Diversity-oriented synthesis of azo disperse dyes with improved fastness properties via employing Ugi four-component reaction

Article abstract of DOI:10.1016/j.dyepig.2019.02.039

A novel approach has been established for accessing structurally diverse azo disperse dyes with improved fastness properties by employing an Ugi four-component reaction (Ugi-4CR). The process includes three steps: (1) Ugi-4CR of aniline, cyclohexyl isocyanide, formic acid, and an aromatic aldehyde; (2) selective hydrolysis of amide functionality in the Ugi product; and (3) coupling the hydrolysis product with an aryl diazonium salt. Employing Ugi-4CR herein had advantages over easily controlling the molecular weight/size of the dye. Six new azo disperse dyes were synthesized and their structures were fully characterized by ¹H NMR, ¹³C NMR, MS, and FT-IR. It was found that the washing and sublimation fastness properties of the obtained azo disperse dyes on both poly (ethylene terephthalate) (PET) and nylon fibers were remarkably improved as compared with conventional C.I. Disperse Orange 3. The improved fastness properties should be attributed to the moderately increased molecular weight/size and the amide functionality introduced in Ugi-4CR.

Full text of DOI:10.1016/j.dyepig.2019.02.039

Accepted Manuscript
Diversity-oriented synthesis of azo disperse dyes with improved fastness properties
via employing Ugi four-component reaction
Huanhuan Li, Hong-Fei Qian, Gaofeng Feng
PII:
S0143-7208(18)32720-7
https://doi.org/10.1016/j.dyepig.2019.02.039
DYPI 7373
DOI:
Reference:
To appear in: Dyes and Pigments
Received Date: 18 December 2018
Revised Date: 18 February 2019
Accepted Date: 23 February 2019
Please cite this article as: Li H, Qian H-F, Feng G, Diversity-oriented synthesis of azo disperse dyes with
improved fastness properties via employing Ugi four-component reaction, Dyes and Pigments (2019),
doi: https://doi.org/10.1016/j.dyepig.2019.02.039.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
Graphical Abstract：

ACCEPTED MANUSCRIPT
Diversity-Oriented Synthesis of Azo Disperse Dyes with Improved
Fastness Properties via Employing Ugi Four-component Reaction
Huanhuan Li, Hong-Fei Qian, and Gaofeng Feng*
Zhejiang Key Laboratory of Alternative Technologies for Fine Chemicals Process,
Shaoxing University, Shaoxing, 312000, People’s Republic of China.
*Corresponding author. Tel: +86-575-88345682; E-mail address: chfeng@usx.edu.cn
Abstract: A novel approach has been established for accessing structurally diverse
azo disperse dyes with improved fastness properties by employing an Ugi
four-component reaction (Ugi-4CR). The process includes three steps: (1) Ugi-4CR of
aniline, cyclohexyl isocyanide, formic acid, and an aromatic aldehyde; (2) selective
hydrolysis of amide functionality in the Ugi product; and (3) coupling the hydrolysis
product with an aryl diazonium salt. Employing Ugi four-component reaction herein
had advantages over easily controlling the molecular weight/size of the dye. Six new
azo disperse dyes were synthesized and their structures were fully characterized by 1H
NMR, 13C NMR, MS, and FT-IR. It was found that the washing and sublimation
fastness properties of the obtained azo disperse dyes on both poly(ethylene
terephthalate) (PET) and nylon fibers were remarkably improved as compared with
conventional C.I. Disperse Orange 3. The improved fastness properties should be
attributed to the moderately increased molecular weight/size and the amide
functionality introduced in Ugi-4CR.
Keywords: diversity-oriented synthesis; azo disperse dye; Ugi four-component
reaction; fastness properties
1. Introduction
Disperse dyes are one of the most important dye categories and of great
significance in textile industry [1-4]. Among disperse dyes, azo disperse dyes have
attracted particular attention and they have been widely applied for dyeing natural and

