Greener Protocol for the Synthesis of NIR Fluorescent Indolenine

Subscriber access provided by UNIV OF NEW ENGLAND ARMIDALE

Article

Greener protocol for the synthesis of NIR fluorescent indolenine based symmetrical squaraine colorants Sushil Sitaram Khopkar, Saurabh Satish Deshpande, and Ganapati S. Shankarling ACS Sustainable Chem. Eng., Just Accepted Manuscript • DOI: 10.1021/acssuschemeng.8b02095 • Publication Date (Web): 11 Jul 2018 Downloaded from http://pubs.acs.org on July 15, 2018

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

ACS Sustainable Chemistry & Engineering

Greener protocol for the synthesis of NIR fluorescent

indolenine

based

symmetrical

squaraine colorants Sushil Khopkara , Saurabh Deshpandea, Ganapati Shankarling*a a

Department of Dyestuff Technology, Institute of Chemical Technology, N. P. Marg, Matunga,

Mumbai - 400019, Maharashtra, India *Corresponding author. Tel.: 91-22-33612708; fax: +91-22-33611020 E-mail: [email protected]

ABSTRACT

An environmentally benign synthesis of NIR fluorescent indolenine based symmetrical squaraines is accomplished by using choline chloride: urea as a bio-renewable deep eutectic solvent (DES). This ammonium DES is biodegradable and serves a dual role, catalyst as well as the reaction medium. Furthermore, DES has been recycled upto four consecutive cycles without significant loss in its activity. The developed method has many advantages compared to those reported in literature including being environmentally more benign, operational simplicity, low reaction temperature, ease of product isolation, low environmental factor (E-factor) and higher yield for the synthesis of symmetrical squaraine colorants in short reaction time. In addition, the present method could be implemented on a multigram scale. Thus it provides a good alternative route for the industrial synthesis of squaraine colorants.

ACS Paragon Plus Environment

1

ACS Sustainable Chemistry & Engineering 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 2 of 28

KEYWORDS

Squaraines, fluorescence, deep eutectic solvent, green chemistry, recyclability

INTRODUCTION Squaraines are 1, 3-disubstituted squaric acids existing in a zwitter-ionic form which constitutes of donor-acceptor–donor (D–A–D) structure due to the strong electron withdrawing central squaryl moiety flanked between aromatic or heterocyclic donor rings on either side. Their planar rigid structure, a strong narrow absorption in the Visible / NIR region, high molar extinction coefficient, intense fluorescence spectra in the red and near-infrared region, good solubility in low polarity solvents, remarkable chemical stability, high redox reversibility, inherent photostability and good photoconductivity are noteworthy properties of these dyes.1-4 These unique electronic structure and optical properties renders them most suitable for a wide range of technological applications such as metal ion sensors5, sensitizers in DSSC6,photodynamic therapy7, electrophotography8, long wavelength fluorescent biomedical labels and probes9, nonlinear optics10,optical data storage11,TPA applications12, biomedical imaging13,xerographic organic photoreceptors14, photoconductive material in photocopies15 and light emitting field effect transistors16. The synthesis of anhydrobases derived symmetrical squaraines involves the dicondensation between two equivalents of nucleophilic heterocyclic or aromatic anhydrobase consisting of an active methyl group and one equivalent of squaric acid with removal of water using the DeanStarc trap. Conventionally, the reaction is carried out in a mixture of high boiling alcohol and aromatic hydrocarbons such as n-butanol: toluene17, n-butanol: benzene18, iso-propanolbenzene19 and n-butanol-pyridine20 with catalytic amount of quinoline or pyridine acting as a


2

Page 3 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


base to convert quaternary salts of anhydrobases into enamines which subsequently condense with squaric acid to yield symmetrical squaraines at high temperatures. However, use of hazardous solvents, high reaction temperatures, tedious work up procedures, difficulties in product isolation from high boiling alcohols and eventually low yields are some of the major drawbacks associated with these conventional protocols which could ultimately harm the environment. Subsequently, it has become very essential to find out alternative ways for the synthesis of the important and in-demand squaraines. Recently, Barbero et al developed a protocol for the synthesis of squaraines with high yield in reduced reaction time by use of microwave method.21 As stated in the third principle of green and sustainable chemistry, solvents should have to meet different criteria such as biodegradability, renewability, inflammability and non-toxicity. In last two decades, deep eutectic solvents (DESs), a mixture of hydrogen bond donors and hydrogen bond acceptors, have gained tremendous importance in organic synthesis as it reduces the use of volatile, flammable, explosive and toxic traditional organic solvents as well as increases the rate of reactions. Easy availability of the constituents, bio-degradability, nonflammability, non –toxicity are few important advantages associated with these solvent system2224

. ChCl: urea DES is formed by complexation of choline chloride (ChCl) with a hydrogen bond

donor urea. Choline chloride and urea are both naturally occurring biocompatible compounds that are not hazardous if they are released back into nature. Recently, these type of deep eutectic solvent systems have been fruitfully explored for the synthesis of coumarin dyes25, spirooxindole26, 4H-Chromenes27, naphthyridines28, tricyanovinylated aromatics29, oxazoles30 and βfunctionalized ketonic derivatives31.


