MS spectrometric methods.

Keywords Quinoide intermediates � Domino reactions � Imidazothiazoles �Potentiostatic � Galvanostatic � Heterocycles

Electronic supplementary material The online version of this article (doi:10.1007/s11164-014-1731-5)

contains supplementary material, which is available to authorized users.

A. Alizadeh (&) � M. M. Khodaei (&) � T. Kanjouri

Department of Organic Chemistry, Faculty of Chemistry and Nanoscience and Nanotechnology

Research Center (NNRC), Razi University, 67149 Bakhtaran, Iran

e-mail: ahalizadeh2@hotmail.com; ahalizadeh2@razi.ac.ir

M. M. Khodaei

e-mail: mmkhoda@razi.ac.ir

A. Alizadeh � M. Shamsuddin

Ibnu Sina Institute for Fundamental Science Studies, Universiti Teknologi Malaysia,

81310 UTM Skudai, Johor, Malaysia

123

Res Chem Intermed

DOI 10.1007/s11164-014-1731-5

Introduction

In recent years, the chemistry and synthesis of polycyclic compounds possessing an

imidazothiazole central core (Fig. 1i) has been the focus of great interest [1–3]. This is,

in part, due to the broad spectrum of biological properties of these compounds. Several

imidazo[2,1-b]thiazole derivatives have been reported in the literature as antibacterial

[4], antifungal [5], and antitumour agents [6]. For instance, the imidazo[2,1-b]thiazole

system constitutes the main part of the well-known antihelminthic and immunomod-

ulatory agent levamisole (Fig. 1ii), and a series of imidazo[2,1-b]thiazole guanyl

hydrazones (Fig. 1iii) have been proved to be active against various cancer cell lines [6].

Generally, the synthetic routes to these fused structures are as follows: (1) alkylations

of cyclic thioureas by appropriate 1, 2-dielectrophiles [7], or (2) condensations of

2-aminothiazoles with 1,2-difunctionalized units, such as a,b-unsaturated carbonyl

compounds [8]. Although several synthetic strategies are available, these suffer from

drawbacks including long reaction periods, toxic solvents, and/or metal additives, and,

therefore, facile and green routes to these structures would be of great interest. Electric

current is one of the cleanest tools in the transformation of organic molecules, and,

accordingly, several electrochemical techniques have provided a variety of highly

reactive intermediates affording useful and/or novel organic compounds without the use

of any environmentally undesirable catalysts [9–11]. In particular, direct electrochem-

ical oxidation/reduction of substrates practically utilizes electrons as the only reagents.

In this sense, electrochemistry is frequently referred to as one of the prototypical green

procedures for synthesizing various organic molecules and structures [12]. Catechols

are important species in chemistry and biology, because of their facility in undergoing

electron transfer [13] and being involved in the primary photoelectron donor–acceptor

center in bacterial photosynthesis [14]. The most important property of catechols is the

ease in which they undergo redox transformations, a very important physiological

reaction. Catechol species are electrochemically oxidized to very reactive intermediates

quinones which can undergo a nucleophilic attack by the nucleophilic species through a

1,4-Micheal addition pathway [15, 16].

In continuation of our efforts to develop versatile and convenient electrochemical

and chemical synthesis of highly functionalized heterocycles [17–20], we report

here the synthesis of a series of polycyclic compounds with imidazo[2,1-b]thiazole

central core (Fig. 1v) through a one-pot five-step electrooxidative-coupling

sequential fashion under two controlled-potential (CPC) and controlled-current

(CCC) coulometries. The protocol provides an efficient and clean entry to nitrogen-

and sulfur-containing heterocycles of type imidazo[2,1-b]thiazoles, the relatively

rare fused-ring systems, in excellent yields and electrochemical efficiencies.

Experimental

General

Cyclic voltammetric experiments were performed with a Voltametric Analyzer Model

Autolab PGSTST 101 and controlled potential and current coulometry, and

A. Alizadeh et al.

123

preparative electrolysis were performed using a coulometry BHP 2050 potentiostat/

galvanostat. The working electrode used in voltammetry experiments was a glassy

carbon disc (1.8 mm diameter) and platinum wire was used as the counter electrode.

