Supporting Information for

Microwave-Assisted Synthesis of Near-Infrared Fluorescent

Indole-Based Squaraines
Nadia Barbero,† Claudio Magistris,† Jinhyung Park,† Davide Saccone,† Pierluigi Quagliotto,†
Roberto Buscaino,† Claudio Medana,‡ Claudia Barolo*,† and Guido Viscardi†
† Department of Chemistry and NIS Interdepartmental Centre and ‡ Dipartimento di Biotecnologie
Molecolari e Scienze per la Salute, University of Torino, via Giuria 7, I-10125 Torino, Italy

* E-mail: claudia.barolo@unito.it

Table of Contents:

Figure S1. Absorbance and fluorescence spectra of the synthesized squaraines S2

Scheme S1: Synthesis of 5-Bromo-2,3,3-trimethyl-3H-indole S2
Table S1: Design of Experiments on the quaternization synthesis S3
Figure S2: Isodensity plot of D-Optimal Design for the synthesis of 2e S4
Table S2. General quaternization synthesis of indolenines and benzoindolenines S4-S5
Figure S3: Comparison between classical and microwave synthesis S6
Table S3. Reaction scheme for hemisquarates preparation S7
Scheme S2: Synthesis of unsymmetrical squaraine SQ01 S7
Structures of the intermediates and squaraines synthesized S8-S9
General experimental S10
General procedure for quaternarized salts synthesis S10
General procedure for symmetrical squaraines synthesis S12
General procedure for unsymmetrical squaraines synthesis S19
Comments on the reproducibility of MW reactions S22
1
H and 13C NMR spectra of the synthesized compounds S23

S1
 1.0 VG0 1.0
VG1-C2
VG1-C8

Normalized fluorescence
0.8 VG1-C10 0.8
VG1-H6

Normalized Abs
VG5
0.6 VG10-C2 0.6
VG10-C8

0.4 0.4

0.2 0.2

0.0 0.0
510 540 570 600 630 660 690 720 750 780 810 840 870 900
Wavelength (nm)

Figure S1. Absorbance (solid lines) and fluorescence (dash lines) spectra of the synthesized squaraines.

HCl
H2N O N
NH
I C4H9
ACN
Br N
AcOH C4H9
MW 155°C,60min
MW 10 min 160°C I
Br Br

Scheme S1: Synthesis of 5-Bromo-2,3,3-trimethyl-3H-indole.

S2
 Table S1: Design of Experiments on the quaternization synthesis

entry time temperature indolenine/iodide* indolenine/solvent**

R yield
(compound) (minutes) (°C) (mol/mol) (mol/mol)
1 (2d) C8H17 10 140 1/4 1/16 22
2 (2d) C8H17 10 170 1/4 1/16 55
3 (2d) C8H17 25 140 1/4 1/16 47
4 (2d) C8H17 25 170 1/4 1/16 35
5 (2d) C8H17 10 140 1/4 solventless 0
6 (2d) C8H17 10 170 1/4 solventless 12
7 (2d) C8H17 25 140 1/4 solventless 0
8 (2d) C8H17 25 170 1/4 solventless 16
9 (2d) C8H17 18 155 1/4 1/16 61
10 (2d) C8H17 18 155 1/4 1/16 61
11 (2d) C8H17 18 155 1/4 1/16 59
12 (2d) C8H17 18 155 1/4 1/8 50
13 (2d) C8H17 25 155 1/4 1/16 62
14 (2d) C8H17 5 185 1/4 1/16 45
15 (2e) C10H21 60 155 1/8 1/3 36
16 (2e) C10H21 20 180 1/8 1/3 15
17 (2e) C10H21 60 180 1/4 solventless 30
18 (2e) C10H21 40 168 1/6 1/4 37
19 (2e) C10H21 20 180 1/7 solventless 5
20 (2e) C10H21 47 155 1/8 1/8 73
21 (2e) C10H21 60 180 1/8 solventless 5
22 (2e) C10H21 33 180 1/8 1/8 1
23 (2e) C10H21 60 155 1/4 1/5 64
24 (2e) C10H21 33 155 1/8 solventless 7
25 (2e) C10H21 40 168 1/6 1/4 32
26 (2e) C10H21 60 163 1/8 1/8 22
27 (2e) C10H21 20 172 1/8 1/8 41
28 (2e) C10H21 20 155 1/8 1/5 34
29 (2e) C10H21 47 155 1/4 solventless 1
30 (2e) C10H21 20 180 1/4 solventless 7
31 (2e) C10H21 60 172 1/4 1/8 7
32 (2e) C10H21 20 163 1/8 solventless 8
33 (2e) C10H21 33 155 1/4 1/8 36
34 (2e) C10H21 60 155 1/5 solventless 3
35 (2e) C10H21 40 168 1/6 1/4 25
36 (2e) C10H21 60 180 1/8 1/5 -
37 (2e) C10H21 60 180 1/5 1/8 -
38 (2e) C10H21 40 168 1/6 1/4 20
39 (2e) C10H21 20 180 1/4 1/8 18
40 (2e) C10H21 20 155 1/7 1/8 12
41 (2e) C10H21 20 155 1/4 solventless -
42 (2e) C10H21 60 155 1/8 1/8 59
43 (2e) C10H21 60 155 1/8 1/5 51
44 (2e) C10H21 47 155 1/8 1/5 40
45 (2e) C10H21 40 155 1/4 1/5 65
46 (2e) C10H21 40 155 1/4 1/5 63
47 (2e) C10H21 40 155 1/2 1/5 63
48 (2e) C10H21 40 155 1/3 1/5 58
49 (2e) C10H21 40 155 1/3 1/5 59
* entries 1-14: C8H17I, entries 15-49: C10H21I; ** CH3CN
S3
 A three dimensional diagram with the main parameters (temperature, ratio of solvent and yield) was
obtained. The isodensity section corresponding to a ratio solvent to reagent of 5 is represented, confirming
that the maximum yield is obtained at 155 °C. The obtained results outperformed the software predictions;
the highest yield (65%) was obtained with 40 min heating at 155 °C, with large excess of both iodide and
solvent.

Figure S2: Isodensity plot of D-Optimal Design for the synthesis of 2e.

Table S2. General quaternization synthesis of indolenines and benzoindolenines.

S4
 entry time yield
Y R method
(compound) min (%)
1 (3a) H C2H5 A 1440 591
2 (3a) H C2H5 A 1440 892
3 (3a) H C2H5 A 1440 913
4 (3a) H C2H5 B 9 91
5 (3b) COOH C2H5 A 1440 794
6 (3b) COOH C2H5 A 600 685
7 (3b) COOH C2H5 B 20 94
8 (3c) COOH C4H9 A 2880 776
9 (3c) COOH C4H9 B 20 86
10 (3d) COOH C8H17 A 660 757
11 (3d) COOH C8H17 B 25 66
12 (3e) COOH C10H21 A 1440 538,9
13 (3e) COOH C10H21 Aa 1200 21
14 (3e) COOH C10H21 B 30 70
15 (3f) COOH C6H9 A - -
16 (3f) COOH C6H9 B 35 40
17 (3g) Br C2H5 A 2400 8710
18 (3g) Br C2H5 B 40 61
19 (3h) Br C4H9 A 4320 7811
20 (3h) Br C4H9 B 60 68
21 (3i) Br C12H25 A 7200 7812
22 (3i) Br C12H25 B 60 46
23 (5a) COOH C2H5 A - -
24 (5a) COOH C2H5 B 40 7713
25 (5b) COOH C8H17 A - -
3
26 (5b) COOH C8H17 B 40 511

Method A: conventional heating, anhydrous conditions; Method B: MW; Method Aa: conventional heating,
without anhydrous conditions.