ACCEPTED MANUSCRIPT
synthetic fibers [5,6]. Synthetically, azo disperse dyes are easily prepared through
coupling electron-poor diazonium salts with electron-rich aromatics to form a
Donor-π-Acceptor system. A broad range of colors could be readily obtained by
tuning the electronic properties of substituents on both coupling partners. Recently,
with the development of new fibers, the existing azo disperse dyes show some relative
drawbacks in color fastness. Thus, developing new synthetic approaches to rapidly
access structurally diverse azo disperse dyes with good to excellent dyeing properties
is highly desirable.
It has been demonstrated that increasing the interaction between fiber and disperse
dye reduces dye migration, leading to improved dyeing properties [7,8]. Generally,
there are two ways to minimize the degree of migration and improve dye fastness
properties: one is the moderate increase of the disperse dye molecular weight/size. As
the weight/size of disperse dye becomes larger, the van der Waals force between
disperse dye and fiber becomes stronger once a disperse dye penetrates into the fiber
[9-13]. The other is introducing special functional groups, such as ester, amide, and
urethane that can form hydrogen bonding with fibers. Therefore, to design disperse
dyes with good dyeing properties, a moderate increase of molecular weight/size along
with introducing functional groups that can form hydrogen-bonding interactions with
fibers are two generally useful principles.
Diversity-oriented synthesis [14-16] (DOS) has emerged as a powerful approach to
access a library of skeletally and stereochemically diverse small molecules for
discovering prospective drug candidates through high-throughput screening.
Multicomponent reactions [17,18] (MCRs) assemble three or more reactants in a
highly atom-economic manner and provide an excellent platform for efficient
generation of molecules with diversity and complexity through changing one of the
reactants or post-manipulations of the resulting products[19-21]. Ugi four-component
reaction (Ugi-4CR)[22], the condensation of an aldehyde, an amine, an isocyanide,
and a carboxylic acid for rapid providing α-aminoacyl amide derivatives 1 (Scheme 1),
features with mild reaction conditions, 100% atom economy, and easy generation of
structural diversity. It has been widely applied in diversity-oriented synthesis of

ACCEPTED MANUSCRIPT
heterocycles [23], drug candidates [24], natural products [25,26], polymers [27-29],
and so on. However, it has not been yet reported, to the best of our knowledge, in the
synthesis and application of disperse dyes.
We envisaged that a Ugi product 1 is an ideal azo coupling partner (R4 = Ph) to be
coupled with an aryl diazonium salt 2 for the synthesis of structurally diverse azo
disperse dyes with controlled molecular weight/size and good fastness properties
(Scheme 1). The azo disperse dyes obtained through this method have several
advantages: (1) the structure diversity and the controlling molecular weight/size of
dye could be easily achieved by changing one or more of the four inputs; (2) the
amide subunit introduced in Ugi-4CR can form hydrogen-bonding interactions with
fibers and it is good for improving fastness properties. Connecting our ongoing
research on developing novel disperse dyes [7,8], we report herein diversity-oriented
synthesis of azo disperse dyes with controlled molecular weight/size and improved
fastness properties by employing an Ugi-4CR.
Scheme 1. Ugi four-component reaction and it’s application in azo disperse dye
synthesis.

ACCEPTED MANUSCRIPT
2. Experimental
2.1. General
C.I. Disperse Orange 3 was provided by Zhejiang Longsheng Chemical Co., Ltd
(China) and purified by repeated recrystallization in acetone before use. The structure
is illustrated in Fig. 1.
Dispersing agent sodium salt of polycondensated naphthalenesulfonic acid [MF]
was obtained from Zhejiang Longsheng Co., Ltd (China). Acetone,
N,N-dimethylformamide, sodium hydroxide, ammonium sulfate and sodium dithionite
were purchased from Aladdin industrial corporation and used as received. In addition,
other chemical reagents used in the synthesis and characterization were laboratory
reagent grades.
1H NMR and 13C NMR spectra were recorded on Brucker AVANCE 400MHz
spectrometer (400 MHz for 1H NMR and 100 MHz for 13C NMR, respectively). NMR
chemical shifts are expressed in δ values with reference to the residual solvent peaks
or TMS as internal standard. IR spectra were measured on Shimadzu prestige 21
FT-IR spectrophotometer. MS analysis was carried out on Agilent Technologies 1200
Series LC-MS system. UV-visible absorption spectra were measured in 1 cm quartz
cells on a UV 2450 spectrophotometer (JPN, SHIMADZU).
O2N
N
N
NH2
.
Fig. 1. Structure of C.I. Disperse Orange 3
2.2 Synthesis
Synthetic procedures for the six azo disperse dyes 3 are depicted in Scheme 2. The
sequence includes three steps: (1) Ugi four-component reaction; (2) selective amide
hydrolysis of Ugi products; and (3) coupling with aryl diazonium salts. It is