3


Page 4 of 28

Thus considering the drawbacks associated with the conventional protocols for squaraine synthesis and knowing the importance of the deep eutectic solvent systems and their environmental benign impact, herein we demonstrate the synthesis of NIR fluorescent indolenine based symmetrical squaraine colorants in ChCl: urea deep eutectic solvent for the first time. Mild reaction conditions, good to excellent product yields in short reaction times and recyclability of the solvent system are some of the important advantages offered by the developed protocol. To the best of our knowledge, no green syntheses of symmetrical squaraines using DES have been reported. EXPERIMENTAL SECTION Preparation of deep eutectic solvent (choline chloride: urea, 1:2) The deep eutectic solvent was synthesized according to the reported procedure.32 Choline chloride (100 g, 70 mmol) and urea (86 g, 140 mmol) were placed in a round bottom flask and heated to 80 oC, until a liquid began to form. After 15 to 20 minutes, a homogeneous colorless liquid (186 g, 100%) formed which was used directly for the reactions without further purification. General procedure for the synthesis of indolenines and its quaternized salts (1a-o) For the synthesis of indolenine derivatives, we exploited the Fischer indole synthesis by condensation of benzohydrazine substitutes with methyl iso-propyl ketone in glacial acetic acid 33

and for nitro indolenine derivatives we have utilized glacial acetic acid – sulphuric acid

mixture.34 The quaternization of indolenines has traditionally been carried out with an excess of alkylating agent in acetonitrile over several hours or days.33 General procedure for the synthesis of symmetrical squaraine derivatives (3a-o)


4

Page 5 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


2 mmol of indolenine or indolenium iodide and 1 mmol of squaric acid were added to 5 ml of DES in a 50 ml round bottom flask. The reaction mixture was stirred and heated at 80 oC for the appropriate time as shown in Table 2. The reaction progress was monitored by thin layer chromatography (TLC). After completion of the reaction, cold water was added to the reaction mixture while stirring. The DES being soluble in water comes in the aqueous layer. The resulting residue was then separated by filtration and washed with diethyl ether to afford the pure product. RESULTS AND DISCUSSION Traditionally, a mixture of two equivalents of anhydrobase and one equivalent of squaric acid in a high boiling alcohol: aromatic hydrocarbon azeotropic solvents comprising a small amount of base such as pyridine or quinoline as a catalyst gives anhydrobases derived symmetrical squaraines. Here we have demonstrated an environmentally friendly synthesis of anhydrobases derived symmetrical squaraines using choline chloride: urea (1:2) based deep eutectic solvent which has resulted in eliminating the need of azeotropic solvents, high reaction temperatures and increased reaction times. The conversion obtained by this method is significantly better in comparison with traditional synthetic methods. Our reported method scores over the conventional method due to the fact that during work-up organic bases such as pyridine, quinoline and high boiling alcohols do not need to be separately removed. Additionally, our method involves simple experimental set-up as it does not require the use of a Dean-starc trap to remove water from the reaction mixture. To investigate the feasibility of our protocol in the choline chloride: urea deep eutectic solvent, the condensation reaction of 1, 2, 3, 3-tetramethyl-3H-indol-1-ium iodide 1b (2 mmol) and squaric acid 2 (1 mmol) for the synthesis of compound 3b was chosen as a model reaction.


5


Page 6 of 28

Initially, this model reaction was performed in different traditional azeotropic solvents (n-BuOH: toluene, n-BuOH: benzene, iso-propanol: benzene, n-BuOH: pyridine), deep eutectic solvents (ChCl: Urea, ChCl:malonic acid, Choline hydroxide ), Lewis acid metal chlorides ( SnCl2, ZnCl2, LaCl3) as well as a combination of traditional and deep eutectic solvents (ChCl: Urea – Toluene, ChCl: Urea - n-BuOH, ChCl: Urea - n-BuOH: toluene) (Table 1, entries 1-15). The best result was obtained in choline chloride: urea (1:2) solvent for the synthesis of 3b (Table 1, entry 5). This is possible because of two reasons (i) the Lewis basic sites of urea can activate CH bond of indolenine so that acidic proton is abstracted by DES to form a carbanion (ii) choline chloride might help to stabilize the squaric acid carbonyl groups by hydrogen bonding. In the seventh entry, the reaction was performed in choline hydroxide and although yield was less, it indicated that choline hydroxide may help in the formation of carbanion. Based on these results, further reactions were optimized using ChCl: Urea (1:2) solvent which serves a dual role, as both catalyst and solvent. Next, ChCl: urea DES loading experiments were performed to study its influence on the product yield (Table 1, entries 16-20). For this purpose, the model reaction was carried out with varying DES loading from 1.0 ml to 6.0 ml. It is observed that there is a dramatic increase in the product yield from 15 % to 70 % as we increase the solvent loading from 1.0 ml to 5.0 ml (Table 1, entries 16-19). The improvement in the yield can be attributed to the ready convergence and increased interactions between reacting molecules. Further increase in DES loading (6.0 ml) did not improve the yield of product (Table 1, entry 20). Thus the model reaction was efficient in 5.0 ml of DES. Further, the yield of product was optimized by temperature of the reaction. For this purpose, the model reaction was carried out for a period of one hour with varying temperatures from RT to 100 oC (Table 1, entries 21-25). At room temperature only starting materials were recovered (Table 1, entry 21). Further, the reaction was


6

Page 7 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


carried at high temperatures i.e 40 oC, 60 oC, 80 oC, 100 oC and the yield of product 3b was improved to 70 % when the reaction was run at 80 °C (Table 1, entry 24). Any change in this temperature resulted in lowering of yield. Subsequently, the effect of reaction time on the yield of product was also investigated and 60 minutes was found to be sufficient time for synthesis of 3b with high yield (Table 1, entry 28). From these investigations, 1, 2, 3, 3 -tetramethyl-3Hindol-1-ium iodide 1b (2 mmol), squaric acid 2 (1 mmol), ChCl: urea DES (5.0 ml), 80 °C temperature and 60 minutes time were found to be the best reaction parameters for the synthesis of compound 3b. Table 1: Optimization study for DES (ChCl: urea, 1:2) mediated synthesis of symmetrical squarainesa

Entry

solvent

time

temp.

yield

(min.)