1
Pardal, A. C.; Ramos, S. S.; Santos, P. F.; Reis, L. V; Almeida, P.; Codex, V. R. Molecules 2002, 7, 320–330
2
Chang, C. H.; Chen, Y. C.; Hsu, C. Y.; Chou, H. H.; Lin, J. T. Org. Lett. 2012, 14, 4726–4729
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4
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275
5
Gräf, K.; Rahim, M.; Das, S.; Thelakkat, M. Dye. Pigment. 2013, 99, 1101–1106
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Pandey, S. S.; Inoue, T.; Fujikawa, N.; Yamaguchi, Y.; Hayase, S. Thin Solid Films 2010, 519, 1066–1071
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Yum, J.-H.; Walter, P.; Huber, S.; Rentsch, D.; Geiger, T.; Nüesch, F.; De Angelis, F.; Grätzel, M.; Nazeeruddin, M.
K. J. Am. Chem. Soc. 2007, 129, 10320–10321
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Venditti, I.; Barbero, N.; Russo, V.; M.; Di Carlo, A.; Decker, F.; Fratoddi, I.; Barolo, C.; Dini, D. Mater. Res.
Express 2014, 1, 015040
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(a) Martiniani, S.; Anderson, A. Y.; Law, C.; O’Regan, B. C.; Barolo, C. Chem. Commun. 2012, 48, 2406–2408. (b)
Etgar, L.; Park, J.; Barolo, C.; Lesnyak, V.; Panda, S. K.; Quagliotto, P.; Hickey, S. G.; Nazeeruddin, M. K.;
Eychmüller, A.; Viscardi, G.; Grätzel, M. RSC Adv. 2012, 2, 2748.
10
Reddington, M. V. Bioconjug. Chem. 2007, 18, 2178–2190
11
Levitz, A.; Ladani, S. T.; Hamelberg, D.; Henary, M. Dye. Pigment. 2014, 105, 238–249
12
Shi, Y.; Hill, R. B. M.; Yum, J.-H.; Dualeh, A.; Barlow, S.; Grätzel, M.; Marder, S. R.; Nazeeruddin, M. K. Angew.
Chem. Int. Ed. Engl. 2011, 50, 6619–6621
13
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Nazeeruddin, Md. K.; Barolo C.; Viscardi G. Phys. Chem. Chem. Phys. 2014, 16, 24173-24177
S5
 T=130°C T=160°C
t=6 h t=40’
yield=32% yield=85%

Figure S3: Comparison between the classical and MW synthesis of a squaraine: NMR of raw products after
precipitation from the reaction mixture (squaraine VG1-C10)

S6
Table S3. Reaction scheme for hemisquarates preparation.

entry time yield

R method
(compound) (min) (%)
1 (6a) C2H5 A 15 88
2 (6a) C2H5 B * *
3 (6b) C8H17 A 900 7414
4 (6b) C8H17 B 45 88
5 (6c) C10H21 A - -
6 (6c) C10H21 B 50 75
7 (7) C8H17 A 1200 4713
8 (7) C8H17 B 50 49

Method A: classical heating, B: MW heating. The procedure consists of a reaction between quaternarized
carboxyindolenine and diethylsquarate in presence of N,N,N-triethylamine (TEA) with the following molar
ratio: 1:2:3
* The reaction directly affords the symmetrical squaraine VG1-C2

Scheme S2: Synthesis of unsymmetrical squaraine SQ01: a) general procedure reported in literature and b)
modified procedure of the present paper.

14
Kuster, S.; Sauvage, F.; Nazeeruddin, Md. K.; Grätzel, M.; Nüesch, F. A.; Geiger, T. Dyes Pigm. 2010, 87, 30-38
S7
 Br HOOC HOOC
I
N N I N I N
I C4H9

1 2a 3a 3b 3c

HOOC HOOC HOOC

N I N I N I
C8H17 C10H21
3d 3e 3f

Br Br Br

N I N N
C4H9 I C12H25
I

3g 3h 3i

HOOC HOOC

N I N I
C8H17
5a 5b

R R
N N
Y O
O
Y
Y O Y
O

N N
VG1 series VG10 series
R R

Y=H R=H SQ-NH

Y = Br R=H Br-NH Y = COOH R= C2H5 VG10-C2
Y=H R = C2H5 R1 Y = COOH R= C8H17 VG10-C8
Y = COOH R = C2H5 VG1-C2
Y = Br R = C2H5 Br-C2
Y = Br R = C4H9 Br-C4
Y = COOH R = C8H17 VG1-C8
Y = COOH R = C10H21 VG1-C10
Y = COOH R = C12H25 VG1-C12
Y = Br R = C12H25 Br-C12
Y = COOH R = C6H9 VG1-H6

NC CN
NC
H
O CN N

O O N N R OR N

8 Y Y

Y = COOH R = C4H9 VG2-C4

Y = Br R = C2H5 VG2-Br

Scheme S3. Structures of the synthesized symmetrical squaraines and relative intermediates.

S8
 O O O O O O

HOOC HOOC HOOC

O O O
N N N
C10H21
C8H17
6a 6b 6c

R2
HOOC O O N

O
Y
O
HOOC
N O
C8H17 N
R1
7
Y=H R1 = C8H17 R2 = C2H5 SQ01
Y = COOH R1 = C6H9 R2 = C2H5 VG1-C2-H6
Y = COOH R1 = C6H9 R2 = C8H17 VG1-C8-H6
Y = COOH R1 = C6H9 R2 = C10H21 VG1-C10-H6

C2H5
N
HOOC O O
HOOC
N N
O
O
C7H15
N
C8H17

VG13 VG5

Scheme S4. Structures of the synthesized unsymmetrical squaraines and relative intermediates.

S9
General experimental

All the chemicals were purchased from Sigma Aldrich, except for 5-Carboxy-2,3,3-trimethyl-3H-indolium
iodide which was purchased from Intatrade Chemicals GmbH, and were used without any further
purification.
All microwave reactions were performed in single-mode Biotage Initiator 2.5. TLC were performed on silica
gel 60 F254 plates. Column chromatography was performed on a Biotage Isolera flash purification system.
GC-MS spectra were recorded on a Thermo Finnigan Trace GC with a cross-linked methyl silicone capillary
column, coupled to a Thermo Finnigan Trace MS mass spectrometer equipped with an electronic impact
source (EI). LC-HRMS analyses were accomplished with an Ultimate 3000 HPLC instrument (Dionex,
Milan, Italy) coupled to an LTQ Orbitrap instrument at a resolution of 30000 (500 m/z FWHM) in FTMS
mode (Thermo Scientific, Rodano, Italy) with an APCI interface. UV-Vis spectra were recorded on a
Shimadzu UV-1700 spectrometer. 1H NMR (200 MHz) and 13C NMR (50 MHz) spectra were recorded on a
Bruker Avance 200 NMR.
The intermediates 1,1,2-trimethyl-1H-benzo[e]indole-7-carboxylic acid,13 5-Carboxy-1-dodecyl-2,3,3-
trimethyl-3H-indolium iodide,4 1-ethyl-2-methylbenz[cd]indolium perchlorate15 and 3-ethyl-1,1,2-trimethyl-
1H-benzo[e]indoleninium iodide16 were prepared as described in literature.

6-Iodo-1-hexyne (1): 6-Chloro-1-hexyne (1.00 g, 8.6 mmol), NaI (1.40 g, 9.3 mmol) and acetone (10 mL)
were introduced in a microwave reaction vial which was sealed with a crimp cap and heated in microwave
system at 140 oC for 60 min, when GC-MS showed reaction completion; solvent evaporation afforded a
viscous solid which was treated with CH2Cl2 and filtered; evaporation of the solution gave the pure title
compound as yellow-brown oil (g 1.70, yield = 95%)17,18

5-Bromo-2,3,3-trimethyl-3H-indole (2a) was synthesized with slight modifications from the literature
procedure:19 4-bromophenylhydrazine hydrochloride (1.90 g, 8.5 mmol), 3-methyl-2-butanone (2.5 mL, 23.4
mmol) and glacial acetic acid (15 mL) were introduced in a reaction vial which was sealed and heated at
160°C for 10 min; the volatile components were then removed under vacuum, and the residue was
partitioned between ether (30 mL) and water (100 mL); the aqueous phase was washed again with petroleum
ether (2 x 30 mL) and then the combined organic solutions were rewashed with brine, dried and evaporated
under vacuum to afford 2a (1,88 g, yield = 93%) as a brown orange oil at low viscosity.

Many of the quaternized salts are previously published compounds and the characterizations agree with the
literature values - 3a,3 3b,4 3c,3 3d,7 3e,9b,8 3g,10 3h,11 3i,12 5a,13 5b.13 Anhydrous CH3CN was used for better
purity respect to ACS reagent grade acetonitrile (Sigma Aldrich) but anhydrous conditions are not required
for the reaction.