ACCEPTED MANUSCRIPT
noteworthy that direct azo coupling of an Ugi product with a diazonium salt was not
successful. Thus, a three-step sequence was employed.
2.2.1 Ugi four-component reaction
A general procedure for synthesis of 1a: A 250 mL round bottom flask was charged
with anhydrous methanol (150 mL), aniline (4.39 mL, 48.16 mmol, 1.05 eq),
p-methylbenzaldehyde (4.9 mL, 48.16 mmol, 1.05 eq), formic acid (2.07 mL, 55.04
mmol, 1.2 eq), and cyclohexyl isocyanide (5.69 mL, 45.87 mmol, 1.0 eq) sequentially.
The resultant mixture was heated at 80
in an oil bath for 48 h until the reaction
went to completion according to TLC analysis. The reaction mixture was firstly
cooled to room temperature, and then put in refrigerator to precipitate the product as a
white solid. The solid was obtained as the desired Ugi product 1a (7.09 g) through a
sequence of filtration, washing with a mixture of EtOAc and petroleum ether (1:5),
and drying under vacuum. The solvent of filtrate was then removed with rotavapor
under reduced pressure, and the other portion of product (4.66 g) was obtained with
1
high quality according to H NMR analysis. The overall yield of 1a was 73%. Ugi
product 1b was synthesized in 77% yield by following the same procedure as
described for 1a.
2.2.2 Selective amide hydrolysis of Ugi product
A general procedure for synthesis of 4a: A 100 mL round bottom flask was charged
with Ugi product 1a (7.09 g, 20.26 mmol) and methanol (70 mL), followed by slowly
adding a mixture of water (17.5 mL) and concentrated sulfuric acid (98%, 17.5 mL) at
room temperature. After stirring at 90 in an oil bath for 2 h, the reaction went to
completion according to TLC analysis. The reaction mixture was firstly neutralized
with aqueous NaOH (5 mol/L) and then extracted with ethyl acetate three times. The
organic layers were combined and then concentrated under reduced pressure. After
drying under vacuum, the hydrolysis product 4a (6.02 g, 92% yield) was obtained in
1
high quality according to H NMR analysis. The hydrolysis product 4b was
synthesized in 96% yield by following the same procedure as described for 4a.

ACCEPTED MANUSCRIPT
2.2.3 Coupling with diazonium salts (Synthesis of azo disperse dyes)
A general procedure for synthesis of azo disperse dye 3aa: A 50 mL round bottom
flask was charged with deionized water (4 mL), concentrated hydrochloric acid
(36.5%, 4 mL) and 4-nitroaniline (0.64 g, 4.65 mmol, 1.5 eq). The resultant mixture
was firstly heated at 40~60 for 2 h, then cooled to 0 in an ice bath. The mixture
was then treated with aqueous sodium nitrite (0.32 g, 4.65 mmol, 1.5 eq, 4 mL) and
stirred at the same temperature for 2 h to form 4-nitrophenyldiazonium salt 2a.
Diazonium salts 2b and 2c were synthesized by following the same procedure as
described for 2a. A 50 mL round bottom flask was charged with the hydrolysis
product 4a (1.00 g，3.10 mmol，1.0 eq), methanol (10 mL), deionized water (5 mL),
and acetic acid (2 mL). After cooling to 0 ℃in an ice bath, 4-nitrophenyldiazonium
salt prepared above was added slowly and the resultant mixture was stirred at room
temperature for 24 h until the coupling reaction went to completion according to TLC
analysis. The mixture was neutralized with aqueous NaOH (5 mol/L) and filtered. The
solid obtained was washed with a mixture of EtOAc and petroleum ether (1:5). After
recrystallization from ethyl acetate, followed by drying under vacuum, the desired azo
disperse dye 3aa was obtained (1.39 g, 95% yield). Azo disperse dyes 3ab (84%
yield), 3ac (84% yield), 3ba (74% yield), 3bb (81% yield), 3bc (75% yield) were
synthesized by following the same procedure as described for 3aa.