(oC)

(%)b

Effect of the catalyst as well as solvent 1

n-BuOH: toluene (1:1 v/v)

60

Reflux

30

2

n-BuOH: benzene (1:1 v/v)

60

Reflux

30

3

iso-propanol: benzene (1:1 v/v)

60

Reflux

28

4

n-BuOH: pyridine (1:1 v/v)

60

Reflux

38

5

ChCl: urea (1:2)

60

80

70


7


Page 8 of 28

6

ChCl:malonic acid (1:2)

60

80

NR

7

Choline hydroxide

60

80

58

8

Choline chloride

60

80

32c

9

Urea

60

80

15c

10

SnCl2

60

80

NRd

11

ZnCl2

60

80

NRd

12

LaCl3

60

80

NRd

13

ChCl: urea – toluene

60

80

42e

14

ChCl: urea - n-BuOH

60

80

46e

15

ChCl: urea - n-BuOH: toluene

60

80

45e

Effect of catalyst as well as solvent loading 16

ChCl: urea (1.0 ml)

60

80

15

17

ChCl: urea (3.0 ml)

60

80

42

18

ChCl: urea (4.0 ml)

60

80

58

19

ChCl: urea (5.0 ml)

60

80

70

20

ChCl: urea (6.0 ml)

60

80

70

Effect of temperature 21

ChCl: urea (5.0 ml)

60

RT

NR

22

ChCl: urea (5.0 ml)

60

40

22

23

ChCl: urea (5.0 ml)

60

60

56

24

ChCl: urea (5.0 ml)

60

80

70

25

ChCl: urea (5.0 ml)

60

100

70

Effect of time


8

Page 9 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


26

ChCl: urea (5.0 ml)

20

80

30

27

ChCl: urea (5.0 ml)

40

80

55

28

ChCl: urea (5.0 ml)

60

80

70

29

ChCl: urea (5.0 ml)

80

80

70

a

Reaction conditions: 1, 2, 3, 3-tetramethyl-3H-indol-1-ium iodide 1b (2 mmol), squaric acid 2 (1 mmol), solvent (5.0 ml), b isolated yield ,c 0.2 g of catalyst, d 20 mg of catalyst, e ChCl:urea as a catalyst , NR= no reaction Symmetrical squaraines based on the unquaternized indolenines are usually applied for the chemosensor applications as –NH of indolenine ring is capable of forming hydrogen bond with anion35 as well as it helps in cation complexation.36 In addition, many symmetrical squaraines are modified at N-alkyl group and C-5 position indolenine for fluorescence properties

37

and

potential applications such as electroactive devices3, photodynamic therapy38, dye sensitized solar cells6 etc. Therefore, after the optimized reaction conditions in hand, we explored the synthetic scope of this developed protocol for synthesis of the symmetrical squaraines having electron donating and withdrawing groups at C-5 position of indolenine with both quaternized and unquaternized forms. The results summarized in Table 2 clearly demonstrate that DES is an excellent catalyst as well as reaction media for the synthesis of symmetrical squaraines in terms of yields and time. As shown in Table 2, the C-5 unsubstituted and unquaternized indolenine 1a reacted with squaric acid 2, gave the product 3a of 64 % yield (Table 2, entry 2).In general, the quaternized indolenines afforded high yield of squaraines as compared to its unquaternized form. For example, quaternization of the indolenine nitrogen by methyl and ethyl group (1b and 1c) resulted in improvement of yield from 64 % to 75 % (Table 2, entries 4, 7) .However, extension of alkyl chain from ethyl to hexyl resulted in decrease of the yield. Consequently, indolenines possessing N-butyl and N-Hexyl chains (1d and 1e) gave the products 3d and 3e in 62 % and 55 % respectively (Table 2, entries 9, 11).In the case of indolenines bearing weak electron


9


Page 10 of 28

accepting group such as –Br group at C-5 position (1f-h), the yields were slightly higher as compared to their C-5 unsubstituted indolenines (Table 2, entries 13, 15, 17).On the other hand, indolenines with [4, 5]-benzo (1i-l) and strong electron accepting –NO2 substituent (1m-o) at C-5 position produced excellent yield of products (3i-o) (Table 2, entries 19,21,23,25,27,29,31). Next, we have also observed the C-5 substituent effect of indolenines on the time of reaction that is, indolenines possessing strong electron accepting groups reacted slowly as compared to its unsubstituted indolenines. For example, 5-nitroindolenine 1m gave 91 % yield of squaraine 3m in 118 minutes while unsubstituted indolenine 1a required 55 minutes for reaction completion to afford squaraine 3a (Table 2, entries 2, 27).Additionally, we investigated the reaction of 1b with diethyl squarate which gave the reduced yield (58 %) of product 3b as compared to its reaction with a squaric acid (Table 2, entry 5).This is due to the increase in yield of 3b semisquaraine ( 30 %) in the reaction mixture. Table 2: Synthesis of various indolenine based symmetrical squaraines a O

X

Method A Method B

O

+ N+ R I-

1a-o

HO

OH

X

Method C

ON+ R O

R N X

3a-o

2

Method A: n-BuOH: Tol (1:1 V/V) or n-BuOH: benzene (4:1 V/V), pyridine or quinoline, Dean -starc trap, 120 oC Method B: n-BuOH; Tol (1:1 V/V), pyridine or quinoline, Dean -starc trap, microwave, 160 o

C. Method C: ChCl: urea DES, 80 oC


10

Page 11 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Entry

X

R

product

method

time

yield

(min.)

