"Metal-Free" Nanoassemblies of AIEE-ICT-Active Pyrazine Derivative: Efficient Photoredox System for the Synthesis of Benzimidazoles

Shruti Dadwal, Manoj Kumar, and Vandana Bhalla*

Article

“

Metal-Free” Nanoassemblies of AIEE-ICT-Active Pyrazine

Derivative: Eﬃcient Photoredox System for the Synthesis of

Benzimidazoles

Cite This: https://dx.doi.org/10.1021/acs.joc.0c01965

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sı Supporting Information

ABSTRACT: Supramolecular nanoassemblies of an AIEE-ICT-

active pyrazine derivative (TETPY) having strong absorption in

the visible region and excellent transportability have been utilized as

an eﬃcient photoredox catalytic system for the synthesis of a variety

of benzimidazoles having electron-withdrawing/electron-releasing/

aliphatic groups under “metal-free” conditions. The reaction

protocol involves the successful harvesting of visible light by

TETPY assemblies to catalyze the coupling of o-phenylenediamine/

substituted diamines and substituted aromatic/heterocyclic/aliphatic

aldehydes under aerial conditions using mixed aqueous media as the

reaction solvent. TETPY assemblies could activate aerial oxygen to

generate superoxide for completing the vital proton abstraction step

without the need for any external metal/base/oxidant. Moreover, all

the products are puriﬁed by recrystallization from organic solvents.

The TETPY assemblies also exhibited high eﬃciency in catalyzing the synthesis of 2-substituted benzothiazoles and quinazolines in

excellent yields.

INTRODUCTION

toluene, and ethyl acetate) as reaction media, inert

atmospheric conditions, requirement of additional ligands,

and prolonged heating of the reaction mixture at high

temperature. To get rid of the problems associated with

■

Benzimidazoles are well-known structural motifs for the

preparation of building blocks having widespread applications

in material, medicinal, and supramolecular chemistry.

−3

The

11,24,25

thermal heating, a variety of metal-based

and organic

enormous utilization of benzimidazoles in diverse ﬁelds

provides suﬃcient impetus to develop facile synthetic

protocols to meet the demand−supply balance. Among

diﬀerent synthetic approaches explored, transition-metal-

catalyzed condensation of readily available o-phenylenediamine

and aldehydes/alcohols is a convenient route to attaining these

26,27

dye-based

photoredox catalytic systems and catalyst-free

have been developed; unfortunately, most of these

28,29

systems

reported systems could not overcome the limitations such as

requirement of organic solvents as reaction media, demand of

high catalytic loading, longer reaction time, high energy source

of radiation, and tedious puriﬁcation methods. Furthermore,

structural modiﬁcations of organic dyes to enhance their

eﬃciency as “metal-free” photoredox catalysts involve diﬃcult

synthetic procedures. In an eﬀort to avoid the need for

structural modiﬁcation, very recently, unmodiﬁed ﬂuorescein

has been used as a photocatalytic system for the synthesis of

benzimidazoles in organic media using a blue LED as the

derivatives. Over the past few years, to widen the substrate

scope, to restrict the formation of side products, and to

improve the yield of the target compounds, a variety of

methodologies such as ionic liquid-promoted benzimidazole

synthesis, utilization of additional oxidants, molecular iodine-

assisted synthesis of benzimidazoles under alkaline conditions,

cobalt-catalyzed synthesis of benzimidazoles through dehydro-

genative coupling of aromatic diamines and alcohals, and

source of radiation (Scheme 1).

reduced graphene oxide-catalyzed synthesis of benzimida-

zoles have been developed. Besides these methodologies,

Received: August 14, 2020

several other catalytic systems have been developed for the

synthesis of benzimidazoles.

11−23

Although these reported

methodologies are eﬃcient with respect to substrate scope and

yields, these are not impressive in terms of cost and

environmental safety aspects due to the requirement of bases

in stoichiometric amounts, organic solvents (dioxane, THF,

XXXX American Chemical Society

J. Org. Chem. XXXX, XXX, XXX−XXX

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Article

Scheme 1. Comparison of Previous and Present Protocols for the Synthesis of 2-Benzimidazoles

Scheme 2. Possible Mechanistic Pathway for the Synthesis of Benzimidazoles

Pathway 1: PET from intermediate A to O . Pathway 2: PET from intermediate A to the photocatalyst (PC).

Although the requirement of high energy radiation and

organic solvents for acceleration of the reaction is not cost-

eﬀective and eco-friendly, the approach is inspiring. This study

motivated us to develop a “metal-free” easy-to-synthesize

photocatalytic system that could work eﬃciently under mild

reaction conditions such as low-energy visible light irradiation,

mixed aqueous media, low catalytic loading, and air as an

oxidant.

A look at the mechanistic cycle proposed on the basis of

literature reports in the case of photocatalyzed reactions

between diamines and aldehydes showed that the in situ

generation of radical cation intermediate B through the

oxidation of intermediate A is a vital preliminary step as

shown in Scheme 2. For the feasibility of the next reaction

steps (deprotonation, proton abstraction, etc.) under base/

inert atmosphere/additional oxidant-free conditions, in situ

generation of reactive oxygen species (superoxide species)

through reduction of aerial oxygen is a prerequisite.

Based on our preliminary investigation and proposed

mechanistic cycle (Scheme 2), to catalyze the synthesis of

benzimidazoles under metal/base/oxidant/inert atmosphere-

free conditions, the hypothesized photocatalyst aside from

having strong absorption in the visible region should also have

good transportability and reduction potential to assist the

electron transfer for the generation of intermediate B and for

the reduction of aerial oxygen (Scheme 2, pathway 2).

Recently, from our lab, we reported the preparation of a

pyrazine-based donor−acceptor system (TETPY, Figure 1),

which exhibited high eﬃciency in various oxidative organic

transformations facilitated by in situ generation of reactive

oxygen species (ROS).

The nanoassemblies of TETPY exhibited suﬃcient reduc-

tion potential to generate superoxide species from molecular

oxygen under visible light irradiation in mixed aqueous media.

In view of the favorable properties of TETPY, we examined the

catalytic eﬃciency of the nanoassemblies of TETPY for the

synthesis of benzimidazoles under “metal/base/additive/

argon-free” conditions in mixed aqueous media using visible

light at room temperature.

As part of our initial investigation, we explored the

possibility of activation of aerial oxygen by intermediate A

through a photoinduced electron transfer (PET) process. We

calculated the free energy change (−ΔG ) for this step from

The test reaction proceeded very well at 0.1 mol % catalytic

loading of nanoassemblies of TETPY and furnished the ﬁnal

product in an excellent yield of 96%. We further examined the

potential of the nanoassemblies of TETPY to catalyze the

reaction between o-phenylenediamine/substituted diamines

and a variety of aliphatic/heterocyclic/aromatic aldehydes

bearing electron-withdrawing/electron-releasing groups. To

30,31

the available literature data,

and the value comes out to be

.24 eV (Scheme 2, pathway 1). Surprisingly, despite the

decently favorable ΔG value, the insigniﬁcant progress of the

reaction observed under “catalyst-free” conditions may be

attributed to very weak absorption of reactants and

intermediate A in the visible region (vide infra).