ACCEPTED MANUSCRIPT
Scheme 2. Synthesis of azo disperse dyes 3
2.3 Characterization
The structures of Ugi products (1a, 1b), hydrolysis products (4a, 4b), and the final
azo disperse dyes (3aa, 3ab, 3ac, 3ba, 3bb, 3bc) were ambiguously confirmed by 1H
NMR, 13C NMR, MS, and IR analysis.
N-Cyclohexyl-2-(N-phenylformamido)-2-(p-tolyl)acetamide 1a: white solid, 73%
o
yield, mp 163–164 C. IR λmax (KBr)/cm-1 3273, 3085, 2926, 1668, 1652, 1559, 700
1
cm-1. H NMR (400 MHz, CDCl3) δ ppm 8.39 (s, 1H), 7.26–7.24 (m, 3H), 7.19–7.16
(m, 2H), 7.12 (d, J = 8.0 Hz, 2H), 7.06 (d, J = 8.0 Hz, 2H), 5.96 (s, 1H), 5.77 (br d, J
= 8.0 Hz, 1H), 3.88-3.81 (m, 1H), 2.30 (s, 1H), 1.95–1.88 (m, 2H), 1.70–1.57 (m, 3H),
13
1.41–1.30 (m, 2H), 1.17–1.05 (m, 3H). C NMR (100 MHz, CDCl3) δ 168.1, 163.1,
139.5, 138.4, 131.2, 129.6 (×2), 129.3 (×2), 128.9 (×2), 128.2 (×2), 127.8, 63.6, 48.8,
32.8, 32.7, 25.5, 24.8, 24.7, 21.1. MS (+ESI): m/z (%) = 351 (100) [M+H+], 373 (60)
[M+Na+]. Found: C, 75.18; H, 7.45; N, 7.92%; C22H26N2O2 requires C, 75.40; H, 7.48;
N, 7.99%.
2-(2-Bromophenyl)-N-cyclohexyl-2-(N-phenylformamido)acetamide 1b: white solid,
o
77% yield, mp 166–167 C. IR λmax (KBr)/cm-1 3347, 2929, 1692, 1663, 766, 700
cm-1. 1H NMR (400 MHz, CDCl3) δ 8.42 (s, 1H), 7.50 (d, J = 6.8 Hz, 1H), 7.31–7.29
(m, 3H), 7.19–7.18 (m, 3H), 7.12–7.06 (m, 2H), 6.32 (s, 1H), 5.78 (d, J = 6.8 Hz, 1H),
3.89–3.87 (m, 1H), 2.06–1.92 (m, 2H), 1.75–1.60 (m, 3H), 1.37–1.35 (m, 2H),
1.25–1.06 (m, 3H). 13C NMR (100 MHz, CDCl3) δ.167.6, 163.0, 138.3, 133.5, 133.0,
131.8, 130.2, 128.7 (×2), 128.4 (×2), 127.9, 127. 3, 125.8, 62.5, 49.1, 32.7 (×2), 25.5,
24.8, 24.7. MS (+ESI): m/z (%) = 415 (100) [M+H+], 417 (100) [M+2+H+]. Found: C,
60.54; H, 5.53; N, 6.67%; C21H23BrN2O2 requires C, 60.73; H, 5.58; N, 6.74 %.
N-Cyclohexyl-2-(phenylamino)-2-(p-tolyl)acetamide 4a: white solid, 92% yield, mp
o
1
123–124 C. IR λmax (KBr)/cm-1 3300, 2930, 2854, 1647, 1505, 749 cm-1. H NMR
(400 MHz, CDCl3) δ 7.33 (d, J = 8.4 Hz, 2H), 7.23–7.19 (m, 4H), 6.82 (dd, J = 7.6,
7.2 Hz, 1H), 6.68 (br d, J = 7.6 Hz, 1H), 6.65 (d, J = 7.6 Hz, 2H), 4.69 (s, 1H),