(%)b

1

H

H

3a

A

180

5539

2

H

H

3a

C

55

64

3

H

CH3

3b

A

180

6139

4

H

CH3

3b

C

60

70

5

H

CH3

3b

Cc

60

58

6

H

C2H5

3c

A

180

6639

7

H

C2H5

3c

C

68

75

8

H

n-C4H9

3d

A

1440

3937

9

H

n-C4H9

3d

C

90

62

10

H

n-C6H13

3e

A

2160

4220

11

H

n-C6H13

3e

C

105

55

12

Br

H

3f

B

30

6640

13

Br

H

3f

C

84

71

14

Br

CH3

3g

A

960

3741

15

Br

CH3

3g

C

90

78

16

Br

C2H5

3h

B

30

8240

17

Br

C2H5

3h

C

95

80

18

4,5[benzo]

H

3i

A

360

5736

19

4,5[benzo]

H

3i

C

115

88

20

4,5[benzo]

CH3

3j

A

-

8042

21

4,5[benzo]

CH3

3j

C

120

93


11


Page 12 of 28

22

4,5[benzo]

C2H5

3k

A

2160

5817

23

4,5[benzo]

C2H5

3k

C

135

96

24

4,5[benzo]

(CH2)2COOH

3l

A

-

2043

25

4,5[benzo]

(CH2)2COOH

3l

C

180

52

26

NO2

H

3m

A

-

8044

27

NO2

H

3m

C

118

91

28

NO2

CH3

3n

A

180

9244

29

NO2

CH3

3n

C

125

95

30

NO2

C2H5

3o

A

-

-

31

NO2

C2H5

3o

C

140

97

a

Reaction conditions: 1a-o (2.0 mmol), 2 (1.0 mmol), ChCl:urea DES (5.0 ml) at 80 oC ,b isolated yield. c

reaction carried out using diethyl squarate

For industrial applicability of the present protocol, it is essential to recover and reuse the catalyst i.e. in this case a DES. For this purpose, the model reaction involving condensation of 1, 2, 3, 3-tetramethyl-3H-indol-1-ium iodide 1b and squaric acid 2 for the synthesis of compound 3b in DES under optimized reaction conditions was studied. After completion of the reaction, cold water was added to the reaction mixture and the residue (product) was separated by filtration. The DES was then recovered easily from the filtrate by evaporating water under vacuum. The recycled DES was used for next reactions with minimal loss of its activity upto four consecutive cycles (from 70 % on the first use to 63 % on the fourth) (Figure 1A). The structure of fresh and recycled DES was confirmed by using FT-IR and 1H NMR spectroscopy. In FT-IR spectra of fresh DES, the absorption peaks at 3324 cm-1 and 3193 cm-1 are


12

Page 13 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


characteristics of N-H and O-H stretching respectively. The band at 1630 cm-1 result from C=O stretching of urea. Also, a peak appears at around 1438 cm-1 and 1162 cm-1 are characteristics of C-H (-CH3) and C-N stretching frequency vibrations (Figure 1B). H1 NMR spectra of the DES showed characteristics signals at 3.14, 3.45, 3.99 and 4.63 ppm for –CH3, -CH2, -CH2 and –OH protons of choline chloride while signal at 5.76 ppm corresponds to –NH2 protons of urea (See Supporting Information, page S37). There is no spectral change observed in FT-IR and 1H NMR spectra of DES recycled after four runs indicating high purity and stability of recycled DES.

Figure 1: (A) Recyclability of deep eutectic solvent (ChCl: urea) for the synthesis of compound 3b (B) Overlaid FT-IR spectra of fresh and recycled DES To assess the feasibility of this methodology for industrial applications, we performed a gram scale experiment. For this purpose, the condensation reaction of 1, 2, 3, 3-tetramethyl indolenium iodide 1b (20 mmol) and squaric acid 2 (10 mmol) in 50 ml of DES at 80 oC was


13


Page 14 of 28

performed to afford 65 % of compound 3b. This result demonstrated that the present protocol can be utilized for multigram scale synthesis of symmetrical squaraines. For a green chemical reaction, the environmental factor (E-factor) should be low. Therefore, to check the environmental suitability of the present protocol, we have quantified the E-factor for the model reaction involving synthesis of 3b45-46 and compared with the E-factor of reported method involving same reaction44. Interestingly, our developed method showed the low E-factor value of 0.2050 as compared to reported method (E-factor =1.4387), demonstrating environmental acceptability of the present protocol (refer the Supporting Information for calculations, page S38). On the basis of the reported mechanism under classical reaction condition47 and choline chloride: urea based deep eutectic solvent catalyzed reactions48-51, a plausible mechanism for the synthesis of symmetrical squaraines in DES is depicted in Scheme 1. We supposed that, the ChCl: urea DES had two functions (1) to activate carbonyl group of squaric acid via hydrogen binding to increase its electrophilicity (2) to abstract an acidic proton of indolenine to form the corresponding carbanion. First, the deep eutectic solvent might stabilize the carbonyl group of squaric acid I via hydrogen bonding. On the other hand, Lewis basic sites of urea can activate indolenine C-H bond so that acidic proton abstracted by DES to form carbanion II. Next, the formed nucleophilic carbanion II attacks on the electrophilic carbon of squaric acid I which on dehydration gives semisquaraine intermediate III. Finally, the attack of the second carbanion of indolenine IV on semisquaraine intermediate III with the removal of second water molecule furnishes final symmetrical squaraine (Scheme 1).