The Journal of Organic Chemistry

J. Org. Chem. XXXX, XXX, XXX−XXX

Article

RESULTS AND DISCUSSION

■

Photophysical Properties of TETPY. The derivative

TETPY is synthesized by Suzuki−Miyaura coupling following

the procedure reported in the literature. The donor−

acceptor TETPY system showed strong absorption in the

visible region and formed supramolecular nanoassemblies in

mixed aqueous media due to its intramolecular charge transfer

(

ICT) and aggregation-induced emission enhancement

AIEE) characteristics as already reported. The nano-

assemblies of TETPY showed good photostability under

continuous irradiation of visible light for 36 h. Furthermore,

due to the suﬃcient ground-state reduction potential (−1.76

V), the donor−acceptor-based TETPY system exhibited high

potential to reduce molecular oxygen (E = −0.89 V) to

generate superoxide species.

Figure 1. Structure of the pyrazine-based donor−acceptor system

TETPY.

red

VISIBLE LIGHT-INDUCED PHOTOCATALYTIC

SYNTHESIS OF 2-BENZIMIDAZOLES

our pleasure, all the reactions worked well to furnish the

desired products in good to excellent yields with high TONs

and TOFs. In comparison to other reported catalytic systems,

TETPY nanoassemblies exhibited high catalytic eﬃciency to

synthesize 2-substituted benzimidazoles under mild reaction

conditions such as mixed aqueous media, visible light

irradiation, room temperature, and air using molecular oxygen

as the sole oxidant (Table S1, Supporting Information).

Interestingly, TETPY nanoassemblies also exhibited high

eﬃciency in catalyzing the synthesis of 2-benzothiazoles with

a good substrate scope. Further, the photoredox catalytic

system also exhibited high eﬃciency for the gram-scale

synthesis of benzimidazole/benzothiazole. The eﬃciency of

TETPY nanoassemblies has also been demonstrated for the

preparation of 2-substituted quinazolines. Unprecedentedly,

this report reveals the potential of TETPY assemblies in

photocatalyzing the synthesis of 2-benzimidazole/benzothia-

zole/quinazolines under “metal/oxidant/inert atmosphere-

free” conditions in mixed aqueous media.

■

For the initial optimization, we examined the coupling of o-

phenylenediamine (1a) with benzaldehyde (2a) in EtOH as

the reaction media in the presence of the isolated form of

TETPY as a photocatalyst under visible light irradiation using

air as an oxidant. The reaction gave the desired product in 80%

yield (Table 1, entry 1). Interestingly, upon switching the

isolated form of TETPY with the as-prepared assembled form,

the desired product was furnished in 96% yield using mixed

aqueous media (EtOH/H O, 1:1) (Table 1, entry 2), which

may be attributed to the potential of TETPY assemblies to

generate ROS more eﬃciently in mixed aqueous media.

Further, we believe that the carbonyl oxygen of aldehyde (2a)

and NH hydrogen of o-phenylenediamine (1a) are activated

in the presence of water as the co-solvent through cooperative

hydrogen bonding. These studies clearly indicate the

importance of TETPY nanoassemblies as the photocatalyst.

To understand the inﬂuence of the intensity of light irradiation

Table 1. Optimizations of the Reaction Conditions for the Synthesis of 2-Benzimidazoles

entry

photocatalyst (nanoassemblies)

additive/base

solvent

time (h)

yield (%)

TETPY

EtOH

EtOH/H O (1:1)

DMSO/H O (1:1)

1.5

traces

THF

ACN

DMF

MeOH

H O

Na CO as base

EtOH/H O (1:1)

TETPY

EtOH/H O (1:1)

Reaction conditions (unless otherwise noted): 1a (0.5 mmol), 2a (0.5 mmol), solvent (2 mL), assemblies of TETPY (4.0 mg of TETPY dissolved

in 800 μL of DMSO and 1200 μL of distilled water). The resulting solution (500 μL) was used as the photocatalyst for each reaction: 16 W white

LED as the irradiation source, room temperature, 2 h, in aerial conditions. Isolated form of TETPY (1 mg). 5W blue LED as source of

irradiation; Dark. Inert atmosphere. Reaction condition: 1a (0.5 mmol) and 2a (1 mmol).

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Table 2. Substrate Scope for the Synthesis of 2-Benzimidazoles Using Supramolecular Nanoassemblies of TETPY

The moles of 2-substituted benzimidazole formed per unit catalyst. The rate of formation of 2-substituted benzimidazole per unit catalyst per

unit time (2 h).

on the reaction, we examined the model reaction using a blue

LED as the source of irradiation. The desired product was

obtained in 96% yield in 1.5 h (Table 1, entry 3). Although the

reaction time was shortened, we preferred “more green” low-

energy white light irradiation for carrying out further reactions.

The eﬀect of the other solvents such as DMSO/H O, THF,

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Scheme 3. Proposed Reaction Mechanism for the Synthesis of 2-Benzimidazoles/Benzothiazoles Using Supramolecular

Nanoassemblies of TETPY

ACN, DMF, MeOH, and H O were also examined in the

we explored the substrate scope of the condensation of o-

phenylenediamine (1a)/substituted diamines (1b−d) with

regard to various substituted aldehydes (2a−v) bearing

aliphatic, aromatic, and heterocyclic groups using supra-

molecular assemblies of TETPY as the catalytic system

model reaction using supramolecular nanoassemblies of

TETPY as the photocatalyst (Table 1, entries 4−9). All

these studies clearly show that in the presence of polar protic

solvents except in the case of H O, the desired product is

obtained in higher yield. The insolubility of the reactants in

aqueous medium may be the reason behind the insigniﬁcant

(

Table 2).

The aromatic aldehydes bearing electron-withdrawing/

donating groups were allowed to react, and the desired

products were furnished in excellent yield (Table 2, products

progress of the reaction in H O. Based upon these

optimization experiments, EtOH/H O (1:1) was chosen as

the reaction solvent for the preparation of benzimidazole

derivatives. Next, we examined the role of the presence/

absence of a base on the yield/kinetics of the reaction under

the optimized reaction conditions; the product was obtained in

traces, which clearly shows the insigniﬁcant role of the base in

catalyzing the synthesis of 2-benzimidazoles (Table 1, entry

b−n). Next, we examined the catalytic eﬃciency of TETPY in

a reaction involving aliphatic aldehydes such as formaldehyde

2o) and acetaldehyde (2p) as one of the coupling partners,

and the desired benzimidazoles were obtained in good yields

Table 2, products 3o−p). Substituted diamines (1b−d)

(

irrespective of the substitution on them were also found to be

reactive with aromatic/aliphatic aldehydes and gave the desired

products in excellent yield (Table 2, products 3p, 3t, and 3u).

Next, the catalytic eﬃciency of TETPY assemblies in reaction

with regard to heterocyclic aldehydes such as furfuraldehdye

0). To understand the contribution of each reaction

condition, i.e., visible light irradiation, assemblies of TETPY,

and air, toward the progress of the reaction, we performed

diﬀerent control experiments. In the ﬁrst control reaction, the

model reaction between 1a and 2a was allowed to proceed in

the dark in the presence of nanoassemblies of TETPY, and the

desired product was obtained in traces. Next, upon irradiating

the reaction mixture in the absence of assemblies of TETPY,

the desired product was again obtained in traces. When the

model reaction was repeated under inert atmosphere

conditions, the formation of the desired product was detected

in traces. All these experiments demonstrate the importance of

assemblies of TETPY, visible light irradiation, and aerial

conditions for the synthesis of 2-benzimidazoles (Table 1,

entries 11−13). To ascertain the product selectivity of the

TETPY-catalyzed system in terms of formation of 2-

substituted/1,2-disubstituted benzimidazoles, the control ex-

periment was performed using higher equivalents (1 mmol) of

the benzaldehyde (2a) under the optimized reaction

conditions (Table 1, entry 14). The formation of 1,2-

disubstituted benzimidazole was not detected even in traces,

which conﬁrms the high selectivity of the supramolecular

nanoassemblies of TETPY for the preparation of monosub-

stituted benzimidazoles. In the next part of the investigation,

(

2q), 2-thienylcarboxaldehyde (2r), and 3-thienylcarboxalde-

hyde (2s) was also explored and the desired benzimidazoles

were furnished in over 85% yields (Table 2, products 3q−s).