ACCEPTED MANUSCRIPT
3.87–3.78 (m, 1H), 2.37 (s, 3H), 1.93–1.81 (m, 2H), 1.72–1.58 (m, 3H), 1.40–1.29 (m,
13
2H), 1.22–1.01 (m, 3H). C NMR (100 MHz, CDCl3) δ 170.2, 146.8, 138.3, 136.0,
129.8 (×2), 129.3 (×2), 127.3 (×2), 119.1, 113.9 (×2), 64.1, 48.1, 33.0, 32.8, 25.4,
24.8, 24.7, 21.2. MS (+ESI): m/z (%) =323 (100) [M+H+]. Found: C, 78.13; H, 8.08;
N, 8.75%; C21H26N2O requires C, 78.22; H, 8.13; N, 8.69%.
2-(2-Bromophenyl)-N-cyclohexyl-2-(phenylamino)acetamide 4b: white solid, 96%
o
yield, mp 134–135 C. IR λmax(KBr)/cm-1 3396, 3349, 2932, 1674, 1603, 1508, 747
cm-1. 1H NMR (400 MHz, CDCl3) δ 7.62 (d, J = 8.8 Hz, 1H), 7.49 (d, J = 9.2 Hz, 1H),
7.31 (d, J = 8.4, 7.6 Hz, 1H), 7.21–7.14 (m, 3H), 6.75 (dd, J = 7.2, 7.2 Hz, 1H), 6.57
(d, J = 8.4 Hz, 1H), 6.41 (br d, J = 7.2 Hz, 1H), 5.27 (s, 1H), 5.06 (br s, 1H),
3.86-3.78 (m, 1H), 1.97 (d, J = 15.2 Hz, 1H), 1.77–1.70 (m, 2H), 1.60–1.58 (m, 2H),
13
1.45–1.12 (m, 5H), 1.08–1.02 (m, 1H). C NMR (100 MHz, CDCl3) δ 169.0, 146.1,
138.5, 133.1, 129.8, 129.3, 128.7 (×2), 128.5, 123.8, 118.4, 113.5 (×2), 61.2, 48.4,
32.8, 32.5, 25.4, 24.5, 24.4. MS (+ESI): m/z (%) = 386 (100) [M+]. Found: C, 62.20;
H, 6.01; N, 7.27%; C20H23BrN2O requires C, 62.02; H, 5.99; N, 7.23%.
(E)-N-Cyclohexyl-2-((4-((4-nitrophenyl)diazenyl)phenyl)amino)-2-(p-tolyl)acetamide
3aa: dark red solid, 95% yield, mp 198–199 oC. IR λmax (KBr)/cm-1 3401, 2932, 1667,
1
1515, 1339, 1141, 860 cm-1. H NMR (400 MHz, CDCl3) δ ppm 8.34 (d, J = 9.2 Hz,
2H), 7.93 (d, J = 9.2 Hz, 2H), 7.84 (d, J = 9.2 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.23
(d, J = 8.0 Hz, 2H), 6.68 (d, J = 8.8 Hz, 2H), 5.89 (br d, J = 8.4 Hz, 1H), 5.66 (d, J =
3.6 Hz, 1H), 4.85 (d, J = 3.6 Hz, 1H), 3.84–3.76 (m, 1H) , 2.38 (s, 3H), 1.93 (d, J =
12.0 Hz, 1H), 1.78–1.58 (m, 4H), 1.39-1.32 (m, 2H), 1.20–1.11 (m, 2H), 1.04-0.95 (m,
13
1H). C NMR (100 MHz, CDCl3) δ 169.1, 156.5, 150.4, 147.7, 145.4, 138.7, 135.3,
130.2 (×2), 127.0 (×2), 126.0 (×2), 124.7 (×2), 122.8 (×2), 113.5 (×2), 62.1, 48.6,
32.9, 32.6, 25.3, 24.7, 24.5, 21.2.MS (+ESI): m/z (%) = 588 (100), 472 (35) [M+H+].
Found: C, 68.93; H, 6.25; N, 14.80%; C27H29N5O3 requires C, 68.77; H, 6.20; N,
14.85%.
(E)-N-Cyclohexyl-2-((4-((2,6-dichloro-4-nitrophenyl)diazenyl)phenyl)amino)-2-(p-tol
o
yl)acetamide 3ab: red solid, 84% yield, mp 215–216 C. IR λmax(KBr)/cm-1 2984,
1739, 1373, 1238, 1046 cm-1. 1H NMR (400 MHz, CDCl3) δ 8.26 (s, 2H), 7.83 (d, J =