14

Page 15 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60



15


Page 16 of 28

Scheme 1: The proposed reaction mechanism for the synthesis of symmetrical squaraines using DES


16

Page 17 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Further, we have also studied the photophysical properties of synthesized squaraines 3a-o in chloroform at room temperature using 1 uM concentration. Figure 2 exhibits the UV-Visible absorption spectra and normalized emission spectra of these squaraines in chloroform. Table 3 displays the primary photophysical parameters such as absorption maxima, FWHM (full width at half maximum), emission maxima, Stokes shift, optical band gap (∆Eopt), oscillator strength (f) and transition dipole moment (µeg) of the synthesized squaraines.

Figure 2: (A) UV-Visible absorption spectra (B) normalized emission spectra of the synthesized squaraines 3a-o in chloroform (c = 1 x 10-6 M). As all compounds are blue to green in color, they displayed an intense absorption maxima within the range of 632 -684 nm (NIR region) and emission in the range of 642-704 nm. The substituents at the C-5 position of indolenine moiety profoundly affects the absorption and emission maxima of these squaraine dyes. Thus, the introduction of the weak electron accepting bromo group at the C-5 position of indolenine produced a small red shift of 8 nm in absorption spectra of squaraine dye 3f (λmax = 662 nm) as compared to parent C-5 unsubstituted dye 3a (λmax


17


Page 18 of 28

= 654 nm) (Table 3, entry 6). Moreover, introduction of a strong electron accepting nitro group produced a large red shift of 32 nm in the absorption spectra of squaraine dye 3m (λmax = 676 nm) (Table 3, entry 13). Additionally, the unquaternized indolenine based squaraines (3a, 3f, 3i, 3m) gave a large red shifted absorption (~ 22 nm) compared to its quaternized ones (Table 3, entries 1,6,9,13) and N-substitution on indolenine from methyl to hexyl group produced the negligible contribution in absorption shifts (Table 3, entries 1-5). A similar trend was observed in emission properties of these dyes (Table 3, entries 1-15). It also appears that the optical band gap (∆Eopt) of these dyes reduced on the introduction of electron accepting group at the C-5 position of indolenine moiety. For example, ∆Eopt of squaraine 3a was found to be 1.79 eV. Introduction of nitro group on squaraine 3m reduced the ∆Eopt to 1.71 eV (Table 3, entries 1, 13).

Furthermore, the quaternized indolenine based squaraines exhibited higher oscillator

strength as well as transition dipole moment in comparison to their quaternized counterparts (Table 3, entries 1-15). Table 3: Spectroscopic data for squaraines 3a-o in chloroform at concentration 1 x 10-6 M Entry

compound

λabsa

Log εb

FWHMc

(nm)

λonsetd

∆Eopte

λemf

λsg

(nm)

(eV)

(nm)

(nm)

fh

µegi (Debye)

1

3a

65439

5.55

35.04

693.92

1.79

670

16

0.351

7.00

2

3b

63237,44

5.66

29.99

667.60

1.86

642

10

0.433

7.63

3

3c

63439,4

5.70

28.37

669.71

1.85

643

09

0.580

8.85

4

3d

63637

5.72

28.66

681.26

1.82

646

10

0.461

7.96

5

3e

637

5.70

24.28

669.71

1.85

648

11

0.386

7.23

6

3f

662

5.63

35.82

697.03

1.78

679

17

0.442

7.90

7

3g

640

5.71

29.65

677.04

1.83

651

11

0.466

7.97


18

Page 19 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

a


8

3h

642

5.77

28.86

678.04

1.83

653

11

0.586

8.95

9

3i

684

5.68

38.55

730.80

1.70

704

20

0.480

8.36

10

3j

664

5.69

30.88

706.59

1.75

672

08

0.491

8.39

11

3k

66517

5.72

32.03

707.59

1.75

675

10

0.704

9.98

12

3l

666

5.70

26.83

701.26

1.77

680

14

0.411

7.63

13

3m

67652

5.49

38.55

723.36

1.71

693

17

0.339

6.99

14

3n

66444,52

5.52

31.63

696.03

1.78

678

14

0.346

7.11

15

3o

666

5.60

32.25

698.14

1.78

681

15

0.376

7.30

absorption maximum at molar concentration 1 x 10-6 M, -6

b

molar extinction coefficient determined from

c

absorbance for molar concentration 1 x 10 M, full width at half maximum, donset absorption edge at a higher wavelength., eoptical band gap, ∆Eopt = 1240 x λonset, f emission at molar concentration 1 x 10- 6 M.,

g

shift, hoscillator strength, itransition dipole moment

CONCLUSION In summary, we have demonstrated an environmentally benign synthesis of NIR fluorescent indolenine based symmetrical squaraines in choline chloride-urea deep eutectic solvent for the first time. The developed method has many advantages compared to those reported in literature including being environmentally more benign, operational simplicity, avoidance of organic solvents and organic bases, low reaction temperature, ease of product isolation, higher yield in short reaction time, recyclability of the reaction medium, low environmental factor (E-factor) and easy amenability of the protocol for the large scale synthesis. As far as we know, this is the most efficient approach for the synthesis of symmetrical squaraines. We hope that our green and sustainable protocol can be adopted as a promising alternative way for the industrial synthesis of squaraine colorants.