Ferrocene-2-carboxaldehyde (2v) also proved as a successful

partner for the synthesis of ferrocene-substituted benzimida-

zole (Table 2, product 3v). In general, all the aliphatic/

heterocyclic/aromatic aldehydes bearing electron-withdraw-

ing/releasing groups furnished the desired benzimidazoles

derivatives in good to excellent yields. However, the aldehydes

having electron-withdrawing groups furnished the desired

product in a slightly higher yield. Since the ﬁrst step of the

reaction involves the nucleophilic attack of diamines on the

aldehydes, we believe that in the case of the electron deﬁcient

aldehydes, the nucleophilic attack is more favored. All the

products (Table 2, products 3a−v) were puriﬁed by

recrystallization. The calculated TONs and TOFs for all the

synthesized 2-benzimidazoles are quite high, which support the

excellent eﬃciency of the supramolecular nanoassemblies of

TETPY in these reactions.

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Mechanistic Studies. Various control reactions clearly

highlighted the important role of visible light irradiation, aerial

conditions, and TETPY assemblies in the completion of the

reaction in a short reaction time and high product yield. To

understand it further, we monitored the model reaction using

absorption spectroscopy. The UV−vis spectra of o-phenyl-

enediamine (1a) and benzaldehyde (2a) did not show

absorption in the visible region; however, an absorption

band appeared at 368 nm after irradiating the reaction mixture

for 20 min (Figure S1, Supporting Information). Since the

aminothiophenol (4) and benzaldehyde (2a) under visible

light irradiation using supramolecular nanoassemblies of

TETPY in EtOH/H O (1:1) as the reaction media, and

interestingly, the desired benzothiazole product was furnished

in 97% yield in 40 min (Table 3, entry 1). On the other hand,

Table 3. Optimization Reaction Conditions for the

Synthesis of 2-Benzothiazoles

target compound (3a) absorbs at 318 nm, this study

conﬁrms that the reaction proceeds through intermediate A

having absorption in the visible region (368 nm). Further, the

value of free energy change (−ΔG ) for the electron transfer

photocatalyst

(Assemblies)

time

yield

(%)

from intermediate A to TETPY assemblies (Scheme 3) comes

out to be 1.37 eV which conﬁrms the spontaneity of the

process (detailed calculations in the Supporting Informa-

entry

solvent

(min)

TETPY

EtOH/H O (1:1)

EtOH

0,32

tion).

On the basis of these results, we propose that the

DMSO/H O (1:1)

ﬁrst step of the reaction involves the condensation of reactants

to form an imine derivative and generation of photoexcited

TETPY* species upon irradiating the reaction mixture.

Further, intramolecular cyclization of the imine derivative led

to the generation of intermediate A, which serves as an

electron donor and transfers an electron to TETPY*

MeOH

ACN

H O

DMF

THF

EtOH/H O (1:1)

traces

·−

assemblies to generate TETPY , which in turn activates the

oxygen to furnish superoxide species before returning to the

ground state. Subsequently, the oxidation of intermediate A

results in the formation of intermediate B. In the next step, the

deprotonation of intermediate B by superoxide radical anion

species generates species C, which after hydrogen abstraction

by hydroperoxyl radical furnishes the ﬁnal product (Scheme

TETPY

EtOH/H O (1:1)

Reaction conditions (unless otherwise noted): 4 (0.5 mmol), 2a (0.5

mmol), solvent (2 mL), TETPY (0.1 mol %, 4.0 mg of TETPY

dissolved in 800 μL of DMSO and 1200 μL of distilled water). The

resulting solution (500 μL) was used as the photocatalyst for each

reaction: 16 W white LED as the irradiation source, room

temperature, 40 min, in aerial conditions. Isolated form of TETPY

). The potential of TETPY assemblies to transfer a single

(

1 mg). Dark. Inert atmosphere.

electron was conﬁrmed by their absorption studies in the

presence of methyl viologen (MV ) as the acceptor and

triethanolamine (TEOA) as the sacriﬁcial donor. The

absorption studies indicated the presence of the reduced

form of methyl viologen, which is attributed to the transfer of

electrons from the sacriﬁcial donor (TEOA) to the acceptor

while repeating the same reaction using TETPY in its isolated

form using EtOH as the reaction media, the target product was

obtained in 80% yield after 40 min (Table 3, entry 2). We also

examined the model reaction using diﬀerent solvents such as

DMSO/H O, MeOH, ACN, H O, DMF, and THF (Table 3,

entries 3−8), and the highest eﬃciency was observed in the

presence of EtOH/H O (1:1) as the reaction media. In the

(

MV ) by TETPY assemblies (Figure S2, Supporting

Information).

The in situ generation of superoxide species by TETPY

assemblies was also supported by absorption studies using

N,N,N′,N′-tetramethyl-p-phenylenediamine (TMPD) as an

optimization reaction, when the model reaction was carried out

in the absence of supramolecular assemblies of TETPY, the

product was obtained in traces. The formation of products was

also not observed in the absence of light and inert atmospheric

conditions (Table 3, entries 9−11). These optimization

experiments highlight the prudent role of supramolecular

assemblies of TETPY, visible light irradiation, and aerial

oxygen in the synthesis of 2-benzothiazoles. To widen the

substrate scope of the reaction with this protocol, several

aromatic/aliphatic aldehydes (2a−m, 2w, 2y, 2o) were allowed

to react with o-aminothiophenol (4) under optimized reaction

conditions (Table 4).

In the case of substituted benzaldehydes having electron-

withdrawing/donating groups, the desired products were

furnished in good to excellent yields with excellent TONs

and TOFs (Table 4, products 5b−m, 5w, 5x). The catalytic

eﬃciency of TETPY assemblies is also found to be excellent in

the case of aliphatic aldehyde, and the desired product is

obtained in very good yield (Table 4, product 5o). All the

products (Table 4, products 5a−m, 5w, 5x, 5o) were puriﬁed

by column chromatography. We also examined the catalytic

eﬃciency of TETPY assemblies for catalyzing the reaction at

indicator. The studies suggest the TMPD oxidation and

formation of radical cations of TMPD mediated by in situ

release of superoxide species (Figure S3, Supporting

Information). In this reaction mechanism (Scheme 3), the

generation of H O as the side product is conﬁrmed by

iodometric experiments (Figures S4 and S5, Supporting

Information).

Unfortunately, all our attempts to isolate the intermediate A

under lab conditions failed due to its high reactivity. We

believe that the high transport ability and suﬃcient reduction

potential of TETPY assemblies in the ground state contributed

signiﬁcantly toward catalyzing the progress of the reaction in a

much shorter time to furnish the target products in high yields.