The working electrode used in controlled-potential coulometry technique was an

assembly of a four-rod carbon cathode (5 cm2) and one rod of carbon constituted the

counter electrode. The working electrode potentials were measured versus SCE. In

controlled-current coulometry technique the anode electrode was one rod of carbon

(5 cm2) and the cathode electrode is a one-rod carbon electrode (5 cm2). 1H and 13C

NMR spectra were recorded on the spectrometers operating at 200 or 600 MHz for

proton and 50 or 150 MHz carbon nuclei. Mass spectra and exact masses were

recorded on a MAT 8200 Finnigan high resolution mass spectrometer; the latter

employed a mass of 12.0000 for carbon and the data are listed as follows: mass-to

charge ratio (m/z). Melting point of the product was monitored on a Barnstead

Electrothermal. A digital pH/mV/Ion meter (JENWAY pH Meter Model 3330) was

used for preparing of the buffer solutions, which were used as the supporting

electrolyte in voltammetric and coulometric experiments. All chemicals were reagent-

grade materials from E. Merck; and sodium acetate and other solvents and reagents

were of pro-analysis grade. These chemicals were used without further purification.

Typical procedure for the synthesis of polycyclic imidazothiazols through CPC

condition

Under CPC condition, in a typical procedure, an aqueous solution (ca. 100 mL) of

water/acetonitrile (90/10), containing 0.2 M sodium acetate, 1.0 mmol of catechols

(1a–f) and 1.0 mmol of 3, was electrolyzed in an undivided cell equipped with a

carbon cathode (an assembly of four rods, 6 mm diameter, and *10 cm length) and

a carbon anode at 0.30 V versus SCE, at 25 �C. The electrolysis was terminated

when the current decreased by more than 95 %. At the end of electrolysis, the cell

was placed in a refrigerator overnight and then the precipitated solids were collected

N

N

S

R2

R1

NN

S

O

O

iiiiii

v

N

N

S

N

N

S N

N

S

Cl

SHN

HN

O OR

R

iv

Fig. 1 Some typical polyheterocycles with an imidazothiazole moiety

Electro-generated ortho-quinoide intermediates

123

by filtration, washed copiously with distilled water, and the final products were

obtained purely, and no extra purification was needed.

Typical procedure for the synthesis of polycyclic imidazothiazols through CCC

condition

In the CCC procedure, aqueous solution (ca. 50 mL) of water/acetonitrile (80/20),

containing 0.2 M sodium acetate, 1.0 mmol of catechols (1a–f) and 1.0 mmol of 3,

at 25 mA, (current density = 5 mA/cm2) was electrolyzed. The process was

interrupted during the electrolysis and the graphite anode was washed in acetone in

order to reactivate it. At the end of electrolysis, the final products were collected by

filtration, washed copiously with distilled water and the final products were obtained

purely in high yield. These products were characterized by: FT-IR, 1H NMR, 13C

NMR and HR-MS.

2,3-Dihydro-benzo[d]imidazo[2,1-b]thiazole-6,7-dione (7a)

Dark red solid; decomposed at 186–188 �C.1H-NMR, (600 MHz, DMSO-d6) d 3.88 (t, j = 7.6 Hz, 2H), 4.67 (t, j = 7.6 Hz,

2H), 5.69 (s, 1H), 6.62 (s, 1H); 13C-NMR (DMSO-d6, 150 MHz) d 43.73, 62.6, 97.2,

123.6, 124.4, 146.4, 153.7, 176.0, 177.6; HRMS (EI): m/z calcd for C9H6N2O2S:

206.0150; found: 206.0144.

5-Methyl-2,3-dihydro-benzo[d]imidazo[2,1-b]thiazole-6,7-dione (7b)

Purple solid; decomposed in 173–177 �C.1H-NMR (CDCl3, 600 MHz) d 2.06 (s, 3H), 3.81 (t, j = 7.7 Hz, 2H), 4.59 (t,

j = 7.7 Hz, 2H), 5.55 (s, 1H); 13C-NMR (DMSO-d6, 150 MHz) d 14.2, 43.7, 62.4,

96.1, 131.5, 146.6, 148.1, 159.8, 175.9, 177.1; HRMS (EI): m/z calcd for C10H8N2O2S:

220.0306; found: 220.0310.

5-Methoxy-2,3-dihydro-benzo[d]imidazo[2,1-b]thiazole-6,7-dione (7c)

Red solid, decomposed in 181–183 �C.1H-NMR (CDCl3, 200 MHz) d 3.82 (t, j = 7.9 Hz, 2H), 4.17 (s, 3H), 4.64 (t,

j = 7.9 Hz, 2H), 5.52 (s, 1H); 13C-NMR (DMSO-d6, 50 MHz) d 43.7, 52.9, 62.4, 96.1,

131.5, 146.6, 148.1, 159.8, 175.9, 177.1; HRMS (EI): m/z calcd for C10H8N2O3S:

236.0255; found: 236.0231.