19

stokes


Page 20 of 28

ASSOCIATED CONTENT Supporting Information General information, experimental procedures, characterization data of products 3a-o, 1

H NMR, 13C NMR, FT-IR and ESI-MS spectra of products 3a-o, 1H NMR spectra of fresh and

recycled DES, Environmental factor (E-factor) calculations.

AUTHOR INFORMATION Corresponding Author * Ganapati Shankarling Department of Dyestuff Technology, Institute of Chemical Technology, N. P. Marg, Matunga, Mumbai - 400019, Maharashtra, India Tel.: 91-22-33612708; fax: +91-22-33611020, e-mail: [email protected]

ACKNOWLEDGMENT Author S.S.K is thankful to AICTE for providing financial assistance and author S.S.D is thankful to Technical Education Quality Improvement Programme (TEQIP)-phase II for the financial grant


20

Page 21 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


REFERENCES (1) Sreejith, S.; Carol, P.; Chithra, P.; Ajayaghosh, A. Squaraine dyes: a mine of molecular materials. J. Mater. Chem. 2008, 18(3), 264–274. DOI 10.1039/B707734C. (2) Law, KY. Squaraine chemistry: Effects of structural changes on the absorption and multiple fluorescence emission of bis [4-(dimethylamino) phenyl] squaraine and its derivative. J Phys Chem .1987, 91, 5184–93. DOI 10.1017/CBO9781107415324.004. (3) Ohsedo, Y.; Miyamoto, M.; Tanaka, A.; Watanabe, H. Synthesis and electrochemical properties of symmetric squarylium dyes containing diarylamine. Dye Pigment. 2014, 101, 261–9. DOI 10.1016/j.dyepig.2013.09.047. (4) Wang, B.; Fan, J.; Sun, S.; Wang, L.; Song, B.; Peng, X. 1-(Carbamoylmethyl)-3H-indolium squaraine dyes: Synthesis, spectra, photo-stability and association with BSA. Dye Pigment .2010, 85, 43–50. DOI 10.1016/j.dyepig.2009.10.002. (5) Ananda Rao, B.; Kim, H.; Son, YA. Synthesis of near-infrared absorbing pyrylium-squaraine dye for selective detection of Hg2+. Sensors Actuators B Chem. 2013, 188, 847–56. DOI 10.1016/j.snb.2013.07.073. (6) Inoue, T.; Pandey, SS.; Fujikawa, N.; Yamaguchi, Y.; Hayase, S. Synthesis and characterization of squaric acid based NIR dyes for their application towards dye-sensitized solar

cells.

J

Photochem

Photobiol

A

Chem.

2010,

213,

23–9.

DOI

10.1016/j.jphotochem.2010.04.015.


21


Page 22 of 28

(7) Prostota, Y.; Kachkovsky, OD.; Reis, LV.; Santos, PF. New unsymmetrical squaraine dyes derived from imidazo [1, 5-a] pyridine. Dye Pigment. 2013, 96,554–62. DOI 10.1016/j.dyepig.2012.10.006. (8) Kim, SH.; Han, SK.; Kim, JJ.; Hwang, SH.; Yoon, CM.; Keum, SR. Synthesis, characteristics and electrophotographic properties of new dithiosquarylium dyes. Dye Pigment. 1998, 39, 77–87. DOI 10.1016/S0143-7208(97)00079-X. (9) Markova, LI.; Terpetschnig, EA.; Patsenker, LD. Comparison of a series of hydrophilic squaraine and cyanine dyes for use as biological labels. Dye Pigment. 2013, 99, 561–70. DOI 10.1016/j.dyepig.2013.06.022. (10)

Beverina, L.; Crippa, M.; Salice, P.; Ruffo, R.; Ferrante, C.; Fortunati, I. Indolic

squaraines as two-photon absorbing dyes in the visible region : X-ray structure, electrochemical and nonlinear optical characterization. Chem. Mater. 2008, 20, 3242–3244. DOI: 10.1021/cm800714k. (11)

Emmelius, M.; Pawlowski, G.; Vollmann, HW. Materials for optical data storage.

Angewandte Cheme. 1989, 28, 1445-1466. DOI org/10.1002/anie.198914453. (12) Chung, S.; Zheng, S.; Odani, T.; Beverina, L.; Fu, J.; Padilha, LA. Extended squaraine dyes with large two-photon absorption cross-sections. J. Am. Chem. Soc. 2006, 14444–45. DOI 10.1021/ja065556m. (13) Ahn, HY.; Yao, S.; Wang, X.; Belfield, KD. Near-infrared-emitting squaraine dyes with high 2PA cross-sections for multiphoton fluorescence imaging. ACS Appl Mater Interfaces. 2012, 4, 2847–54. DOI 10.1021/am300467w.