ACCEPTED MANUSCRIPT
8.8 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 6.67 (d, J = 8.8 Hz,
2H), 5.92 (d, J = 8.0 Hz, 1H), 4.88 (s, 1H), 3.84–3.75 (m, 1H), 2.37 (s, 3H), 1.94 (d, J
= 9.2 Hz, 1H), 1.77–1.68 (m, 2H), 1.60 (d, J = 10.0 Hz, 2H), 1.40–1.25 (m, 2H),
13
1.18–1.12 (m, 2), 1.02–0.96 (m, 1H). C NMR (100 MHz, CDCl3) δ 169.0, 153.8,
151.1, 145.3, 144.9, 138.8, 135.2, 130.2 (×2), 127.9 (×2), 127.0 (×2), 126.2 (×2),
124.2 (×2), 113.3 (×2), 61.7, 48.8, 32.9, 32.6, 25.3, 24.7, 24.6, 21.2. MS (+ESI): m/z
(%) = 392 (100), 540 (52) [M+H+]. Found: C, 59.98; H, 5.03; N, 12.92%;
C27H27Cl2N5O3 requires C, 60.01; H, 5.04; N, 12.96%.
(E)-2-((4-((2-Chloro-4-nitrophenyl)diazenyl)phenyl)amino)-N-cyclohexyl-2-(p-tolyl)a
o
cetamide 3ac: dark red solid, 84% yield, mp 149–151 C. IR λmax(KBr)/cm-1 3389,
3341, 2928, 1687, 1603, 1516, 1142 cm-1. 1H NMR (400 MHz, CDCl3) δ 8.38 (d, J =
2.0 Hz, 1H), 8.14 (dd, J = 8.8, 2.4 Hz, 1H), 7.86 (d, J = 8.8 Hz, 2H), 7.74 (d, J = 8.8
Hz, 1H), 7.35 (d, J = 8.0 Hz, 2H), 7.22 (d, J = 7.6 Hz, 2H), 6.67 (d, J = 8.8 Hz, 2H),
5.87 (br s, 1H), 5.85 (br s, 1H), 4.87 (s, 1H), 3.83–3.76 (m, 1H), 2.37 (s, 3H), 1.94 (d,
J = 9.2 Hz, 1H), 1.77–1.68 (m, 2H), 1.60 (d, J = 12.0 Hz, 2H), 1.42–1.28 (m, 2H),
13
1.21–1.12 (m, 2H), 1.04–0.96 (m, 1H). C NMR (100 MHz, CDCl3) δ 169.0, 152.9,
150.8, 147.5, 145.8, 138.7, 135.3, 134.3, 130.2 (×2), 127.0 (×2), 126.0, 122.6 (×2),
118.1, 113.5 (×2), 61.8, 48.7, 32.9, 32.6, 25.3, 24.7, 24.5, 21.2. MS (+ESI): m/z (%) =
506 (15) [M+H+], 529 (100). Found: C, 64.25; H, 5.59; N, 13.89%; C27H28ClN5O3
requires C, 64.09; H, 5.58; N, 13.84%;
(E)-2-(2-Bromophenyl)-N-cyclohexyl-2-((4-((4-nitrophenyl)diazenyl)phenyl)amino)a
o
cetamide 3ba: dark red solid, 74% yield, mp 153–154 C. IR λmax(KBr)/cm-1 3308,
1
2930, 1676, 1601, 1333, 1136 cm-1. H NMR (400 MHz, CDCl3) δ ppm 8.33 (d, J =
8.8 Hz, 2H), 7.91 (d, J = 8.8 Hz, 2H), 7.83 (d, J = 8.8 Hz, 2H), 7.66 (dd, J = 8.0, 0.8
Hz, 1H), 7.49 (dd, J = 7.6, 1.6 Hz, 1H), 7.33 (dd, J = 7.6, 7.6 Hz, 1H), 7.22 (ddd, J =
7.6, 7.6, 1.2 Hz, 1H), 6.60 (d, J = 8.8 Hz, 1H), 6.12 (d, J = 4.8 Hz, 1H), 6.10 (d, J =
7.6 Hz, 1H), 5.45 (d, J = 4.8 Hz, 1H), 3.84–3.75 (m, 1H), 1.99–1.95 (m, 1H),
1.73–1.69 (m, 2H), 1.62–1.57 (m, 2H), 1.46–1.19 (m, 4H), 1.11–1.01 (m, 1H). 13C
NMR (100 MHz, CDCl3) δ 167.8, 156.3, 149.7, 147.6, 145.0, 137.6, 133.2, 130.2,
128.9, 128.3, 126.4, 124.7, 123.2, 122.7, 113.3, 59.4, 48.7, 32.7, 32.3, 25.3, 24.4, 24.3.