General procedure for quaternarized salts synthesis: 1-Ethyl-2,3,3-trimethyl-3H-indolium iodide (3a):

2,3,3-trimethylindolenine (0.76 ml, 4.7 mmol) and iodoethane (1.51 ml, 18.8 mmol) were introduced in a
reaction vial which was sealed with a crimp cap and heated in microwave system at 130 °C for 9 min; the
solid was repeatedly washed under stirring with diethyl ether (3 x 100 mL), filtered and then crystallized
with acetonitrile. The product was obtained as violet powder (g 1.35, yield = 91%)
1
H NMR (DMSO-d6): δ = 8.00-7.95 (m, 1H), 7.87-7.83 (m, 1H), 7.65-7.60 (m, 2H), 4.50 (q, J = 7.5 Hz, 2H),
2.83 (s, 3H), 1.53 (s, 6H), 1.44 (t, J = 7.5 Hz, 3H)3

15
Magistris, C.; Martiniani, S.; Barbero, N.; Park, J.; Benzi, C.; Anderson, A.; Law, C.; Barolo, C.; O’Regan, B. Renew.
Energ. 2013, 60, 672-678
16
Kuster, S.; Geiger, T. Dyes Pigm. 2012, 95, 657-670
17
Ahn, S. K.; Ban, T.; Sakthivel, P.; Jin, S.-H.; Gal, Y.S.; Lee J. H. Macromolecular Research 2012, 20, 5, 459-464
18
Jiang, X.-R.; Wang, P.; Smith, C. L.; Zhu, B. T. J. Med. Chem. 2013, 56, 2779−2790
19
Owens, E. A.; Bruschi, N.; Tawney, J. G.; Henary. M. Dyes Pigm. 2015, 113, 27-37
S10
5-Carboxy-1-ethyl-2,3,3-trimethyl-3H-indolium iodide (3b): 5-carboxy-2,3,3-trimethylindolenine (1.98 g,
9.7 mmol), iodoethane (3.12 ml, 38.8 mmol) and 7 ml CH3CN were reacted as described in the general
procedure at 155 °C for 20 min, giving the title compound as yellow powder (g 3.28, yield = 94%)
1
H NMR (DMSO-d6): δ = 8.39 (s, 1H), 8.17-8.07 (m, 2H), 4.53 (m, 2H), 2.89 (s, 3H), 1.58 (s, 6H), 1.45 (m,
3H)4

5-Carboxy-1-butyl-2,3,3-trimethyl-3H-indolium iodide (3c): 5-carboxy-2,3,3-trimethylindolenine (2.50 g,

12.3 mmol), 1-iodobutane (5.6 ml, 49.2 mmol) and 9 ml CH3CN were reacted as described in the general
procedure at 155 °C for 20 min, giving the title compound as pink powder (g 4.10, yield = 86%)
1
H NMR (DMSO-d6): δ = 8.39 (s, 1H), 8.14 (m, 2H), 4.49 (m, 2H), 2.92 (s, 3H), 1.83 (m, 2H), 1.58 (s, 6H),
1.46-1.40 (m, 2H), 0.93 (t, J = 7.5, 3H)3

5-Carboxy-1-octyl-2,3,3-trimethyl-3H-indolium iodide (3d): in a typical experiment, 5-carboxy-2,3,3-

trimethyl indolenine (2.0 g, 9.8 mmol), 1-iodooctane (7.1 mL, 39.2 mmol) and anhydrous CH3CN (8 mL)
were reacted as described in the general procedure at 155 °C for 25 min, giving the title compound as light
pink powder (2.87 g, yield = 66%)
1
H NMR (DMSO-d6): δ = 8.40 (s, 1H), 8.17-8.07 (m, 2H), 4.47 (m, 2H), 2.88 (s, 3H), 1.83 (m, 2H), 1.58 (s,
6H), 1.26-1.20 (m, 10H), 0.84-0.81 (m, 3H)7

5-Carboxy-1-decyl-2,3,3-trimethyl-3H-indolium iodide (3e): 5-carboxy-2,3,3-trimethylindolenine (1.70 g,

8.4 mmol), 1-iododecane (7.2 ml, 33.6 mmol) and 9 ml CH3CN were reacted as described in the general
procedure for 30 min, giving the title compound as pink powder (g 2.78, yield = 70%)
1
H NMR (DMSO-d6): δ = 8.39 (s, 1H), 8.14 (m, 2H), 4.48 (m, 2H), 2.91 (s, 3H), 1.82 (m, 2H), 1.58 (s, 6H),
1.38-1.22 (m, 14H), 0.83 (m, 3H)9b,8

5-Carboxy-1-(hex-5-ynyl)-2,3,3-trimethyl-3H-indolium iodide (3f): 5-carboxy-2,3,3-trimethylindolenine

(0.51 g, 2.5 mmol), 6-iodo-1-hexyne (1, 1.56 g, 7.5 mmol) and 10 ml CH3CN were reacted as described in
the general procedure at 150 °C for 35 min; crystallization with CH3CN afforded the pure title compound as
light pink powder (g 0.41, yield = 40%)
HRMS (ESI) calcd for [M]+ 284.1651, found 284.1694
1
H NMR (DMSO-d6): δ = 8.38 (s, 1H), 8.25-8.10 (m, 2H), 4.53 (m, 2H), 2.92 (s, 3H), 2.82 (s, 1H), 2.26 (t, J
= 6.0 Hz, 2H), 1.93 (m, 2H), 1.75-1.40 (m, 8H)
13
C NMR (CDCl3): δ = 199.7, 166.5, 144.3, 142.3, 131.7, 130.4, 124.4, 115.7, 83.9, 71.8, 54.6, 47.6, 26.3,
24.9, 21.9, 17.4, 14.8

5-Bromo-1-ethyl-2,3,3-trimethyl-3H-indolium iodide (3g): 160 mg of 2a (167 mg, 0.67 mmol),

iodoethane (0.2 mL, 2.5 mmol) and 4 ml CH3CN were reacted as described in the general procedure at 155
°C for 40 min, giving the title compound as white slightly brownish powder (168 mg, 61 % yield).
1
H NMR (DMSO-d6): δ = 8.19 (s, 1H), 7.95 (d, J = 8.0 Hz, 1H), 7.85 (d, J = 8.0 Hz, 1H), 4.48 (q, J = 7.5 Hz,
2H), 2.83 (s, 3H), 1.55 (s, 6H), 1.42 (t, J = 7.5 Hz, 3H)10

5-Bromo-1-butyl-2,3,3-trimethyl-3H-indolium iodide (3h): 2a (500 mg, 2.1 mmol), 1-iodobutane (0.7 mL,
6.3 mmol) and 10 ml anhydrous CH3CN were reacted as described in the general procedure at 155 °C for 60
min, giving the title compound as a brownish solid (603 mg, 68 % yield).
1
H NMR (DMSO-d6): δ = 8.20 (s, 1H), 7.97 (d, J = 8.0 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 4.45 (mt, J = 7.0
Hz, 2H), 2.85 (s, 3H), 1.87-1.72 (m, 2H), 1.55 (s, 6H), 1.47-1.36 (m, 2H), 0.92 (t, J = 7.5 Hz, 3H)11,20

20
Mayerhöffer, U.; Fimmel, B.; Würthner, F.; Angew. Chem. Int. Ed. (English) 2012, 51, 164-167
S11
5-Bromo-1-dodecyl-2,3,3-trimethyl-3H-indolium iodide (3i): 2a (500 mg, 2.1 mmol), 1-iododecane (1.6
mL, 6.3 mmol) and 10 ml anhydrous CH3CN were reacted as described in the general procedure at 155 °C
for 60 min, giving the title compound as white brownish powder (516 mg, 46 % yield)
1
H NMR (DMSO-d6): δ = 8.19 (s, 1H), 7.96 (d, J = 8.0 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 4.43 (t, J = 7.0 Hz,
2H), 2.83 (s, 3H), 1.80 (m, 2H), 1.55 (s, 6H), 1.50-1.20 (m, 18H), 0.85 (t, J = 7.0 Hz, 3H)12

7-Carboxy-3-ethyl-1,1,2-trimethyl-1H-benz[e]indolium iodide (5a): 7-carboxy-1,1,2-trimethyl-1H-

benz[e]indolenine (0.99 g, 3.9 mmol), iodoethane (1.3 mL, 15.6 mmol) and 8 ml CH3CN were reacted as
described in the general procedure for 40 min, giving the title compound as brownish solid (g 1.23, yield =
77%)
1
H NMR (DMSO-d6): δ = 8.88 (s, 1H), 8.50 (t, J = 9.0 Hz, 2H), 8.22 (d, J = 10.0 Hz, 2H), 4.65-4.61 (m, 2H),
2.95 (s, 3H), 1.77 (s, 6H), 1.51 (t, J = 7.0 Hz, 3H)13