2,3-Dihydro-benzo[d]imidazo[2,1-b]thiazole-6,7-dione (7f)

Deep red solid; decomposed at 186–188 �C.1H-NMR, (200 MHz, DMSO-d6) d 3.75 (t, j = 7.5 Hz, 2H), 4.47 (t, j = 7.5 Hz,

2H), 5.73 (s, 1H), 6.93 (s, 1H); 13C-NMR (DMSO-d6, 50 MHz) d 43.7, 62.4, 96.0,

131.5, 124.4, 146.6, 148.0, 159.8, 175.9, 177.0; HRMS (EI): m/z calcd for C9H6N2O2S:

206.0150; found: 206.0115.

A. Alizadeh et al.

123

Results and discussion

Initial characterization of the reactions was carried out using a cyclic voltammetry

technique. Cyclic voltammetric responses of a GC electrode to 1 mM catechol (1a,

Scheme 1) in water/acetonitrile (90/10) solution containing 0.2 M sodium acetate in

the absence and presence of 2-imidazolidine thione (3) are outlined in Fig. 2. In this

figure, curve a shows a well-defined oxidative peak (A1) at 0.330 V (vs. SCE)

consistent with the oxidation of 1a to o-benzoquinone (2a). Upon reversal of the

scan direction, a corresponding reduction peak (C1) is observed at 0.27 V, which is

attributed to the back reduction of 2a to the parent catechol. A peak current ratio

(Ip1C/Ip1

A) of nearly unity, especially during the repetitive recycling of the potential

can be observed for 1a in the absence of 3, and this ratio can be considered as a

criterion for the stability of o-benzoquinone generated at the surface of GC

electrode under the applied experimental conditions. Figure 2 curve b shows the

cyclic voltammogram obtained for a 1 mM solution of 1a in the presence of 1 mM

of 3. The voltammogram exhibits one anodic and one decreased cathodic peaks

appearing at 0.33 and 0.22 V versus SCE, respectively. The –SH and –NH groups of

3 are appropriate nucleophiles, so it seems that a Michael 1,4-addition of 3 to

intermediate 2a can proceed in a quick and simple way leading to the considerable

decrease in the height of cathodic peak (C1). As a result, the reactivity of 2a towards

3 can be monitored as a decrease in the height of the cathodic peak C1. The

comparison of C1 peaks in the absence and presence of 3 shows a considerable

decrease of the current density for the latter and this obviously indicates the

reactivity of electrogenerated active o-benzoquinone 2a as Michael-acceptor toward

nucleophile 3 as Michael-donor. The negative shift of the C1 peak observed in curve

b, relative to curve a, is probably due to the formation of a thin film of product at the

surface of the electrode, inhibiting to a certain extent the performance of the

electrode process [21]. Figure 2 curve c shows the cyclic voltammogram obtained

for a 1 mM solution of 3 in the absence of 1a and confirms that 3 is

electrochemically inactive in these conditions.

The preparative electrolysis was performed under potentiostatic condition (CPC)

by oxidation of 1a in the presence of 3 at 0.31 V versus SCE potential on a graphite

rode anode electrode in an undivided cell (more detail is described in the

‘‘Experimental’’ section). The monitoring of electrolysis progress was carried out

using cyclic voltammetry and the related voltammograms are shown in Fig. 3.

Notably, proportional to the advancement of coulometry, A1 decreased and its

corresponding cathodic peak (C1) disappeared when the charge consumption

became about six electrons per molecule of 1a. The positive shift of the A1 peak in

the presence of 3 that was also enhanced during the repetitive recycling of potential

is probably due to the formation of a thin film of product at the surface of the

electrode, inhibiting to a certain extent, the performance of the electrode process

[21, 22] Additionally, during the course of coulometry two new peaks A2 and C2

appeared at 0.16 and 0.12 V, respectively, and the height of these peaks was slightly

increased proportional to the advancement of coulometry, parallel to the decrease in

height of A1 and C1 peaks (Fig. 3). We believe that this A2/C2 redox couple

corresponds to 6a/7a conversion. The peak C2 is presumably due to the compound

Electro-generated ortho-quinoide intermediates

123

7a for which the peak amplitude is increasing with time. On the other hand, the

observation of the oxidation peak A2 may be due to the generation and

accumulation of 6a from the reduction of 7a occurring during the initial polarization

of the electrode from -0.4 to ?0.1 V where 7a is reduced into 6a (see Fig. S-17 in

supporting information).