22

Page 23 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(14) Law, KY. Squaraine chemistry: Design, synthesis and xerographic properties of a highly sensitive unsymmetrical fluorinated squaraine. Chem Mater. 1992, 4, 605–11. DOI 10.1021/cm00021a020. (15) Ishchenko, AA.; Kozinets, AV.; Kostenko, LI.; Kurdyukova, IV.; Mokrinskaya, EV.; Studzinskii, SV.;

Chuprina, NG. Sensitization of photoconductivity in ferrocene-

containing oligomer by squarylium and merocyanine dyes. Journal of Applied Spectroscopy. 2011, 78,129-133. DOI 10.1007/s10812-011-9435-8. (16) Smits, ECP.; Setayesh, S.; Anthopoulos, TD.; Buechel, M.; Nijssen, W.; Coehoorn, R. Near-infrared light-emitting ambipolar organic field-effect transistors. Adv Mater. 2007, 19, 734–8. DOI 10.1002/adma.200600999. (17) Kuster, S.; Geiger, T. Strategies and investigations on bridging squaraine dye units. Dye Pigment. 2012, 95, 657–70. DOI 10.1016/j.dyepig.2012.06.017. (18) Mayerhöffer, U.; Gsänger, M.; Stolte, M.; Fimmel, B.; Würthner, F. Synthesis and molecular properties of acceptor-substituted squaraine dyes. Chem - A Eur J. 2013, 19, 218–32. DOI 10.1002/chem.201202783. (19) Ohira, S.; Rudra, I.; Schmidt, K.; Barlow, S.; Chung, SJ.; Zhang, Q. Electronic and vibronic contributions to two-photon absorption in donor-acceptor-donor squaraine chromophores. Chemistry. 2008, 14, 11082–91. DOI 10.1002/chem.200801055. (20) Reis, L.; Serrano, J.; Almeida, P.; Santos, P. The synthesis and characterization of novel aza-substituted squarylium cyanine dyes. Dye Pigment. 2009, 81, 197–202. DOI 10.1016/j.dyepig.2008.10.001.


23


(21) Barbero, N.; Magistris, C.;

Park,

J.; Saccone, D.;

Page 24 of 28

Quagliotto, P.; Buscaino, R.

Microwave-assisted synthesis of near-infrared fluorescent indole-based squaraines. Org Lett. 2015, 17, 3306–9. DOI 10.1021/acs.orglett.5b01453. (22) Kafle, A.; Handy, ST. A one-pot, copper-catalyzed azidation/click reaction of aryl and heteroaryl bromides in an environmentally friendly deep eutectic solvent. Tetrahedron .2017, 73, 7024–9. DOI 10.1016/j.tet.2017.10.050. (23) Merza, F.; Fawzy, A.; AlNashef, I.; Al-Zuhair, S.; Taher H. Effectiveness of using deep eutectic solvents as an alternative to conventional solvents in enzymatic biodiesel production

from

waste

oils.

Energy

Reports.

2018,

4,

77–83.DOI

10.1016/j.egyr.2018.01.005. (24) Liu, Y.; Friesen, JB.; McAlpine, JB.; Lankin, DC.; Chen, SN.; Pauli GF. Natural deep eutectic solvents: Properties, applications and perspectives. J Nat Prod. 2018, 81, 679–90. DOI 10.1021/acs.jnatprod.7b00945. (25) Phadtare, SB.; Jarag, KJ.; Shankarling, GS. Greener protocol for one pot synthesis of coumarin styryl dyes. Dye Pigment. 2013, 97, 105–12. DOI 10.1016/j.dyepig.2012.12.001. (26) Azizi, N.; Dezfooli, S.; Mahmoudi, M. Greener synthesis of spirooxindole in deep eutectic solvent. J Mol Liq. 2014, 194, 62–7. DOI 10.1016/j.molliq.2014.01.009. (27) Azizi, N.; Mariami, M.; Edrisi, M. Greener construction of 4H-chromenes based dyes in deep

eutectic

solvent.

Dye

Pigment.

2014,

100,

215–21.

DOI

10.1016/j.dyepig.2013.09.007. (28) Shaabani, A.; Hooshmand, SE.; Tabatabaei, AT. Synthesis of fully substituted naphthyridines: A novel domino four-component reaction in a deep eutectic solvent system


24

Page 25 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


based

on

choline

chloride/urea.

Tetrahedron

Lett.

2016,

57,

351–3.

DOI

10.1016/j.tetlet.2015.12.017. (29) Sanap, AK.; Shankarling, GS. Eco-friendly and recyclable media for rapid synthesis of tricyanovinylated aromatics using biocatalyst and deep eutectic solvent. Catal Commun. 2014, 49, 58–62. DOI 10.1016/j.catcom.2014.01.031. (30) Singh, BS.; Lobo, HR.; Pinjari, DV.; Jarag, KJ.; Pandit, AB.; Shankarling, GS. Ultrasound and deep eutectic solvent (DES): A novel blend of techniques for rapid and energy efficient synthesis

of

oxazoles.

Ultrason

Sonochem.

2013,

20,

287–93.

DOI

10.1016/j.ultsonch.2012.06.003. (31) Yadav, UN.; Shankarling, GS. Synergistic effect of ultrasound and deep eutectic solvent choline chloride-urea as versatile catalyst for rapid synthesis of β-functionalized ketonic derivatives. J Mol Liq. 2014, 195, 188–93. DOI 10.1016/j.molliq.2014.02.016. (32) Abbott, AP.; Capper , G.; Davies, DL.; Rasheed, RK.; Tambyrajah, V. Novel solvent properties of choline chloride/urea mixtures. Chem Commun. 2003, 70–1. DOI 10.1039/b210714g. (33) Owens, EA.; Bruschi, N.; Tawney, JG.; Henary, M. A microwave-assisted and environmentally benign approach to the synthesis of near-infrared fluorescent pentamethine cyanine dyes. Dye Pigment. 2015, 113, 27–37. DOI 10.1016/j.dyepig.2014.07.035. (34) Balmond, EI.; Tautges, BK.; Faulkner, AL.; Or, VW.; Hodur, BM.; Shaw, JT. Comparative evaluation of substituent effect on the photochromic properties of spiropyrans and spirooxazines. J Org Chem. 2016, 81, 8744–58. DOI 10.1021/acs.joc.6b01193. (35) Lee, EM.; Gwon, SY.; Son, YA.; Kim, SH. Squarylium-based chromogenic anion sensors. Spectrochim Acta A Mol Biomol Spectrosc. 2012, 95, 25–8.DOI 10.1016/j.saa.2012.04.080.