VISIBLE LIGHT-INDUCED PHOTOCATALYTIC

SYNTHESIS OF 2-BENZOTHIAZOLES

■

Encouraged by the high photoredox catalytic activity of

assemblies of TETPY for the synthesis of 2-benzimidazoles,

we planned to examine their potential in the synthesis of 2-

benzothiazoles. The model reaction was carried out between o-

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Table 4. Substrate Scope for the Synthesis of 2-Benzothiazoles Using Supramolecular Nanoassemblies of TETPY

Moles of 2-substituted benzothiazole formed per unit catalyst. Rate of formation of 2-substituted benzothiazole per mole catalyst per unit time

(40 min). 4 (1 mmol).

two sites simultaneously. Terephthalaldehdye (2y) was chosen

product through formation of superoxide species as proposed

in Scheme 3.

as the reacting partner, and the desired product (1,4-

diphenylbenzothiazole) was furnished in 95% yield under

optimized reaction conditions (Table 4, product 5y). The

product 5y was puriﬁed by crystallization.

To conﬁrm the formation of intermediate D, we monitored

the reaction using FT-IR spectroscopy. The model reaction

was performed using optimized reaction conditions under an

inert atmosphere, and after 20 min, a peak corresponding to

Mechanistic Studies. Literature reports showed the

synthesis of benzothiazole in low yield (23%) in the absence

of the photocatalyst through photoinduced electron transfer

−

N−H stretching appeared at 2950 cm in the FT-IR

spectrum. The FT-IR spectrum of the ﬁnal product (5a)

−

did not show the presence of any peak at 2950 cm , which

conﬁrmed the formation of intermediate D during the reaction

process (Figure S6 , Supporting Information). The generation

of H O in the proposed reaction pathway (Scheme 3) is

from intermediate D to aerial oxygen. On the other hand, the

presence of supramolecular TETPY nanoassemblies has a huge

impact on the reaction rate due to their excellent trans-

portability to form desired benzothiazole products in excellent

yield in a shorter time.

conﬁrmed by iodometric and KI/CH COOH experimental

35a,37

tests (Figures S7 and S8 , Supporting Information).

We believe that the reaction proceeds through the formation

of intermediate D after the condensation of reactants.

Generation of intermediate E is facilitated by intermediate D

as well as photoexcited TETPY* assemblies through a

photoinduced electron transfer process. Subsequently, supra-

molecular TETPY assemblies assisted the deprotonation and

proton abstraction of intermediate F to furnish the ﬁnal

GRAM-SCALE SYNTHESIS OF 3A AND 5A

■

Further, to check the potential of the assemblies of TETPY,

the photocatalytic reaction for the synthesis of benzimidazole

(3a) and benzothiazole (5a) was repeated using gram-scale

(1.5 g) of the reactants under optimized reaction conditions.

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To our delight, the ﬁnal products 3a and 5a were furnished

in 80 and 82% yields (Scheme 4). The product 3a was isolated

Table 5. Optimization Reaction Conditions for the

Synthesis of Quinazolines

Scheme 4. Gram-Scale Photocatalytic Synthesis of 2-

Benzimidazole (3a) and 2-Benzothiazole (5a) Using

Supramolecular Nanoassemblies of TETPY

photocatalyst

(assemblies)

time

(h)

yield

(%)

entry

solvent

base

TETPY

EtOH/H O (1:1)

traces

EtOH/H O (1:1)

NEt₃

EtOH

EtOH/H O (1:1)

TETPY

EtOH/H O (1:1)

Reaction conditions (unless otherwise noted): 6 (0.5 mmol), 2a (0.5

mmol), solvent (2 mL), TETPY (0.1 mol %, 4.0 mg of TETPY

dissolved in 800 μL of DMSO and 1200 μL of distilled water). The

resulting solution (500 μL) was used as the photocatalyst for each

reaction: 16 W white LED as the radiation source, room temperature,

by a recrystallization process, and the product 5a was isolated

by column chromatography. Therefore, the catalytic system

works well for the synthesis of benzimidazoles and

benzothiazoles on a gram scale.

5 h, in aerial conditions. Isolated form of TETPY (1 mg). Dark.

Inert atmosphere.

between 2-aminobenzylamine (6) and benzaldehyde (2a) in

VISIBLE LIGHT-INDUCED PHOTOCATALYTIC

SYNTHESIS OF 2-SUBSTITUTED QUINAZOLINES

■

EtOH/H O as the solvent media (Scheme 5). After 2 h,

intermediate 8a was obtained in 85% yield and was subjected

Encouraged by the high eﬃciency of the assemblies of TETPY

in catalyzing the condensation of various aromatic/aliphatic

aldehydes with substituted diamines (1a−d)/o-aminothiophe-

nol (4), we planned to examine the potential of the catalytic

system for the synthesis of 2-substituted quinazolines. Earlier,

to further reaction by adding NEt (2 equiv) and supra-

molecular nanoassemblies of TETPY. Finally, the product 7a

was observed in 93% yield. This experiment conﬁrmed the in

situ formation of intermediate 8a as a condensation product of

2-aminobenzylamine (6) and benzaldehyde (2a).

On the basis of these observations, the mechanistic cycle for

the synthesis of quinazolines is proposed as shown in Scheme

6. The ﬁrst step involves the condensation of 2-aminobenzyl-

amine (6) and benzaldehyde (2a) to form 2-phenyl-1,2,3,4-

38b,c

base-promoted metal-free /metal-based,

cially available dye

and commer-

39a,b

-based catalytic systems have been used

for the synthesis of quinazolines with good yields but the

requirement of a longer reaction time and thermal heating is

still a limitation.

For the model reaction, we chose 2-aminobenzylamine (6)

and benzaldehyde (2a) as coupling partners in EtOH/H O

solvent media under the same optimization conditions of

benzimidazoles and benzothiazoles in the presence of nano-

assemblies of TETPY for 15 h. To our delight, the product was

obtained in 70% yield (Table 5, entry 1). Further, the role of

tetrahydroquinazoline (8a). With the help of NEt , 8a was

deprotonated to generate intermediate G, which transfers the

electron to the TETPY system and gives intermediate H and

−

·−

TETPY . Subsequently, TETPY transfers the electron to

molecular oxygen to give superoxide radical anion (O₂^·

−

)

before returning to the ground state. The formed intermediate

H gave intermediate I after the deprotonation step and H O

NEt as the base was checked based on the kinetics of the

as a side product. Subsequently, after similar steps,

intermediate I gave the target product. The in situ formation

of H O was conﬁrmed by iodometric experiments (Figure S9,

reaction, and it was observed that upon using 2 equiv of the

base, the yield of the ﬁnal product was furnished in 93% yield

Table 5, entry 2). The reaction eﬃciency was also determined

35a

(

Supporting Information).

with the isolated form of TETPY, and the product was

obtained in 80% yield (Table 5, entry 3). The model reaction

was allowed to proceed in the absence of visible light and

assemblies of TETPY and under inert reaction conditions

CONCLUSIONS

■

To sum up, AIEE-ICT-active TETPY assemblies exhibited

excellent potential for photocatalyzing the synthesis of 2-

benzimidazoles/benzothiazoles/quinazolines under aerial con-

ditions in mixed aqueous media. Due to their suﬃcient

ground-state reduction potential and good transportation

ability, TETPY assemblies could eﬃciently generate vital

reaction intermediates without requiring any additional

oxidant. Moreover, all the products were obtained in high

yield and their puriﬁcation was not troublesome.

(Table 5, entries 4−6). In all the cases, the desired product was

obtained in traces, which highlighted the role of visible light,

nanoassemblies of TETPY, and aerial conditions. In a nutshell,

for the successful transformation to quinazolines, the presence

of a light source, nanoassemblies of TETPY, aerial conditions,

and presence of a base are necessary. After the optimization of

the reaction conditions for the photocatalytic synthesis of

quinazolines, we explored the eﬃciency of the catalyst with a

range of substituted aldehydes. In all the cases, the desired

products (Table 6, products 7a−d) were obtained in excellent

yields.