ACCEPTED MANUSCRIPT
MS (+ESI): m/z (%) = 536 (45) [M+H+], 538 (53) [M+2+H+]. Found: C, 58.09; H,
4.94; N, 13.13%; C26H26BrN5O3 requires C, 58.22; H, 4.89; N, 13.06%.
(E)-2-(2-Bromophenyl)-N-cyclohexyl-2-((4-((2,6-dichloro-4-nitrophenyl)diazenyl)ph
o
enyl)amino)acetamide 3bb: red solid, 81% yield, mp 215–216 C. IR λmax(KBr)/cm-1
1
2927, 1602, 1515, 1137, 906, 780 cm-1. H NMR (400 MHz, CDCl3) δ 8.26 (s, 2H),
7.83 (d, J = 8.8 Hz, 2H), 7.66 (dd, J = 8.0, 1.2 Hz, 1H), 7.49 (dd, J = 7.6, 1.6 Hz, 1H),
7.34 (dd, J = 6.8, 6.8 Hz, 1H), 7.23 (ddd, J = 8.0, 8.0, 2.0 Hz, 1H), 6.60 (d, J = 8.8 Hz,
2H), 6.26 (d, J = 4.8 Hz, 1H), 6.08 (d, J = 8.0 Hz, 1H), 5.47 (d, J = 4.8 Hz, 1H),
3.83–3.75 (m, 1H), 1.99-1.95 (m, 1H), 1.72–1.69 (m, 2H), 1.62–1.56 (m, 2H),
13
1.43–1.19 (m, 4H), 1.11–1.01 (m, 1H). C NMR (100 MHz, CDCl3) δ 167.7, 153.8,
150.2, 145.3, 144.8, 137.6, 133.2, 130.2, 128.9, 128.3, 127.9, 126.4, 124.2, 123.1,
113.1, 59.2, 48.7, 32.7, 32.3, 29.7, 26.9, 25.3, 24.4, 24.3. MS (-ESI): m/z (%) = 602
(75) [M-H+], 604 (100), 606 (39). Found: C, 51.54; H, 3.94; N, 11.42%;
C26H24BrCl2N5O3 requires C, 51.59; H, 4.00; N, 11.57%.
(E)-2-(2-Bromophenyl)-2-((4-((2-chloro-4-nitrophenyl)diazenyl)phenyl)amino)-N-cyc
o
lohexylacetamide 3bc: dark red solid, 75% yield, mp 180–181 C. IR λmax(KBr)/cm-1
1
3406, 3324, 1677, 1604, 1519, 1137, 1114 cm-1. H NMR (400 MHz, CDCl3) δ 8.39
(d, J = 2.0 Hz, 1H), 8.15 (dd, J = 8.8, 2.0 Hz, 1H), 7.86 (d, J = 8.4 Hz, 2H), 7.74 (d, J
= 8.8 Hz, 1H), 7.66 (d, J = 7.6 Hz, 1H), 7.48 (d, J = 7.2 Hz, 1H), 7.33 (dd, J = 8.0, 8.0
Hz, 1H), 7.23 (dd, J = 8.0, 8.0 Hz, 1H), 6.59 (d, J = 8.8 Hz, 2H), 6.25 (br d, J = 4.4
Hz, 1H), 6.10 (br d, J = 8.0 Hz, 1H), 5.47 (d, J = 4.8 Hz, 1H), 3.83–3.76 (m, 1H), 1.97
13
(d, J = 9.2 Hz, 1H), 1.71–1.57 (m, 4H), 1.45–1.19 (m, 4H), 1.10–1.02 (m, 1H). C
NMR (100 MHz, CDCl3) δ 167.7, 152.9, 150.0, 147.5, 145.7, 137.6, 134.2, 133.2,
130.2, 128.9, 128.3, 126.8, 126.0, 123.1, 122.6, 118.1, 113.3, 59.3, 48.7, 32.7, 32.3,
25.3, 24.4, 24.2. MS (-ESI): m/z (%) = 568 (57) [M-H+], 570 (100). Found: C, 54. 59;
H, 4.48; N, 12.34%; C26H25BrClN5O3 requires C, 54.70; H, 4.41; N, 12.27%.
2.4. Dyeing and fastness measurement
The PET and PA fibers used in this study were provided by Zhejiang Longsheng