The aforementioned voltammetry and coulometry results allow us to propose the

pathways shown in Scheme 1 for the electrooxidation of catechol 1a in the presence

of 3. According to our results, it seems that following anodic oxidation of 1a to

N

NH

SH

N

HN

S

R1

OHHO

R1

OHHOH+

N

HN

S

R1

OHO

3

2a-eH+

H

5a-cH+

R2

R1

OO

R2

R2-2 H+, -2e-

4a-c and 4d, 4e

-2 H+, -2e-

7a: 90%; 7b: 89%; 7c: 85%

E

C R2

E

C N

HN

S

O

OR1

R2

N

NS

O

OHR1

R2

H+

NN

S OH

OH

R1-2 H+, -2e-EN

N

S O

O

R1

6a-c

1a-c: R1=H, CH3, OCH3; R2= H

1d: R1=H; R2=CH31e: R1=H; R2= C(CH3)3

ECECE

1 2

345

6

Scheme 1 A schematic representation of possible mechanisms for the electro-oxidation of 1a–e in thepresence of 3 under CPC condition

Fig. 2 Cyclic voltammograms of 1.0 mM 1a in the absence (a) and presence (b) of 1.0 mM of 3 and(c) 1.0 mM of 3 in the absence of 1a at glassy carbon electrode versus SCE in water/acetonitrile (90/10)solution containing 0.2 M sodium acetate. Scan rate: 100 mV/s; t = 25 ± 1 �C

A. Alizadeh et al.

123

intermediate 2a, an intermolecular Michael-type reaction of mercaptide anion 3with 2a occurs and this reaction seems to occur much faster than other side reactions

[23], leading to the formation of intermediate 4a. The oxidation of 4a is easier than

the oxidation of the parent-starting molecule 1a by virtue of the presence of an

electron-donating group. Then, following the oxidation of 4a to 5a, an intramole-

cular Michael-type reaction occurs in a domino fashion to give 6a. This structure

can finally be further oxidized to form 7a through an oxidative/intermolecular

Michael-type addition/oxidative/intramolecular Michael-type addition/oxidative

sequence (ECECE). The current efficiency of this controlled-potential coulometry

was simply calculated using the Faraday’s law and found to be *98.0 % (ECECE

mechanism needs at least six electrons, n = 6 and 6F charge consumption per each

mol of 1a). Under these reaction conditions, a novel nitrogen- and sulfur-containing

heterocycle of type imidazo[2,1-b]thiazole (7a) was obtained purely in excellent

yield and electrochemical efficiency (Table 1, entry 1) and no extra purification was

needed.

With a reliable set of conditions in hand, and in order to investigate the scope and

generality of the developed procedure, we studied the electrochemically-induced

reaction of some other catchols bearing electron-withdrawing or electron-donating

groups at the C-3 or C-4 positions with 3. The electro-oxidation of 3-methycatechol

(1b) and 3-methoxycatechol (1c) in the presence of 3 as a nucleophile in sodium

acetate (0.2 M) proceeded in a way similar to that of 1a. It’s worth mentioning that

the presence of a methyl or a methoxy group at the C-3 position of 1b or 1c may have

subtle electronic or steric effects on the reactivity of their relevant o-bezoquinones

(2b, c) and would probably cause these Michael acceptors to be attacked by 3 at the

C-4 or C-5 positions to yield two types of product in each case (7b/7b0 and 7c/7c0;Fig. 4). Since the methyl and methoxy groups are both electron-donating substit-

uents, we suggest that intermediates 2b and 2c are more electropositive at C-5

position and therefore, can be selectively attacked from C-5 position by the –SH

moiety, finally leading to the formation of 7b and 7c, respectively, and not 7b0 or 7c0.The accuracy of these suggestion could be simply proved by comparing the

calculated [24] and experimentally obtained 1HNMR data of the possible structures

[25, 26] (Table 2). For instance, 1HNMR investigation of the product obtained from

1b ? 3 indicated the presence of one singlet at 5.55 ppm attributed to the hydrogen

on quinone ring [27]. On the other hand, the calculated ppm for the same hydrogen in

structure 7b was 5.97, while for the other suggested structure (7b0) the ppm of singlet

was calculated to be at 6.30. In the case of 1c ? 3, also the same results were

obtained. Comparison of these calculated and experimental data proved that

following their anodic formation, intermediates 2b and 2c were presumably attacked

by –SH moiety of 3 only at C-5 position through an intermolecular Michael-type

reaction, finally leading to the regioselective formation of 7b and 7c as final products.