EXPERIMENTAL SECTION

General Experimental Methods and Materials. All the

reagents/chemicals were purchased from Aldrich and were used

without any further puriﬁcation. HPLC-grade solvents were used in

UV−vis experimental studies. UV−vis spectra were recorded on a

■

Mechanistic Studies. To gain insight into the mechanism,

control experiments were performed by setting up the reaction

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

Table 6. Substrate Scope for the Synthesis of 2-Quinazolines Using Supramolecular Nanoassemblies of TETPY

Moles of quinazoline formed per unit catalyst. Rate of formation of quinazoline per mole catalyst per unit time (15 h).

SHIMADZU UV-2450 spectrophotometer with a quartz cuvette

path length of 1 cm). To record FT-IR, a Varian 660 IR

Scheme 5. Control Experiment

(

spectrometer was used. Melting points were measured on Stuart

melting point apparatus and are uncorrected. H NMR spectra were

recorded on a Bruker Avance III HD 500 MHz with CDCl and

DMSO-d as solvents and tetramethylsilane and SiMe as internal

standards. Data is reported as follows: chemical shift in ppm (δ),

multiplicity (s = singlet, d = doublet, t = triplet, q = quintet, m =

multiplet, br = broad), coupling constants J (Hz). For the light

promoted reactions, 16 W white LEDs purchased from Philips

(Manufacturer: Signify Innovations India Limited, Model Number:

929001818814_2, λ > 410 nm, spectral distribution: 380−760 nm,

intensity: 1440 lm) were used. All the reactants and catalysts were

added to a 10 mL borosilicate round-bottom ﬂask and irradiated with

the mentioned light source (distance app. of 7−9 cm) without the use

of any ﬁlters. Blue LEDs (5 W) were purchased from Aluxcia

Scheme 6. Proposed Reaction Mechanism for the Synthesis of Quinazolines Using Supramolecular Nanoassemblies of TETPY

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

(

manufacturer: Aluxcia LED Co., Ltd., part no. ALC1020-Bx2-US-

W, λ > 455 nm) and used without any ﬁlters.

1225, 965, 842, 762, 724, 686, 624 (Figure S48, Supporting

Information).

Preparation of the Photocatalyst (Supramolecular Nano-

Gram-Scale Synthesis Procedure for the Synthesis of 3a

And 5a Using Supramolecular Nanoassemblies of TETPY as

the Photocatalytic System. For the gram-scale synthesis of 3a, a

mixture of o-phenylenediamine (1a) (13.8 mmol) and benzaldehyde

assemblies of TETPY). A 500 μL mixture of 4.0 mg of TETPY

dissolved in 800 μL of DMSO and 1200 μL of distilled water was used

as the photocatalyst for each photocatalytic reaction.

General Procedure for the Synthesis of 2-Benzimidazole/

Benzothiazole/Quinazolines Using the Isolated Form of

TETPY as the Photocatalytic System. For 2-benzimidazole and

benzothiazole synthesis, a mixture of o-phenylenediamine (1a)/o-

aminothiophenol (4) (0.5 mmol) and benzaldehyde (2a) (0.5 mmol)

in EtOH (2 mL) as the solvent in a 10 mL round-bottom ﬂask in the

presence of the isolated form of TETPY (1 mg) as the photocatalyst

was stirred at room temperature for 2 h/40 min, respectively, under

visible light irradiation (16 W white LED) and aerial conditions. For

(2a) (13.8 mmol) in EtOH/H O (1:1) (30 mL) in a 50 mL round-

bottom ﬂask in the presence of supramolecular nanoassemblies of

TETPY (0.1 mol %) as the photocatalyst was stirred at room

temperature for 2 h under visible light irradiation (16 W white LED)

and aerial conditions. For the gram-scale synthesis of 5a, a mixture of

o-aminothiophenol (4) (12 mmol) and benzaldehyde (2a) (12

mmol) in EtOH/H O (1:1) (30 mL) in a 50 mL round-bottom ﬂask

in the presence of supramolecular nanoassemblies of TETPY (0.1 mol

%) as the photocatalyst was stirred at room temperature for 40 min

under visible light irradiation (16 W white LED) and aerial

conditions. The reaction mixtures in reaction vessels were dipped in

a continuous ﬂow water bath to avoid photoheating eﬀects. The

progress of the reaction was monitored by TLC. After completion of

the reaction, the ﬁnal product (3a) was isolated after recrystallization

-quinazoline synthesis, a mixture of 2-aminobenzylamine (6) (0.5

mmol), benzaldehyde (2a) (0.5 mmol), and NEt (2 equiv) in EtOH

(

2 mL) as the solvent mixture in a 10 mL round-bottom ﬂask in the

presence of the isolated form of TETPY (1 mg) as the photocatalyst

was stirred at room temperature for 15 h under visible light irradiation

(

16 W white LED) and aerial conditions. The reaction mixture in a

(CHCl /MeOH) and the product 5a was isolated by column

reaction vessel was dipped in a continuous ﬂow water bath to avoid

photoheating eﬀects. The progress of the reaction was monitored by

TLC. After completion of the reaction, the ﬁnal product (3a) was

chromatography. Both the products were identiﬁed by HNMR

spectroscopy (Figures S10 and S32, Supporting Information).

General Procedure for the Synthesis of 2-Quinazolines

Using Supramolecular Nanoassemblies of TETPY as the

Photocatalytic System. A mixture of 2-aminobenzylamine (6)

isolated after recrystallization (CHCl /MeOH) and products 5a and

a were isolated by column chromatography. All the products were

(

0.5 mmol), substituted aldehyde (2a−d) (0.5 mmol), and NEt (2

identiﬁed by HNMR spectroscopy (Figures S10, S32, and S50 ,

equiv) in EtOH/H O (1:1) (2 mL) in a 10 mL round-bottom ﬂask in

Supporting Information).

General Procedure for the Synthesis of 2-Benzimidazoles/

Benzothiazoles Using Supramolecular Nanoassemblies of

TETPY as the Photocatalytic System. For 2-benzimidazole

derivative synthesis, a mixture of diamines (1a−d) (0.5 mmol) and

the presence of supramolecular nanoassemblies of TETPY (0.1 mol

%) as the photocatalyst was stirred at room temperature for 15 h

under visible light irradiation (16 W white LED) and aerial

conditions. The reaction mixture in a reaction vessel was dipped in

a continuous ﬂow water bath to avoid photoheating eﬀects. The

progress of the reaction was monitored by TLC. After completion of

the reaction, the organic part was extracted with EtOAc. The

combined organic layer was dried over anhydrous sodium sulfate and

concentrated under reduced pressure. The products were puriﬁed by

column chromatography using EtOAc/hexane as the eluent. All the

substituted aldehyde (2a−v) (0.5 mmol) in EtOH/H O (1:1) (2

mL) in a 10 mL round-bottom ﬂask in the presence of supramolecular

nanoassemblies of TETPY (0.1 mol %) as the photocatalyst was

stirred at room temperature for 2 h under visible light irradiation (16

W white LED) and aerial conditions. For 2-benzothiazole derivative

synthesis, a mixture of o-aminothiophenol (4) (0.5 mmol) and

substituted aldehyde (2a−m, 2w−x, 2o) (0.5 mmol) in EtOH/H O

products (7a−d) were identiﬁed by H NMR spectroscopy (Figures

(1:1) (2 mL) in a 10 mL round-bottom ﬂask in the presence of

S50 −S53 , Supporting Information).