25


Page 26 of 28

(36) Wang, C.; Xue, S.; Liang, Q.; Li, Z.; Xu, S. High selective and sensitive colorimetric and fluorescent chemosensor of Fe3+ and Cu2+ based on 2, 3, 3-trimethylnaphto [1, 2-d] squaraine. RSC Advances. 2016, 6, 6540-6550. DOI: 10.1039/c5ra22530b. (37) Matsui, M.; Fukushima, M.; Kubota, Y.; Funabiki, K.; Shiro, M. Solid-state fluorescence of squarylium dyes. Tetrahedron. 2012, 68, 1931–5. DOI 10.1016/j.tet.2011.12.067. (38) Santos, PF.; Reis, LV.; Almeida, P.; Oliveira, AS.; Ferreira, LFV. Singlet oxygen generation ability of squarylium cyanine dyes. J Photochem Photobiol A Chem. 2003, 160, 159–61. DOI 10.1016/S1010-6030(03)00203-X. (39) Kim, SH.; Hwang, SH. Electrochromic properties of functional squarylium dyes. Dye Pigment. 1998, 36, 139–48. DOI 10.1016/S0143-7208(97)00006-5. (40) Serpe, L.; Ellena, S.; Barbero, N.; Foglietta, F.; Prandini, F.; Gallo, MP. Squaraines bearing halogenated moieties as anticancer photosensitizers: Synthesis, characterization and biological

evaluation.

Eur

J

Med

Chem.

2016,

113,

187–97.

DOI

10.1016/j.ejmech.2016.02.035. (41) Fuhrmann, G.; Nelles, G.; Zilai, AB.; Yasuda, A.Dye including an anchoring group in its molecular structure. U.S. Patent US2010212737A1, Aug 26, 2010. (42) Miltsov, S.; Encinas, C.; Alonso, J. New cyanine dyes: Norindosquarocyanines. Tetrahedron Lett. 1999, 40, 4067–8. DOI 10.1016/S0040-4039(99)00650-4. (43) Burke, A.; Schmidt-Mende , L.; Ito, S.; Grätzel M. A novel blue dye for near-IR “dyesensitised” solar cell applications. Chem Commun. 2007, 234–6. DOI 10.1039/b609266g. (44) Kim, SH.; Hwang, SH. Synthesis and photostability of functional squarylium dyes. Dye Pigment. 1997, 35, 111–21. DOI 10.1016/S0143-7208(96)00101-5.


26

Page 27 of 28 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(45) Van Aken, K.; Strekowski, L.; Patiny, L. EcoScale, a semi-quantitative tool to select an organic preparation based on economical and ecological parameters. Beilstein J Org Chem. 2006, 2, 1–7. DOI 10.1186/1860-5397-2-3. (46) Jejurkar ,VP.; Khatri, CK.; Chaturbhuj, GU.; Saha, S. Environmentally benign, highly efficient and expeditious solvent-free synthesis of trisubstituted methanes catalyzed by sulfated polyborate. Chemistry Select. 2017, 2, 11693–6. DOI 10.1002/slct.201702610. (47) Sprenger, HE.; Ziegenbein, W.cyclobutendiylium dyes. Angewandte Cheme. 1968, 7, 530535. DOI org/10.1002/anie.196805301. (48) Khandelwal, S.; Tailor, YK.; Kumar, M. Deep eutectic solvents (DESs) as eco-friendly and sustainable solvent/catalyst systems in organic transformations. J Mol Liq. 2016, 215, 345– 86. DOI 10.1016/j.molliq.2015.12.015. (49) Bhosle, MR.; Khillare, LD.; Dhumal, ST.; Mane, RA. A facile synthesis of 6-amino-2H, 4H-pyrano [2, 3-c] pyrazole-5-carbonitriles in deep eutectic solvent. Chinese Chem Lett. 2016, 27, 370–4. DOI 10.1016/j.cclet.2015.12.005. (50) Azizi, N.; Ahooie, TS.; Hashemi, MM. Multicomponent domino reactions in deep eutectic solvent: An efficient strategy to synthesize multisubstituted cyclohexa-1, 3-dienamines. J Mol Liq .2017, 246, 221–4. DOI 10.1016/j.molliq.2017.09.049. (51) Azizi, N.; Dezfooli, S.; Khajeh, M.; Hashemi, MM. Efficient deep eutectic solvents catalyzed synthesis of pyran and benzopyran derivatives. J Mol Liq. 2013, 186, 76–80. DOI 10.1016/j.molliq.2013.05.011. (52) Hwang, SH.; Kim, NK.; Koh, KN.; Kim, SH. Absorption Spectra and electrophotographic properties of squarylium dyes containing a nitro group. Dye Pigment .1998, 39, 359–69. DOI 10.1016/S0143-7208(98)00021-7.


27


Page 28 of 28

Table of contents

Synopsis The first time green synthesis of NIR absorbing indolenine based symmetrical squaraines has been developed by using choline chloride-urea deep eutectic solvent


28

Greener Protocol for the Synthesis of NIR Fluorescent Indolenine

Recommend Documents