7-Carboxy-3-octyl-1,1,2-trimethyl-1H-benz[e]indolium iodide (5b): 7-carboxy-1,1,2-trimethyl-1H-

benz[e]indolenine (0.99 g, 3.9 mmol), 1-iodooctane (2.8 mL, 15.6 mmol) and 8 ml CH3CN were reacted as
described in the general procedure for 40 min, giving the title compound as yellow-brown solid (g 0.98, yield
= 51%)
1
H NMR (DMSO-d6): δ = 8.88 (s, 1H), 8.50 (t, J = 8.0 Hz, 2H), 8.22 (d, J = 10.0 Hz, 2H), 4.58 (m, 2H), 2.96
(s, 3H), 1.89-1.84 (m, 2H), 1.78 (s, 6H), 1.57-1.25 (m, 10H), 0.84 (t, J = 7.0 Hz, 3H)13

Squaraines SQ-NH,21 R1,22 VG1-C2,4 VG1-C8,4 VG1-C10,9b VG1-C12,4 VG10-C2,13 VG10-C8,13 VG2-
C4,23 SQ01,7 VG2-Br,24 SQ01,7 VG13,13 VG5,15 are known compounds, we compared our samples to the
literature data via NMR spectroscopy.

H
N
O O toluene/BuOH O

N MW, 160°C, 20 min O

HO OH
N
H

SQ-NH

General procedure for symmetrical squaraines synthesis: SQ-NH: 2,3,3-trimethylindolenine (500 mg,
3.14 mmol), 3,4-dihydroxycyclobut-3-ene-1,2-dione (179 mg, 1.57 mmol) and a mixture of toluene and n-
butanol (1:1, 2 mL) were introduced in a microwave vial and heated at 160 °C for 20 min until TLC and UV
showed reaction completion; after solvent evaporation, the crude product was crystallized by n-butanol,
filtered off and washed with diethyl ether to give squaraine SQ-NH as blue crystals (380 mg, yield = 61%)
1
H NMR (CD3OD): δ = 7.42-7.10 (m, 8H), 5.51 (s, 2H), 1.49 (s, 12H)21

21
Borrelli, R.; Ellena, S.; Barolo, C.; Phys. Chem. Chem. Phys. 2014, 16, 2390-2398
22
Moreshead, W. V.; Przhonska, O. V.; Bondar, M. V.; Kachkovski, A. D.; Nayyar, I. H.; Masunov, A. E.; Woodward,
A. W.; Belfield, K. D. J. Phys. Chem. C 2013, 117, 23133-23147
23
Maeda, T.; Mineta, S.; Fujiwara, H.; Nakao, H.; Yagi, S.; Nakazumi, H. J. Mater. Chem. A 2013, 1, 1303-1309
24
Mayerhöffer, U.; Gsänger, M.; Stolte, M.; Fimmel, B.; Würthner, F. Chem.–Eur. J. 2013, 19, 218-232
S12
 Br

Br O O toluene/BuOH O N
H
MW, 160°C, 30 min Br
N O
HO OH
N
H

2a Br-NH

Br-NH: 5-bromo-2,3,3-trimethyl-3H-indole (2a, 238 mg, 1.0 mmol), 3,4-dihydroxycyclobut-3-ene-1,2-

dione (57 mg, 0.5 mmol) and toluene/n-butanol (1:1, 2 mL) were reacted as described in the general
procedure for 30 minutes at 160° C to get Br-NH as dark blue (183 mg, 66 % yield).
1
H NMR (CDCl3): δ = 7.26-7.23 (m, 4H), 7.14-7.03 (m, 2H), 5.52-5.44 (2 s, 2H), 1.44 (s, 12H)
The compound solubility in CDCl3 proved too low to record a 13C NMR spectrum.
HRMS (ESI) calcd for [M+H]+ 555.0106, found 555.0142

N
O O toluene/BuOH O

N MW, 160°C, 15 min O

I HO OH
N

3a R1

R1: 1-Ethyl-2,3,3-trimethyl-3H-indolium iodide (3a, 500 mg, 1.6 mmol), 3,4-dihydroxycyclobut-3-ene-1,2-

dione (90 mg, 0.8 mmol) and toluene/n-butanol (1:1, 2 mL) were reacted as described in the general
procedure for 15 min; solvent evaporation and chromatographic separation (EtOAc/MeOH 95:5) afforded
the pure title compound as blue solid (174 mg, yield = 48%)
1
H NMR (CDCl3): δ = 7.32 (t, J = 7.0 Hz, 4H), 7.12 (t, J = 7.0, 2H), 6.98 (d, J = 8.0 Hz, 2H), 5.95 (bs, 2H),
4.08-4.05 (m, 4H), 1.77 (s, 12H), 1.37 (t, J = 7.0 Hz, 6H)22

N
HOOC O O O
toluene/BuOH COOH
N HOOC
MW, 160°C, 20 min O
I HO OH
N

3b VG1-C2

VG1-C2: 5-carboxy-1-ethyl-2,3,3-trimethyl-3H-indolium iodide (3b, 201 mg, 0.56 mmol), 3,4-

dihydroxycyclobut-3-ene-1,2-dione (32 mg, 0.28 mmol) and toluene/n-butanol (1:1, 1 mL) were reacted as
described in the general procedure for 20 min to get VG1-C2 as dark violet powder (150 mg, yield = 99%)
1
H NMR (DMSO-d6): δ = 8.03 (s, 2H), 7.97 (d, J = 8.0 Hz, 2H), 7.43 (d, J = 8.0 Hz, 2H), 5.89 (s, 2H), 4.19-
4.15 (m, 4H), 1.71 (s, 12H), 1.29 (t, J = 7.0 Hz, 6H)4

N
Br O O toluene/BuOH O
Br
MW, 160°C, 30 min Br
N O
I HO OH
N

3g Br-C2

S13
Br-C2: 5-bromo-2,3,3-trimethyl-1-ethyl-3H-indolium iodide (3g, 394 mg, 1.0 mmol), 3,4-
dihydroxycyclobut-3-ene-1,2-dione (57 mg, 0.5 mmol) and toluene/n-butanol (1:1, 2 mL) were reacted as
described in the general procedure for 30 minutes at 160° C; after solvent evaporation, column
chromatography (CH2Cl2/EtOAc 90/10) afforded Br-C2 as golden-greenish solid (250 mg, 82% yield).
1
H NMR (CDCl3): δ = 7.44 (s, 2H), 7.42 (d, J = 8.0 Hz, 2H), 6.85 (d, J = 8.0 Hz, 2H), 5.93 (s, 2H), 4.04-4.02
(m, 4H), 1.76 (s, 12H), 1.37 (t, J = 7.0 Hz, 6H)
13
C NMR (CDCl3): δ = 182.3, 180.6, 169.2, 144.4, 141.2, 130.9, 125.9, 116.8, 110.6, 86.9, 77.8, 77.2, 76.5,
49.5, 38.7, 27.1, 12.1
HRMS (ESI) calcd for [M+H]+ 611.0732, found 611.0804
C3H7

Br O O toluene/BuOH O
Br
MW, 160°C, 30 min Br
N O
I HO OH
C3H7 N

C3H7

3h Br-C4

Br-C4: 5-bromo-1-butyl-2,3,3-trimethyl-3H-indolium iodide (3h, 422 mg, 1 mmol), 3,4-dihydroxycyclobut-

3-ene-1,2-dione (57 mg, 0.5 mmol) and toluene/n-butanol (1:1, 10 mL) were reacted as described in the
general procedure for 30 min at 160°C; after solvent evaporation, column chromatography (CH2Cl2/EtOAc
90/10) afforded Br-C4 as golden-green solid (230 mg, 69%).
1
H NMR (CDCl3): δ = 7.43 (s, 2H), 7.41 (d, J = 8.0 Hz, 2H), 6.84 (d, J = 8.0 Hz, 2H), 5.95 (s, 2H), 4.17 –
3.75 (m, 4H), 1.80-1.65 (m, 16H), 1.43 (m, 4H), 0.97 (t, J = 7.0 Hz, 6H)
13
C NMR (CDCl3): δ = 182.2, 180.3, 169.6, 144.3, 141.6, 130.8, 125.8, 116.7, 110.8, 87.2, 49.4, 43.8, 29.1,
27.1, 20.4, 14.0
HRMS (ESI) calcd for [M+H]+ 667.1358, found 667.1426
C7H15