These sequential reactions led to the formation of novel compounds 7b and 7cthrough the same one-pot five-step ECECE mechanism in excellent yields and

electrochemical efficiencies (Table 1, entries 2, 3).

Interestingly, in contrast to the cases of 1a–c, no heteroannulation reaction was

observed in the electrolysis of 1d and 1e in the presence of 3 under the same

experimental condition, and these catechols were isolated back from the reaction

Electro-generated ortho-quinoide intermediates

123

mixture after several hours electrolysis (Table 1, entries 4 and 5). To explain these

exceptional behavior observed for 1d and 1e, one can only assume that although the

oxidation of 1d or 1e is easier than the oxidation of 1a by virtue of the presence of

an electron-donating group; however, the presence of a methyl or tert-butyl group at

the C-4 position of 2d or 2e would presumably cause a steric inhibition of the

accessibility of neighbor electrophilic b-position to nucleophilic attack of 3 and, as a

result, there may not be possibility for the subsequent Michael-type addition of 3 to

form 4d or 4e (Scheme 1).

On the other hand, oxidation of 3,4-dihydroxybenzoic acid (1f) with an electron-

withdrawing group at the C-4 position, in the presence of 3 proceeds in a nearly

different manner than that of 1a–c, 1d and 1e. Our spectroscopic results (NMR and

Mass) showed that electrooxidation of 1f to 2f (Scheme 2), and subsequent

regioselective intermolecular Michael addition reaction of 3 with 2f at its most

electropositive position (C-5), leads to adduct 4f which is capable of undergoing

further oxidation to afford intermediate 5f. An intramolecular 1, 4-addition

(Michael) reaction in 5f followed by an electro-decarboxylation process [28] can

lead to the final product (7f) (Table 1, entry 6). As can be seen, this unique

sequential heteroannulation reaction of 1f with 3 leads to the same product (7a)

obtained from the reaction of 1a and 3, but through different mechanistic fashion

ECECCE. The overall reaction is presented in Scheme 2.

Finally, electrolysis of the catechols (1a–f) in the presence of 3 was also investigated

under controlled-current coulometry (CCC) conditions with carbon anode and iron

cathode at 25 mA, (current density = 5 mA/cm2). The current density 5 mA/cm2

(I = 25 mA, electrodes surface 5 cm2) was found to be optimal for the electrooxidation

Fig. 3 Cyclic voltammogerams of 1.0 mmol of 1a in the presence of 1.0 mmol of 3 in sodium acetate(0.2 M) and at a glassy carbon electrode during controlled-potential coulometry: a at the beginning, b inthe course, and c at the end of coulometry. Scan rate 100 mV/s; T = 25 ± 1 �C. d Variation of peakcurrent IpA1 versus charge consumed

A. Alizadeh et al.

123

Tab

le1

Contr

oll

ed-p

ote

nti

alel

ectr

oly

sis

of

cate

chols

(1a–

f)in

the

pre

sen

ceo

f2

-im

idaz

oli

din

eth

ion

e(3

)

En

try

E(V

)C

atec

ho

lP

rod

uct

10

.31

OH

OH

1a 1

aN

N

SO O

H7a

7a

20

.30

OH

OH

CH

3

1b

1b

NN

SO O

CH

3

7b

30

.30

OH

OH

OC

H3

1c

1c

NN

SO O

OC

H3

7c 7

c

40

.28

OH

OH

H

H3C

1d

1d

7d

Electro-generated ortho-quinoide intermediates

123

Tab

le1

con

tin

ued

En

try

E(V

)C

atec

ho

lP

rodu

ct

50

.28

OH

OH

H

CH

3CH3C

CH

3

1e

1e

7e

60

.35

OH

OH

CH

O

O

1f

1f

NN

SO O

H 7

f

7f

En

try

Tim

e(h

)C

E(%

)aY

ield

(%)b

Mec

han

ism

16

98

.09

0.7

EC

EC

E

26

.59

4.3

89

.6E

CE

CE

37

93

.38

5.2

EC

EC

E

47

–N

.R.c

–

57

–N

.R.c

–

66

95

85

.4E

CE

CC

E

aC

urr

ent

effi

cien

cyca

lcu

late

du

sin

gth

eF

arad

ay’s

law

bIs

ola

ted

yie

lds

cN

ore

acti

on

occ

urr

edan

du

nre

acte

dst

arti

ng

mat

eria

lsw

ere

re-i

sola

ted

A. Alizadeh et al.

123

of catechols in the presence of 3 (Table 3). The increase of current density up to 50 mA/