supramolecular nanoassemblies of TETPY (0.1 mol %) as the

photocatalyst was stirred at room temperature for 40 min under

visible light irradiation (16 W white LED) and aerial conditions. The

reaction mixtures in reaction vessels were dipped in a continuous ﬂow

water bath to avoid photoheating eﬀects. The progress of the reaction

was monitored with TLC. After completion of the reaction, the ﬁnal

products of benzimidazoles derivatives (3a−v) were puriﬁed after

General Procedure for the Synthesis of 2-Phenyl-1,2,3,4-

tetrahydroquinazoline (8a). A mixture of 2-aminobenzylamine (6)

(0.5 mmol) and benzaldehyde (2a) (0.5 mmol) in EtOH/H O (1:1)

(2 mL) in a 10 mL round-bottom ﬂask was stirred for 2 h. The

progress of the reaction was monitored with TLC. After completion

of the reaction, the organic part was extracted with EtOAc. The

combined organic layer was dried over anhydrous sodium sulfate and

concentrated under reduced pressure. The products were puriﬁed by

column chromatography using EtOAc/hexane as the eluent. The

recrystallization (CHCl /MeOH). All the products (3a−v) were

identiﬁed by HNMR spectroscopy (Figures S10 −S31 , Supporting

Information). For benzothiazoles products, the combined organic

layer was dried over anhydrous sodium sulfate and concentrated

under reduced pressure. The products (5a−m, 5w−x, 5o) were

puriﬁed by column chromatography using EtOAc/hexane as the

product (8a) was identiﬁed by H NMR spectroscopy (Figure S54,

Supporting Information).

H NMR Characterization. 2-Phenyl-1H-benzimidazole (3a).

White solid (93 mg, 96% yield). m.p. 289−292 °C. H NMR (500

MHz, DMSO-d ): δ (ppm) 12.90 (br s, 1H), 8.17 (d, J = 5 Hz, 2H),

7.66 (d, J = 5 Hz, 1H), 7.57−7.48 (m, 4H), 7.24−7.17 (m, 2H).

eluent. All the products (5a −m , 5w −x , 5o ) were identiﬁed by H

NMR spectroscopy (Figures S32 −S46 and S49, Supporting

Information).

2-(4-Chlorophenyl)-1H-benzimidazole (3b). White solid (107

General Procedure for the Synthesis of 1,4-Diphenylben-

zothiazole (5y) Using Supramolecular Nanoassemblies of

mg, 94% yield). m.p. 291 °C. H NMR (500 MHz, DMSO-d ): δ

(ppm) 12.99 (br s, 1H), 8.17 (d, J = 5 Hz, 2H), 7.67−7.62 (m, 3H),

7.53 (d, J = 5 Hz, 1H), 7.21 (t, J = 5 Hz, 2H).

TETPY as the Photocatalytic system.

A mixture of o-

aminothiophenol (4) (1 mmol) and terephthalaldehyde (2y) (0.5

2-(4-Nitrophenyl)-1H-benzimidazole (3c). Oﬀ-white solid (113

mmol) in EtOH/H O (1:1) (2 mL) in a 10 mL round-bottom ﬂask in

mg, 95% yield). m.p. 328−329 °C. H NMR (500 MHz, DMSO-d ):

the presence of supramolecular nanoassemblies of TETPY (0.1 mol

δ (ppm) 13.31 (br s, 1H), 8.42 (s, 4H), 7.73 (d, J = 10 Hz, 1H), 7.59

(d, J = 10 Hz, 1H), 7.31−7.23 (m, 2H).

2-(4-Fluorophenyl)-1H-benzimidazole (3d). Pale yellow solid

%) as the photocatalyst was stirred at room temperature for 40 min

under visible light irradiation (16 W white LED) and aerial

conditions. The reaction mixture in a reaction vessel was dipped in

a continuous ﬂow water bath to avoid photoheating eﬀects. The

insoluble product was then ﬁltered and washed properly with ethanol.

(99 mg, 94% yield). m.p. 247−249 °C. H NMR (500 MHz, DMSO-

d ): δ (ppm) 12.92 (br s, 1H), 8.23−8.20 (m, 2H), 7.59 (d, J = 60

Hz, 2H), 7.40 (t, J = 10 Hz, 2H), 7.21 (s, 2H).

It was also characterized by HNMR spectroscopy (Figure S47 ,

4-(1H-Benzimidazol-2-yl)benzonitrile (3e). White solid (100

mg, 92% yield). m.p. 264−265 °C. H NMR (500 MHz, DMSO-d ): δ

−1

Supporting Information). FT-IR (ν/cm ): 1480, 1432, 1495, 1310,

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

Article

(

ppm) 8.34 (d, J = 10 Hz, 2H), 8.03 (d, J = 10 Hz, 2H), 7.65 (s, 2H),

.27 (s, 2H).

-(4-Triﬂuoromethylphenyl)-1H-benzimidazole (3f). White

d₆): δ (ppm) 13.26 (br s, 1H), 8.15 (d, J = 5 Hz, 2H), 8.07 (s, 1H),

7.90 (s, 1H), 7.59−7.53 (m, 3H).

Ferrocene Benzimidazole (3v). Yellow solid (129 mg, 86%

solid (92 mg, 92% yield). m.p. 265−266 °C. H NMR (500 MHz,

DMSO-d ): δ (ppm) 13.17 (br s, 1H), 8.38 (d, J = 5 Hz, 2H), 7.93

yield). m.p. 235−236 °C (decomposition). HNMR (500 MHz,

DMSO-d ): δ (ppm) 12.34 (br s, 1H), 7.49 (d, J = 50 Hz, 2H), 7.13

(

d, J = 10 Hz, 2H), 7.71 (d, J = 10 Hz, 1H), 7.57 (d, J = 10 Hz, 1H),

.28−7.21 (m, 2H).

-(4-Bromophenyl)-1H-benzimidazole (3g). White solid (128

(s, 2H), 5.04 (s, 2H), 4.47 (s, 2H), 4.10 (s, 5H).

2-Phenylbenzothiazole (5a). Pale yellow solid (102 mg, 97%

yield). m.p. 112 °C. H NMR (500 MHz, CDCl ): δ (ppm) 8.11−8.07

mg, 95% yield). m.p. 283−284 °C. H NMR (500 MHz, DMSO-d ):

δ (ppm) 13.03 (br s, 1H), 8.11 (d, J = 10 Hz, 2H), 7.76 (d, J = 5 Hz,

(m, 3H), 7.91 (d, J = 5 Hz, 1H), 7.51−7.49 (m, 4H), 7.39 (t, J = 10

Hz, 1H).

H), 7.54 (m, 2H), 7.18 (m, 2H).

2-(4-Chlorophenyl) Benzothiazole (5b). White solid (117 mg,

-(2-Chlorophenyl)-1H-benzimidazole (3h). Brown solid (102

96% yield). m.p. 115−116 °C. H NMR (500 MHz, CDCl ): δ

mg, 90% yield). m.p. 232−234 °C. H NMR (500 MHz, DMSO-d ):

δ (ppm) 12.73 (br s, 1H), 7.90 (d, J = 10 Hz, 1H), 7.67 (dd, J = 25

Hz, 2H), 7.57−7.51 (m, 3H), 7.27−7.21 (m, 2H).