N
HOOC O O O
toluene/BuOH COOH
N HOOC
MW, 160°C, 25 min O
I HO OH
C7H15 N

C7H15

3d VG1-C8

VG1-C8: 5-Carboxy-2,3,3-trimethyl-1-octyl-3H-indolium iodide (3d, 3.88 g, 8.76 mmol), 3,4-

dihydroxycyclobut-3-ene-1,2-dione (500 mg 4.38 mmol) and and toluene/n-butanol (1:1, 16 mL) were
reacted as described in the general procedure for 25 min to get VG1-C8 as brown-blue crystals (2.27 g, yield
= 73%)
1
H NMR (DMSO-d6): δ = 12.86 (bs, 2H), 8.04 (s, 2H), 7.97 (d, J = 9.00 Hz, 2H), 7.44 (d, J = 9.00 Hz, 2H),
5.90 (s, 2H), 4.13 (m, 4H), 1.70 (m, 16H), 1.32-1.22 (m, 20H), 0.82-0.79 (m, 6H)4

S14
 C9H19

N
HOOC O O O
toluene/BuOH COOH
N HOOC
MW, 160°C, 20 min O
I HO OH
C9H19 N

C9H19

3e VG1-C10

VG1-C10: 5-carboxy-2,3,3-trimethyl-1-decyl-3H-indolium iodide (3e, 1.00 g, 2.12 mmol), 3,4-

dihydroxycyclobut-3-ene-1,2-dione (120 mg, 1.05 mmol) and toluene/n-butanol (1:1, 8 mL) were reacted as
described in the general procedure for 20 min to get VG1-C10 as blue crystals (506 mg, yield = 63.0%)
1
H NMR (DMSO-d6): δ = 8.08 (s, 2H), 8.00 (d, J = 8.0 Hz, 2H), 7.51 (d, J = 8.0 Hz, 2H), 6.41 (s, 2H), 4.07
(m, 4H), 1.82-1.62 (m, 18H), 1.31-1.21 (m, 28H), 089-0.79 (m, 6H)9b
C11H23

N
HOOC O O O
toluene/BuOH COOH
N HOOC
MW, 160°C, 15 min O
I HO OH
C11H23 N

C11H23

VG1-C12

VG1-C12: 5-carboxy-2,3,3-trimethyl-1-dodecyl-3H-indolium iodide (1.05 g, 2.10 mmol), 3,4-

dihydroxycyclobut-3-ene-1,2-dione (120 mg, 1.05 mmol) and toluene/n-butanol (1:1, 8 mL) were reacted as
described in the general procedure for 15 min to get VG1-C12 as black bluish crystals (242 mg, yield =
28.0%)
1
H NMR (DMSO-d6): δ = 8.02 (s, 2H), 7.96 (d, J = 19.0 Hz, 2H), 7.42 (d, J = 9.0 Hz, 2H), 5.89 (s, 2H), 4.12
(m, 4H), 1.70 (s, 16H), 1.39-1.20 (m, 36 H), 0.86 (t, J = 7.0 Hz, 3H)4
HRMS (ESI) calcd for [M+H]+ 821.5390, found 821.5371

C11H23

Br O O toluene/BuOH O
Br
MW, 160°C, 30 min Br
N O
I HO OH
C11H23 N

C11H23

3i Br-C12

Br-C12: 5-bromo-1-dodecyl-2,3,3-trimethyl-3H-indolium iodide (3i, 962 mg, 1.8 mmol), 3,4-

dihydroxycyclobut-3-ene-1,2-dione (103 mg, 0.9 mmol) and toluene/n-butanol (1:1, 18 mL) were reacted as
described in the general procedure for 30 min at 160°C; after solvent evaporation, column chromatography
(CH2Cl2/EtOAc 90/10) afforded Br-C12 as brown reddish crystals (321 mg, yield = 72%).
1
H NMR (CDCl3): δ = 7.41 (s, 2H), 7.37 (d, J = 8.0 Hz, 2H), 6.81 (d, J = 8.0 Hz, 2H), 5.91 (s, 2H), 3.91 (m,
4H), 1.74 (m, 16H), 1.30-1.21 (m, 36H), 0.82 (t, J = 6.0 Hz, 6H)
13
C NMR (CDCl3): δ = 182.1, 180.3, 169.4, 144.2, 141.6, 130.7, 125.7, 116.6, 110.7, 87.1, 49.4, 43.9, 31.9,
29.6, 29.5, 29.5, 29.3, 27.1, 22.7, 14.2
HRMS (ESI) calcd for [M+H]+ 891.3862, found 891.3862

S15
 N
HOOC O O toluene/BuOH O
COOH
N HOOC
MW, 160°C, 20 min O
I HO OH
N

3f VG1-H6

VG1-H6: 5-carboxy-1-(hex-5-ynyl)-2,3,3-trimethyl-3H-indolium iodide (3f, 979 mg, 2.38 mmol), 3,4-

dihydroxycyclobut-3-ene-1,2-dione (130 mg, 1.14 mmol) and toluene/n-butanol (1:1, 18 mL) were reacted as
described in the general procedure for 20 min, yielding VG1-H6 as dark blue crystals (500 mg, yield =
68%).
HRMS (ESI) calcd for [M+H]+ 645.2965, found 645.3079; [M+Na]+: 667.2919
1
H NMR (DMSO-d6): δ = 12.8 (bs, 2H), 8.04 (s, 2H), 7.97 (d, J = 8.0 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H), 5.92
(s, 2H), 4.16 (m, 4H), 2.80 (t, J = 3.0 Hz, 2H), 2.25 (t, J = 6.0 Hz, 4H), 1.90-1.75 (m, 4H), 1.71 (s, 12H),
1.65-1.48 (m, 4H)
13
C NMR (DMSO-d6): δ 180.8, 170.1, 167.3, 146.1, 141.8, 130.5, 126.2, 123.4, 110.5, 87.9, 84.3, 71.9, 48.8,
26.7, 26.1, 25.5, 17.7
UV-Vis (Abs in MeOH): 643 nm

HOOC N
O O toluene/BuOH HOOC O

N MW, 160°C, 40 min O COOH

I HO OH
N

5a VG10-C2

VG10-C2: 7-carboxy-3-ethyl-1,1,2-trimethyl-1H-benzo[e]indol-3-ium iodide (5a, 205 mg, 0.5 mmol), 3,4-

dihydroxycyclobut-3-ene-1,2-dione (29 mg, 0.25 mmol) and toluene/n-butanol (1:1, 5 mL) were reacted as
described in the general procedure for 40 min to obtain VG10-C2 as dark green solid (144 mg , yield = 90%)
1
H NMR (DMSO-d6): δ = 8.68 (s, 2H), 8.34-8.22 (m, 4H), 8.07 (d, J = 9.0 Hz, 2H), 7.80 (d, J = 9.0 Hz, 2H),
5.92 (s, 2H), 4.31 (m, 4H), 1.97 (s, 12H), 1.35 (t, J = 7.0 Hz, 6H)13
C7H15

HOOC N
O O toluene/BuOH HOOC O

N MW, 160°C, 40 min O COOH

I HO OH
C7H15 N

C7H15

5b VG10-C8

VG10-C8: 7-carboxy-1,1,2-trimethyl-3-octyl-1H-benzo[e]indol-3-ium iodide (5b, 197 mg, 0.4 mmol), 3,4-

dihydroxycyclobut-3-ene-1,2-dione (23 mg, 0.4 mmol) and toluene/n-butanol (1:1, 5 mL) were reacted as
described in the general procedure for 40 min to obtain VG10-C8 as light blue solid (102 mg , yield = 63%)

S16
1
H NMR (DMSO-d6): δ = 8.66 (s, 2H), 8.32-8.18 (m, 4H), 8.08 (d, J = 9.0 Hz, 2H), 7.75 (d, J = 9.0 Hz, 2H),
5.96 (s, 2H), 4.26 (m, 4H), 2.00 (s, 12H), 1.81 (m, 4H), 1.38-1.25 (m, 10H), 0.84 (m, 6H)13