cm2 (I = 250 mA) results in a slight decrease of the reaction yield, which may be

connected with the activation of undesired direct electrochemical processes possible

under these conditions, leading to oligomerization of starting materials or active

intermediates. Furthermore, a decrease in the current density to 2 mA/cm2

(I = 10 mA) led to the decrease in both the current and the substance reaction yields,

more likely due to the insufficient initiation of the electrochemical reaction in this case

[29]. As seen again, under CCC condition, while the electrolysis of a solution containing

f2f1

N

HN

S

H

OHHO

H

OHHO

H

OO

5f H+

COOH COOH

-2 H+, -2e-

4f

3E

COOHN

HN

S

O

OH

HOOC

N

NS

O

OHHHOOC

H+

NN

S OH

OH

R1

NN

S O

O

R1

- CO2

6f

-2 H+, -2e-

7f: 85%

45

12

36

E

C

C

C

-2 H+, -2e-E

ECECCE

Scheme 2 A schematic representation of possible mechanism for the anodic oxidation of 1f in thepresence of 3 under CPC condition

NN

S O

O

CH3

NN

S O

O

OCH3

H H

NN

S

O

O

CH3

NN

S

O

O

OCH3

H H

or or

7'b7b7 c 7c'

Fig. 4 The two types of possible product from the elctrooxidation of 1b or 1c in the presence of 3

Table 2 Experimental and

calculated 1H NMR data

obtained for possible structures

(7b/7b0 and 7c/7c0)

Compound Experimental

d (ppm)

Calculated

d (ppm)

Product obtained from 1b 5.55

7b 5.97

7b0 6.30

Product obtained from 1c 5.53

7c 5.97

7c0 6.30

Electro-generated ortho-quinoide intermediates

123

of 1 mmol of 1a–c and 1f in the presence of 3 led to the formation of 7a–c and 7f as final

products (Table 3, entries 1–3 and 6), the electrolysis of 1d and 1e had no final product

(Table 3, entries 4 and 5). Although, employing both CPC and CCC techniques made it

possible to obtain the same products; however, the CCC was found to be a faster

procedure but the electrochemical and isolated yields of the products were higher in

CPC condition.

Conclusion

In conclusion, we have described a convenient, environmentally friendly and

chemical oxidant-free protocol for the preparation of a series of novel polycyclic

imidazo[2,1-b]thiazoles through a domino reaction of commercially available starting

materials and easily accessible quinoide intermediate in ambient condition with high

atom economy. Besides the high electrochemical efficiency and atom economy as a

domino process, this reaction has the advantages of: (1) the starting materials are

readily available and the reagents are cheap; (2) the reaction proceeds smoothly under

very mild conditions without introducing any acid, base or metal catalyst; and (3) it is

an environmentally benign transformation due to the fact that only electrons are used

as reagent instead of oxidative ones. We believe that this simple electrooxidative

coupling reaction with its advantages of complementary reactivity and mild reaction

conditions, and especially dramatically technical feasibility can compliment the

existing chemical strategies. In addition, we hope that, because of the diversity of this

method, it can be adopted in organic heterocyclic chemistry to synthesize and screen

libraries of related biologically important imidazothiazoles.

Acknowledgments Financial support for this work from Research Affairs, Razi University, Kerman-

shah, Iran is gratefully acknowledged. We also thank Professor M.S. Workentin (Department of

Chemistry, UWO, Canada) for the use of the HRMS spectrometer.

Table 3 Controlled-current coulometry of catechols (1a–f) in the presence of 2-imidazolidine thione (3)

Entry I (mA) Current density

(mA/cm2)

Catechol Product Time

(min)

CE

(%)aYield

(%)b

1 25 5 1a 7a 12 90 82

2 25 5 1b 7b 11 92 89

3 25 5 1c 7c 14 90.2 76

4 25 5 1d – 40 – N.R.c

5 25 5 1e – 40 – N.R.c

6 25 5 1f 7f 26 89 80

a Current efficiency calculated using the Faraday’s lawb Isolated yieldsc No reaction occurred and unreacted starting materials were re-isolated

A. Alizadeh et al.

123

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