(ppm) 8.07 (d, J = 10 Hz, 1H), 8.03 (d, J = 10 Hz, 2H), 7.91 (d, J =

10 Hz, 1H), 7.52−7.47 (m, 3H), 7.40 (t, J = 10 Hz, 1H).

2-(4-Nitrophenyl) Benzothiazole (5c). Yellow solid (120 mg,

-(3-Nitrophenyl)-1H-benzimidazole (3i). White solid (109 mg,

94% yield). m.p. 233 °C. H NMR (500 MHz, CDCl ): δ (ppm) 8.36

2% yield). m.p. 203 °C. H NMR (500 MHz, DMSO-d ): δ (ppm)

3.31 (br s, 1H), 9.02 (s, 1H), 8.61 (d, J = 5 Hz, 1H), 8.33 (d, J = 5

(d, J = 10 Hz, 2H), 8.27 (d, J = 5 Hz, 2H), 8.13 (d, J = 5 Hz, 1H),

7.96 (d, J = 5 Hz, 1H), 7.56 (t, J = 10 Hz, 1H), 7.46 (t, J = 5 Hz, 1H).

Hz, 1H), 7.86 (t, J = 10 Hz, 1H), 7.65 (d, J = 55 Hz, 2H), 7.26 (s,

H).

-(4-Methoxyphenyl)-1H-benzimidazole (3j). White solid (99

2-(4-Fluorophenyl) Benzothiazole (5d). White solid (106 mg,

93% yield). m.p. 102 °C. H NMR (500 MHz, CDCl ): δ (ppm)

8.11−8.06 (m, 3H), 7.91 (d, J = 10 Hz, 1H), 7.50 (t, J = 10 Hz, 1H),

mg, 89% yield). m.p. 220 °C. H NMR (500 MHz, DMSO-d ): δ

(

7.39 (t, J = 5 Hz, 1H), 7.21−7.17 (m, 2H).

ppm) 8.11 (d, J = 10 Hz, 2H), 7.55 (s, 2H), 7.18−7.16 (m, 2H),

.11 (d, J = 10 Hz, 2H), 3.84 (s, 3H).

-(4-Ethylphenyl)-1H-benzimidazole (3k). White solid (102 mg,

4-(Benzothiazole-2-yl) Benzonitrile (5e). White solid (110 mg,

94% yield). m.p. 169−170 °C. H NMR (500 MHz, CDCl ): δ (ppm)

8.19 (d, J = 5 Hz, 2H), 8.11 (d, J = 10 Hz, 1H), 7.94 (d, J = 10 Hz,

1H), 7.78 (d, J = 10 Hz, 2H), 7.54 (t, J = 10 Hz, 1H), 7.44 (t, J = 5

Hz, 1H).

(

2% yield). m.p. 143−145 °C. H NMR (500 MHz, DMSO-d ): δ

ppm) 12.84 (br s, 1H), 8.08 (d, J = 10 Hz, 2H), 7.63 (d, J = 5 Hz,

H), 7.51 (d, J = 10 Hz, 1H), 7.39 (d, J = 10 Hz, 2H), 7.22−7.16 (m,

2-(4-Triﬂuoromethylphenyl) Benzothiazole (5f). White solid

H), 2.67 (q, J = 10 Hz, 2H), 1.22 (t, J = 10 Hz, 3H).

(102 mg, 95% yield). m.p. 162−164 °C. H NMR (500 MHz,

-(4-Isopropylphenyl)-1H-benzimidazole (3l). White solid (110

CDCl ): δ (ppm) 8.21 (d, J = 10 Hz, 2H), 8.11 (d, J = 10 Hz, 1H),

mg, 94% yield). m.p. 249−250 °C. H NMR (500 MHz, DMSO-d ):

δ (ppm) 12.85 (br s, 1H), 8.09 (d, J = 10 Hz, 2H), 7.64 (d, J = 10 Hz,

7.94 (d, J = 10 Hz, 1H), 7.76 (d, J = 10 Hz, 2H), 7.53 (t, J = 10 Hz,

1H), 7.43 (t, J = 5 Hz, 1H).

H), 7.51 (d, J = 10 Hz, 1H), 7.42 (d, J = 10 Hz, 2H), 7.22−7.14 (m,

2-(4-Bromophenyl) Benzothiazole (5g). White solid (138 mg,

H), 2.99−2.93 (m, 1H), 1.24 (d, J = 5 Hz, 6H).

96% yield). m.p. 132 °C. H NMR (500 MHz, CDCl ): δ (ppm) 8.07

-(Naphthalen-2-yl)-1H-benzimidazole (3m). White solid (114

(d, J = 10 Hz, 1H), 7.96 (d, J = 5 Hz, 2H), 7.91 (d, J = 10 Hz, 1H),

7.63 (d, J = 10 Hz, 2H), 7.50 (t, J = 5 Hz, 1H), 7.40 (t, J = 5 Hz, 1H).

mg, 94% yield). m.p. 220−221 °C. H NMR (500 MHz, DMSO-d ):

δ (ppm) 8.84 (s, 1H), 8.27−8.23 (m, 2H), 8.14−8.07 (m, 2H), 7.87−

2-(2-Chlorophenyl) Benzothiazole (5h). Pale yellow solid (112

.85 (m, 2H), 7.76−7.71 (m, 2H), 7.57−7.55 (m, 2H).

mg, 92% yield). m.p. 85 °C. H NMR (500 MHz, CDCl ): δ (ppm)

-(1H-Benzimidazol-2-yl) Phenol (3n). White solid (92 mg, 88%

8.23−8.20 (m, 1H), 8.14 (d, J = 10 Hz, 1H), 7.96 (d, J = 10 Hz, 1H),

yield). m.p. 254 °C. H NMR (500 MHz, DMSO-d ): δ (ppm) 10.08

(

7.56−7.52 (m, 2H), 7.46−7.40 (m, 3H).

s, 1H), 8.00 (d, J = 10 Hz, 2H), 7.57−7.55 (m, 2H), 7.21−7.20 (m,

H), 6.93 (d, J = 10 Hz, 2H).

2-(3-Nitrophenyl) Benzothiazole (5i). Yellow solid (119 mg,

94% yield). m.p. 183 °C. H NMR (500 MHz, CDCl ): δ (ppm) 8.94

H-Benzimidazole (3o). White solid (47 mg, 80% yield). m.p.

(s, 1H), 8.41 (d, J = 10 Hz, 1H), 8.34 (d, J = 10 Hz, 1H), 8.12 (d, J =

10 Hz, 1H), 7.94 (d, J = 10 Hz, 1H), 7.69 (d, J = 10 Hz, 1H), 7.54 (t,

J = 5 Hz, 1H), 7.45 (t, J = 5 Hz, 1H).

70−172 °C. H NMR (500 MHz, DMSO-d ): δ (ppm) 12.41 (br s,

H), 8.20 (s, 1H), 7.58 (s, 2H), 7.18 (s, 2H).

,5,6-Trimethyl-1H-benzimidazole (3p). Yellow solid (62 mg,

8% yield). m.p. 229−231 °C. H NMR (500 MHz, DMSO-d ): δ

ppm) 7.19 (s, 2H), 2.42 (s, 3H), 2.26 (s, 6H).

-(Furan-2-yl)-1H-benzimidazole (3q). Yellow solid (78 mg,

2-(4-Methoxyphenyl) Benzothiazole (5j). White solid (108 mg,

(

90% yield). m.p. 123−125 °C. H NMR (500 MHz, CDCl ): δ (ppm)

8.05−8.02 (m, 3H), 7.88 (d, J = 10 Hz, 1H), 7.47 (t, J = 10 Hz, 1H),

7.35 (t, J = 5 Hz, 1H), 7.01 (d, J = 10 Hz, 2H), 3.89 (s, 3H).