4-(dimethylamino)pyridin-1-ium 3-(dicyanomethylene)-2-ethoxy-4-oxocyclobut-1-enolate (8): diethyl

squarate (0.7 ml, 4.6 mmol), malononitrile (304 mg, 4.6 mmol), 4-(dimethylamino)pyridine (562 mg, 4.6
mmol) and 10 ml of toluene were introduced in a round bottom flask and stirred at room temperature for 30
min; the precipitate was filtered to obtain 8 as yellow solid (1.25 g, yield = 87%)25
1
H NMR (DMSO-d6): δ = 8.21 (d, J = 8.0 Hz, 2H), 6.98 (d, J = 8.0 Hz, 2H), 4.62 (q, J = 7.0, 2H), 3.18 (s,
6H), 1.34 (t, J=7.0, 3H)
13
C NMR (DMSO-d6): δ = 191.3, 180.8, 179.9, 172.4, 156.9, 139.1, 117.9, 117.6, 106.9, 68.4, 39.6, 15.7
HRMS (ESI) calcd for [M]- 189.0300, found 189.0348

NC CN

NC
H
HOOC O CN N C3H7 C3H7
toluene/BuOH N N
N O
I MW, 160°C, 30 min
O O N
C3H7

COOH COOH

3c 8 VG2-C4

VG2-C4: 5-Carboxy-1-butyl-2,3,3-trimethyl-3H-indolium iodide (3c, 200 mg, 0.52 mmol), 4-

(dimethylamino)pyridin-1-ium 4-(dicyanomethylene)-2-ethoxy-3-oxocyclobut-1-enolate (8, 81 mg, 0.26
mmol) and toluene/n-butanol (1:1, 1 mL) were reacted as described in the general procedure for 30 min to
obtain VG2-C4 as dark green powder (34 mg , yield = 20%)23
HRMS (ESI) calcd for [M+H]+ 645.2999, found 645.3018

NC CN

NC
H
Br O CN N toluene/BuOH N N
N O
I MW, 160°C, 30 min
O O N

Br Br

3g 8 VG2-Br

VG2-Br: 5-bromo-1-ethyl-2,3,3-trimethyl-3H-indolium iodide (3g, 473 mg, 1.2 mmol), 4-

(dimethylamino)pyridin-1-ium 4-(dicyanomethylene)-2-ethoxy-3-oxocyclobut-1-enolate (8, 187 mg, 0.6
mmol) and toluene/n-butanol (1:1, 18 mL) were reacted as described in the general procedure for 30 min; the
reaction mixture was extracted with dichloromethane/H2O, and the organic phase was dried and evaporated;
column chromatography (dichloromethane:EtOAc = 95:5) afforded VG2-Br as a green-golden powder (122
mg, yield = 31%)
1
H NMR (CDCl3): δ = 7.58 (s, 2H), 7.07 (d, J = 8.6 Hz, 2H), 6.63 (s, 2H), 6.51 (d, J = 8.6 Hz, 2H), 3.64 (q, J
= 6.0 Hz, 1H), 1.89 (s, 12H), 1.27 (t, J= 6.0 Hz, 6H)24
HRMS (ESI) calcd for [M+H]+ 659.0766, found 659.0777

25
Zubatyuk, R. I.; Baumer, V. N.; Tatarets, A. L.; Patsenker, L. D.; Shishkin, O. V. Acta Crystallogr. Sect. A 2004 E60,
o2252-o2254
S17
2-((2-Ethoxy-3,4-dioxocyclobut-1-enyl)methylene)- 3,3-dimethyl-1-ethylindolenine-5-carboxylic acid
(6a): 5-Carboxy-2,3,3-trimethyl-1-ethyl-3H-indolium iodide (3b, 431 mg, 1.2 mmol) and 3,4-diethoxy-3-
cyclobutene-1,2-dione (0.2 mL, 1.2 mmol) were refluxed in a triethylamine/ethanol (0.7/10 ml) mixture for
15 min; after diethyl ether addition and cooling in fridge, a solid was obtained, which was filtered and
purified by column chromatography (CHCl3/MeOH = 97/3) to afford the title product as brown powder (375
mg, yield = 88%)
1
H-NMR (DMSO-d6): δ = 12.65 (bs, 1H), 7.93 (s, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.22 (d, J = 8.0 Hz, 1H),
5.43 (s, 1H), 4.83 (q, J = 7.0 Hz, 2H), 3.97 (q, J = 8.0 Hz, 2H), 1.56 (s, 6H), 1.45 (t, J = 7.0 Hz, 3H), 1.21 (t,
J = 8.0 Hz, 3H)
13
C NMR (DMSO-d6):  = 191.8, 188.9, 187.2, 172.6, 167.1, 166.7, 145.8, 140.4, 130.4, 124.5, 122.9, 108.4,
82.0, 70.0, 46.9, 37.3, 26.4, 15.6, 11.0
HRMS (ESI) calcd for [M+H]+ 356.1498, found 356.1562, [M+Na]+: 378.1384, [2xM]+: 733.2880

2-((2-Ethoxy-3,4-dioxocyclobut-1-enyl)methylene)-3,3-dimethyl-1-octylindolenine-5-carboxylic acid
(6b): 5-Carboxy-2,3,3-trimethyl-1-octyl-3H-indolium iodide (3d, 0.49 g, 1.1 mmol), 3,4-diethoxy-3-
cyclobutene-1,2-dione (0.3 mL, 2.2 mmol) and a mixture triethylamine/EtOH (0.4/10 ml) were introduced in
a reaction vial, which was sealed and heated in the microwave system at 90 °C for 45 min; after diethyl ether
addition and cooling in fridge, a solid was obtained, which was filtered and purified by column
chromatography (CHCl3/MeOH = 97/3) to give the title compound as brown yellowish solid (0.43 g, yield =
88%)
1
H-NMR (DMSO-d6): δ = 12.70 (bs, 1H), 7.92 (s, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.22 (d, J = 8.0 Hz, 1H),
5.43 (s, 1H), 4.82 (q, J = 7.5 Hz, 2H), 3.91 (m, 2H), 1.67-1.64 (m, 2H), 1.56 (s, 6H), 1.44 (t, J = 7.5 Hz, 3H),
1.29-1.21 (m, 10 H), 0.83 (m, 3H)14

1-Decyl-2-((2-ethoxy-3,4-dioxocyclobut-1-enyl)methylene)-3,3-dimethylindolenine-5-carboxylic acid
(6c): 5-Carboxy-2,3,3-trimethyl-1-decyl-3H-indolium iodide (3e, 1.98 g, 4.2 mmol), 3,4-diethoxy-3-
cyclobutene-1,2-dione (1.2 mL, 8.4 mmol) and a mixture triethylamine/EtOH (1.1/14 ml) were introduced in
a reaction vial, which was sealed and heated in the microwave system at 100 °C for 45 min; after diethyl
ether addition and cooling in fridge, a solid was obtained, which was filtered and purified by column
chromatography (CHCl3/MeOH = 97/3) to give the title compound as red-orange crystals (1.47 g, yield =
75%)
1
H-NMR (DMSO-d6): δ = 12.70 (bs, 1H), 7.92 (s, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.23 (d, J = 8.0 Hz, 1H),
5.43 (s, 1H), 4.82 (q, J = 7.0 Hz, 2H), 3.92 (t, J = 7.0 Hz, 2H), 1.64 (m, 2H), 1.56 (s, 6H), 1.44 (t, J = 7.0 Hz,
3H), 1.34-1.20 (m, 14 H), 0.82 (t, J = 7.0 Hz, 3H)
13
C NMR (DMSO-d6): δ = 191.8, 188.9, 187.2, 172.5, 167.1, 167.1, 146.4, 140.2, 130.3, 124.5, 124.1, 122.9,
108.7, 82.4, 70.0, 46.9, 31.3, 29.0, 28.8, 28.6, 28.5, 26.5, 26. 0, 25.7, 22.1, 15.6, 13.9
HRMS (ESI) calcd for [C28H38NO5]+ [M+H]+ 468.2744, found 468.2823

2-((2-ethoxy-3,4-dioxocyclobut-1-enyl)methylene)-1,1-dimethyl-3-octyl-2,3-dihydro-1H-benzo[e]indole-
7-carboxylic acid (7): 7-carboxy-1,1,2-trimethyl-3-octyl-1H-benzo[e]indoleninium (5b, 493 mg, 1.0 mmol),
3,4-diethoxycyclobut-3-ene-1,2-dione (0.3 mL, 2.0 mmol), EtOH (10 mL) and triethylamine (0.4 mL, 3.0
mmol) were added to a MW vial, which was closed with a crimp cap and heated at 90 °C for 50 min; after
evaporation, column chromatography (CH2Cl2/MeOH 9/1) afforded the pure title compound as dark yellow
powder (240 mg, 49% yield)13
1
H-NMR (CD3OD): δ = 8.58 (s, 1H), 8.05 (s, 2H), 7.90 (d, J = 8.0 Hz, 1H), 7.26-7.20 (m, 1H), 5.44 (s, 1H),
4.87 (q, J = 7.0 Hz, 2H), 3.88 (t, J = 7.0 Hz, 2H), 1.83 (s, 6H), 1.74 (m, 2H), 1.51 (t, J = 7.0 Hz, 3H), 1.35-
1.19 (m, 10H), 0.61 (m, 3H)