(

5% yield). m.p. 284−286 °C. H NMR (500 MHz, DMSO-d ): δ

2-(4-Ethylphenyl) Benzothiazole (5k). Pale yellow solid (111

ppm) 12.92 (br s, 1H), 7.94 (s, 1H), 7.62 (d, J = 10 Hz, 1H), 7.49

d, J = 10 Hz, 1H), 7.23−7.17 (m, 3H), 6.73−6.72 (m, 1H).

mg, 93% yield). m.p. 63 °C. H NMR (500 MHz, CDCl ): δ (ppm)

8.06 (d, J = 5 Hz, 1H), 8.01 (d, J = 5 Hz, 2H), 7.89 (d, J = 5 Hz, 1H),

7.48 (t, J = 5 Hz, 1H), 7.37 (t, J = 10 Hz, 1H), 7.33 (d, J = 10 Hz,

2H), 2.72 (q, J = 10 Hz, 2H), 1.28 (t, J = 5 Hz, 3H).

-(Thiophen-2-yl)-1H-benzimidazole (3r). Yellow solid (85 mg,

(

5% yield). m.p. 330−331 °C. H NMR (500 MHz, DMSO-d ): δ

ppm) 12.94 (br s, 1H), 7.82 (d, J = 5 Hz, 1H), 7.72 (d, J = 5 Hz,

2-(4-Isopropylphenyl) Benzothiazole (5l). White solid (118 mg,

H), 7.60 (d, J = 5 Hz, 1H), 7.49 (d, J = 5 Hz, 1H), 7.24−7.16 (m,

94% yield). m.p. 78−80 °C. H NMR (500 MHz, CDCl ): δ (ppm)

H).

8.06 (d, J = 5 Hz, 1H), 8.02 (d, J = 10 Hz, 2H), 7.90 (d, J = 10 Hz,

1H), 7.48 (t, J = 5 Hz, 1H), 7.39−7.35 (m, 3H), 2.97 (septet, J = 10

Hz, 1H), 1.30 (d, J = 10 Hz, 6H).

-(Thiophen-3-yl)-1H-benzimidazole (3s). Oﬀ-white solid (89

mg, 86% yield). m.p. 347 °C (decomposition). H NMR (500 MHz,

DMSO-d ): δ (ppm) 12.80 (br s, 1H), 8.23 (s, 1H), 7.77 (d, J = 5 Hz,

2-(Naphthalen-2-yl) Benzothiazole (5m). White solid (123 mg,

H), 7.73−7.72 (m, 1H), 7.62 (d, J = 10 Hz, 1H), 7.50 (d, J = 10 Hz,

95% yield). m.p. 129 °C. H NMR (500 MHz, CDCl ): δ (ppm) 8.58

H), 7.22−7.15 (m, 2H).

(s, 1H), 8.22 (d, J = 10 Hz, 1H), 8.12 (d, J = 10 Hz, 1H), 7.99−7.93

(m, 3H), 7.90−7.88 (m, 1H), 7.58−7.50 (m, 3H), 7.41 (t, J = 10 Hz,

1H).

-(4-Chlorophenyl)-5-methyl-1H-benzimidazole (3t). White

solid (108 mg, 90% yield). m.p. 223−224 °C. H NMR (500 MHz,

DMSO-d ): δ (ppm) 12.83 (d, J = 25 Hz, 1H), 8.16 (d, J = 10 Hz,

4-(Benzothiazol-2-yl)-N,N-dimethylaniline (5w). Yellow solid

H), 7.61 (d, J = 5 Hz, 2H), 7.54−7.31 (m, 2H), 7.06−7.01 (m, 1H),

(119 mg, 95% yield). m.p. 128−130 °C. H NMR (500 MHz,

.42 (d, J = 10 Hz, 3H).

CDCl ): δ (ppm) 7.99−7.95 (m, 3H), 7.84 (d, J = 10 Hz, 1H), 7.43

,6-Dibromo-2-phenyl-1H-benzimidazole (3u). White solid

(t, J = 10 Hz, 1H), 7.30 (t, J = 10 Hz, 1H), 6.75 (d, J = 10 Hz, 2H),

(

159 mg, 91% yield). m.p. 177 °C. H NMR (500 MHz, DMSO-

3.06 (s, 6H).

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

(1) Tateyama, K.; Wada, K.; Miura, H.; Hosokawa, S.; Abe, R.;

Article

-(4-Methylphenyl) Benzothiazole (5x). White solid (103 mg,

Author Contributions

All the experiments were performed and compiled by S.D. V.B.

and M.K. supervised the work and led the project.

2% yield). m.p. 85−86 °C. H NMR (500 MHz, CDCl ): δ (ppm)

.06 (d, J = 10 Hz, 1H), 7.99 (d, J = 10 Hz, 2H), 7.89 (d, J = 5 Hz,

H), 7.48 (t, J = 10 Hz, 1H), 7.37 (t, J = 10 Hz, 1H), 7.30 (d, J = 10

Hz, 2H), 2.43 (s, 3H).

,4-Diphenylbenzothiazole (5y). Oﬀ-white solid (163 mg, 95%

yield). m.p. 261−263 °C. H NMR (500 MHz, CDCl ): δ (ppm) 8.24

s, 4H), 8.12 (d, J = 10 Hz, 2H), 7.94 (d, J = 5 Hz), 7.53 (t, J = 10

Notes

The authors declare no competing ﬁnancial interest.

ACKNOWLEDGMENTS

V.B. is thankful to SERB, New Delhi (ref. no. CRG/2018/

01274), CSIR New Delhi (No. 02(0358/19/EMR-II) and

(

■

Hz, 2H), 7.42 (t, J = 5 Hz, 2H).

Benzothiazole (5o). Yellow oil (59 mg, 88% yield). b.p. 227−229

C. H NMR (500 MHz, CDCl ): δ (ppm) 8.96 (s, 1H), 8.12 (d, J =

0 Hz, 1H), 7.92 (d, J = 5 Hz, 1H), 7.49 (t, J = 10 Hz, 1H), 7.40 (d, J

5 Hz, 1H).

-Phenylquinazoline (7a). White solid (95 mg, 93% yield). m.p.

RUSA 2.0 for the ﬁnancial support. S.D. is thankful to DST-

INSPIRE (New Delhi) for Senior Research Fellowship (SRF).

ABBREVIATIONS

01−103 °C. HNMR (500 MHz, CDCl ): δ (ppm) 9.48 (s, 1H),

■

.61 (d, J = 5 Hz, 2H), 8.10 (d, J = 10 Hz, 1H), 7.94−7.90 (m, 2H),

.62 (t, J = 10 Hz, 1H), 7.56−7.50 (m, 3H).

AIEE, aggregation-induced emission enhancement; ICT,

intramolecular charge transfer; PC, photocatalyst; TON,

turnover number; TOF, turnover frequency

-(4-Chlorophenyl) Quinazoline (7b). White solid (108 mg, 90%

yield). m.p. 136−138 °C. H NMR (500 MHz, CDCl ): δ (ppm)

.46 (s, 1H), 8.57 (d, J = 10 Hz, 2H), 8.08 (d, J = 10 Hz, 1H), 7.95−

.91 (m, 2H), 7.63 (t, J = 5 Hz, 1H), 7.50 (d, J = 5 Hz, 2H).

-(4-Nitrophenyl) Quinazoline (7c). White solid (111 mg, 89%

yield). m.p. 222−234 °C. H NMR (500 MHz, CDCl ): δ (ppm)

.52 (s, 1H), 8.83 (d, J = 10 Hz, 2H), 8.38 (d, J = 10 Hz, 2H), 8.14

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