S18
 O N
O
toluene/BuOH O
HOOC O
MW, 160°C, 25 min HOOC
N O
N I
N
C7H15
C7H15

6b 3a SQ01

General procedure for unsymmetrical squaraines synthesis: SQ01: 2-((2-Ethoxy-3,4-dioxocyclobut-1-

enyl)methylene)-3,3-dimethyl-1-octylindolenine-5-carboxylic acid (6b, 176 mg, 0.4 mmol), 1-ethyl-2,3,3-
trimethyl-3H-indolium iodide (3a, 126 mg, 0.4 mmol) and a mixture of toluene and n-butanol (1:1, 8 mL)
were introduced in a microwave vial and heated at 160 °C for 25 min; the solvent was removed by
distillation and the crude product was crystallized by n-butanol, filtered off and washed with diethyl ether to
get squaraine SQ01 as dark reddish crystals with golden sparkles (160 mg, yield = 69%)
1
H NMR (DMSO-d6): δ = 12.80 (bs, 1H), 7.98 (s, 1H), 7.93 (d, J = 7.0 Hz, 1H), 7.58 (d, J = 7.0 Hz, 1H),
7.42-7.31 (m, 3H), 7.23 (t, J = 7.0 Hz, 1H), 5.88 (s, 1H), 5.80 (s, 1H), 4.21-4.18 (m, 2H), 4.05 (m, 2H), 1.69
(s, 14H), 1.34-1.22 (m, 13H), 0.82-0.79 (m, 3H)7

O N
O
HOOC toluene/BuOH O
HOOC O COOH
N MW, 160°C, 25 min HOOC
O
N I
N

6a 3f VG1-C2-H6

VG1-C2-H6: 2-((2-ethoxy-3,4-dioxocyclobut-1-enyl)methylene)-1-ethyl-3,3-dimethylindoline-5-carboxylic
acid (6a, 213 mg, 0.6 mmol), 5-carboxy-1-(hex-5-ynyl)-2,3,3-trimethyl-3H-indol-1-ium iodide (3f, 247 mg,
0.6 mmol) and toluene/n-butanol (1:1, 10 mL) were reacted as described in the general procedure for 25 min
to obtain VG1-C2-H6 as dark blue powder (128 mg, yield = 36%).
1
H-NMR (DMSO-d6): δ = 12.84 (bs, 2H), 8.04 (s, 2H), 7.97 (d, J = 8.0 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H),
5.92-5.89 (2 s, 2H), 4.16 (m, 4H), 2.80 (m, 1H), 2.25 (t, J = 7.0 Hz, 2H), 1.71-1.57 (m, 14H), 1.39-1.30 (m,
5H)
13
C-NMR (DMSO-d6): δ = 180.8, 180.5, 169.6, 169.5, 167.0, 145.9, 145.4, 141.7, 130.3, 125.9, 125.8, 123.2,
110.1, 110.0, 87.6, 87.2, 84.0, 71.7, 60.4, 48.6, 48.6, 48.5, 34.7, 26.5, 26.4, 25.8, 25.2, 18.6, 17.4, 13.9, 11.8
UV-Vis (Abs in MeOH): 643 nm
HRMS (ESI) calcd for [M+H]+ 593.2652, found 593.2737

S19
 O N
O
HOOC toluene/BuOH O
HOOC O COOH
N MW, 160°C, 25 min HOOC
O
N I
N
C7H15
C7H15

6b 3f VG1-C8-H6
VG1-C8-H6: 2-((2-ethoxy-3,4-dioxocyclobut-1-enyl)methylene)-3,3-dimethyl-1-octylindoline-5-carboxylic
acid (6b, 132 mg, 0.3 mmol), 5-carboxy-1-(hex-5-ynyl)-2,3,3-trimethyl-3H-indol-1-ium iodide (3f, 123 mg,
0.3 mmol) and toluene/n-butanol (1:1, 5 mL) were reacted as described in the general procedure for 25 min
yielding VG1-C8-H6 as blue solid (124 mg, yield = 61%).
1
H-NMR (DMSO-d6): δ = 8.03 (s, 2H), 7.97 (d, J = 10.0 Hz, 2H), 7.45-7.40 (m, 2H), 5.91-5.90 (2 s, 2H),
4.15 (m, 4H), 2.81 (t, J = 3.0 Hz, 1H), 2.25 (t, J = 7.0, 2H), 1.71-1.56 (m, 18H), 1.33- 1.23 (m, 10H), 0.83 (t,
J = 7.0, 3H)
13
C NMR (DMSO-d6): δ = 180.6, 169.9, 167.1, 145.9, 141.5, 130.3, 126.0, 123.2, 110.2, 87.6, 84.0, 71.8,
48.6, 48.5, 31.1, 28.6, 28.6, 26.5, 26.2, 25.8, 25.2, 22.0, 17.4, 13.9, 13.6
UV-Vis (Abs in MeOH): 643 nm
HRMS (ESI) calcd for [M+H]+ 677.3591, found 677.3702

O N
O
HOOC toluene/BuOH O
HOOC O COOH
N MW, 160°C, 25 min HOOC
O
N I
N
C9H19
C9H19

6c 3f VG1-C10-H6

VG1-C10-H6: 1-decyl-2-((2-ethoxy-3,4-dioxocyclobut-1-enyl)methylene)-3,3-dimethylindoline-5-
carboxylic acid (6c, 281 mg, 0.6 mmol), 5-carboxy-1-(hex-5-ynyl)-2,3,3-trimethyl-3H-indolium iodide (3f,
247 mg, 0.6 mmol) and toluene/n-butanol (1:1, 10 mL) were reacted as described in the general procedure
for 35 min to obtain VG1-C10-H6 as blue-brownish solid (220 mg, yield = 52%).
1
H-NMR (DMSO-d6): δ 12.86 (bs, 2COOH), 8.03 (s, 2H), 7.87 (d, J = 10.0 Hz, 2H), 7.46-7.40 (m, 2H),
5.92-5.91 (m, 2H), 4.16 (m, 4H), 2.79 (t, J = 2.0 Hz, 1H), 2.24 (t, J = 7.0 Hz, 2H), 1.71 (s, 12H), 1.61-1.56
(m, 4H), 1.31 (m, 4H), 1.20 (m, 12H), 0.82 (t, J = 6.0 Hz, 3H)
13
C NMR (DMSO-d6): δ 180.7, 180.4, 169.9, 169.6, 167.0, 145.9, 141.5, 130.2, 125.9, 125.9, 123.2, 110.2,
87.6, 83.9, 71.6, 48.5, 48.5, 31.2, 28.8, 28.7, 28.6, 26.4, 26.0, 25.7, 25.2, 22.0, 17.4, 16.3, 13.9
UV-Vis (Abs in MeOH): 643 nm
HRMS (ESI) calcd for [M+H]+ 705.3904, found 705.4027

S20
 N
HOOC O O
HOOC O
toluene/BuOH
O
N O
N I MW, 160°C, 35 min
N
C7H15
C7H15

7 VG13

VG13: 2-((2-ethoxy-3,4-dioxocyclobut-1-enyl)methylene)-1,1-dimethyl-3-octyl-2,3-
dihydro-1H-benz[e]indole-7-carboxylic acid (7, 147 mg, 0.3 mmol), 3-ethyl-1,1,2-trimethyl-1H-
benz[e]indoleninium iodide (110 mg, 0.3 mmol) and toluene/n-butanol (1:1, 6 mL) were reacted as described
in the general procedure for 35 min to get VG13 as a dark blue solid (108 mg, yield = 53%)
1
H-NMR (DMSO-d6): δ = 8.66 (s, 1H), 8.32-8.18 (m, 3H), 8.07-8.02 (m, 3H), 7.75 (d, J = 6.0 Hz, 2H), 7.64
(t, J = 7.0 Hz, 1H), 7.50-7.47 (t, J = 7.0 Hz, 1H), 5.91 (bs, 2H), 4.30 (m, 4H), 1.96 (s, 12H), 1.76 (m, 2H),
1.39-1.23 (m, 13H), 0.86 (t, 8.0 Hz, 3H)13
O O C7H15
HOOC
toluene/BuOH N
O O
N
N MW, 160°C, 60 min
ClO4
HOOC O
C7H15 N

6b VG5

VG5: 2-((2-Ethoxy-3,4-dioxocyclobut-1-enyl)methylene)-3,3-dimethyl-1-octylindolenine-5-carboxylic acid

(296 mg, 1.0 mmol), 1-Ethyl-2-methylbenz[cd]indolium perchlorate (440 mg, 1.0 mmol) and toluene/n-
butanol (1:1, 6 mL) were reacted as described in the general procedure for 60 min; the product was purified
by flash chromatography (CHCl3/CH3OH = 9:1) affording VG5 as dark green solid (88 mg, yield = 15%)
1
H-NMR (DMSO-d6): δ = 9.14 (bs, 1H), 8.13-8.00 (m, 2H), 7.92 (d, J = 8.0 Hz, 1H), 7.81 (t, J = 7.0 Hz, 1H),
7.56-7.42 (m, 2H), 7.02 (t, J = 6.0 Hz, 2H), 6.33 (s, 1H), 6.10 (s, 1H), 4.22 (m, 2H), 4.09-4.05 (m, 2H), 1.84
(m, 8H), 1.54-1.24 (m, 10H), 0.99 (t, 8.0 Hz, 3H), 0.85-0.82 (m, 3H)15

S21
Comments on the reproducibility of MW reactions

Microwave reactions yields reported in the manuscript are the mean results of a number of experiments
(usually more than three for each entry).

Modern microwave reactors such as the Biotage Initiator provide a very accurate monitoring system of
temperature and pressure, which leads to highly reproducible reaction conditions and yields.26 For instance,
in the quaternization of 5-carboxy-2,3,3-trimethyl indolenine with 1-iodooctane, three repetitions in the same
conditions afforded an average yield of 60.33% with a 1.15% standard deviation (Table S1, entries 9-11),
and similarly with 1-iododecane (average yield of 59% with 1% standard deviation). In classical conditions,
the yield was 44.4% ± 9.7 (5 repetitions) for 1-iodooctane.

The yield distribution per entry in the case of microwave reactions was not reported in the tables, due to lack
of space and for sake of clarity, since the maximum standard deviation was lower than 5% in the less
favorable cases.

26
Kappe, C. O. Angew. Chem. Int. Ed. 2004, 43, 6250–6284
S22
1
H NMR spectrum of 3a

S23
1
H NMR spectrum of 3b

S24
1
H NMR spectrum of 3c

S25
1
H NMR spectrum of 3d

S26
1
H NMR spectrum of 3e

S27
 1
199.67

166.45

144.29
142.28
H and 13C NMR spectra of 3f

1.12 8.38
2.00 8.16
131.66
130.43

124.42

115.71

83.93

1.96 4.53

71.82

2.92
54.56
2.70 2.82
1.27 2.52
47.56 2.51
2.50
2.49
40.77
38.27 2.25 2.48
2.13 2.26
8.72 2.23
2.07
1.93
26.33 1.59
24.85
21.91
17.38
14.77

-0.03

-0.98

S28
1
H NMR spectrum of 3g

Br-indolenina C2 DMSO

1.55
1.46
1.42
1.39
Br

+
N -
I

2.83
2.51
2.50
2.49
8.19
7.97
7.93
7.87
7.83

4.54
4.50
4.46
4.43
1.00
1.05
0.94

1.93

2.92

5.81
3.05
12.5 11.5 10.5 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5
f1 (ppm)

S29
1
H NMR spectrum of 3h

Br indolenina C4 DMSO 1H

1.87
1.83
1.80
1.76
1.72
1.55
1.47
1.44
1.40
1.36
Br

+
N
-
I

2.85

2.50

0.96
0.92
0.89
8.20
7.99
7.95
7.86
7.81

4.48
4.45
4.41
1.00
1.06
1.09

1.92

2.85

2.16
5.93
2.46

3.07
13.5 12.5 11.5 10.5 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5
f1 (ppm)

S30
1
H NMR spectrum of 3i

S31
1H NMR spectrum of 5a

S32
1
H NMR spectrum of 5b

S33
1
H NMR spectrum of SQ-NH

S34
1
H NMR spectrum of Br-NH

S35
1
H NMR spectrum of R1

S36
1
H NMR spectrum of VG1-C2

S37
1
H and 13C NMR spectra of Br-C2

Br-C2 CDCl3 13C

27.11

Br +
O N
49.52

-
N O
Br
116.77

110.57

12.05
130.87
125.91
169.23
182.30
180.56

144.39
141.16

38.70
86.89

210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)

S38
1
H and 13C NMR spectra of Br-C4

diBrSQ_C4 CDCl3 1H

1.76
1.53
1.49
1.45
1.41
1.38
1.34
1.01
0.97
0.94
Br -
O N

+
N O
Br

7.43
7.39
7.26

5.95
6.86
6.82

3.98
3.95
3.92
2.08

0.99

1.00

2.06

8.39
2.69

3.33
13.5 12.5 11.5 10.5 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5
f1 (ppm)

diBrSQ_C4 CDCl3 13C

29.10
27.14

Br -
O N

+
N O
Br
13.95
49.44

43.75
116.68

110.79

20.44
130.77
125.80
169.56

144.28
141.63

87.16
182.24
180.32

210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 -10
f1 (ppm)

S39
1
H NMR spectrum of VG1-C8

S40
 1
12.96
1.31

H NMR spectrum of VG1-C10

8.08
2.00
8.02
2.12
7.98
7.53
1.86
7.49

1.64 6.41

4.74 4.07

3.35

2.60
2.51
2.50
2.40
1.82
23.24 1.72
1.62
1.31
32.52 1.21
0.89
0.85
12.84 0.82
0.79

S41
 1

182.11
180.29

169.40
H NMR spectra of Br-C12

144.22
141.56

130.69

125.70

116.59

110.72

87.11

77.80
77.16
76.52

49.35

43.89

31.91
29.59
29.51
29.46
29.33
27.06
22.70
14.16

S42
1
H and 13C NMR spectra of VG1-H6

S43
1
H NMR spectrum of VG10-C2

mb 2-9 bis 1000

H3C

900

O N

- 800
O
HO H3 C
CH3 H3 C
CH3 OH
O
700

+
N O

600

CH3

500

400

300

200

100

12.5 11.5 10.5 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
f1 (ppm)

S44
1
H NMR spectrum of VG10-C8

S45
1
H and 13C NMR spectra of 8

S46
1
H and 13C NMR spectra of 6a

S47
1
H NMR spectrum of 6b

COOHemisquarato_C8 DMSO 1H 850

1.67
1.64
1.56
1.47
1.44
1.40
1.29
1.21
O
H3 C
CH3 800

HO
750
O
N 700

650
O O

600
H3C
550

500
H3 C
450

400

350

300

0.82
0.79
7.92
7.88

250

200
5.43

4.87
4.83
4.80
4.76

2.50
150

3.91
7.24
7.20

100

3.34
12.70

50

11.31
-50
0.47

2.00

1.03

0.95

1.97

1.98

2.11
5.83
3.99

3.75
12.5 11.5 10.5 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0
f1 (ppm)

S48
1
H and 13C NMR spectra of 6c

S49
1
H NMR spectrum of 7

S50
1
H NMR spectrum of SQ01

S51
 1
1.61 12.84

180.79
180.49

169.62
169.50
167.04

145.91
145.37
141.67

8.04
4.00 7.99
130.28 7.95
125.93
125.84 7.46
2.09
123.22 7.42
H and 13C NMR spectra of VG1-C2-H6

110.14
109.98

1.75 5.92
5.89

87.56
87.16
83.99

4.61 4.16
71.71

3.41
60.36 3.38
3.35
2.80
48.60 1.08 2.79
48.55 2.51
48.52 2.50
40.77 2.29
40.20 3.06
2.25
39.78 2.22 1.71
38.27 14.73 1.61
34.68 1.57
26.47
26.35 1.39
4.93 1.33
25.77
25.20 0.89 1.30
18.63 0.86
17.43 0.82
13.85
11.76

S52
1
H and 13C NMR spectra of VG1-C8-H6

S53
1
H and 13C NMR spectra of VG1-C10-H6

S54
1
H NMR spectrum of VG13

S55
1
H NMR spectrum of VG5

S56