ACCEPTED MANUSCRIPT
Chemical Co., Ltd. (China). The PA fibers were scoured with 2 g/L of soap powder
and 1 g/L of sodium carbonate at 100 °C for 30 minutes before use, and the bath ratio
was 30:1, then rinsed with water and dried at room temperature.
The purified dyes and dispersing agent MF (weight ratio 1:1) were milled to dye
dispersions having an average particle size of less than 0.5µm. For each of new dyes,
a series of dye baths containing different initial concentration of dye ranging from
0.125% to 5% o.w.f and 1 g/L ammonium sulfate were prepared, respectively, and all
the liquor ratios were 100:1. Dyeings were performed in an IR laboratory dyeing
machine (RAPID, China). The dyeing procedure on PET fibers was carried out by
raising the dye bath temperature from 70 °C to 130 °C at a rate of 1 /min,
maintained at this temperature for 180 min, and then reduced to 85 . The dyeing
process on PA fibers was started at 40 , and the temperature was raised from 40 to
110
at rate of 1 /min, maintained for 60 min at the final temperature, and then
reduced to 85 . In order to remove the adsorbed dyestuff molecules from the dyed
fabrics, dyed PET and PA fibers were cleaned through reduction with an aqueous
solution containing sodium hydroxide (2 g/L) and sodium hydrosulphite (2 g/L) at
85 using a liquor ratio of 50:1 for 15 min, and then rinsed with water and dried at
room temperature. Dyeings of 1:1 standard depth on PET and PA fibers for each of
dyes were obtained.
The test methods used for measurement of fastness were ISO 105-C06 for washing,
ISO 105-X12 for rubbing, and ISO 105-P01 for sublimation.
3. Results and discussion
3.1 Spectra properties
Visible absorption experiments of C.I. Disperse Orange 3, 3aa, 3ab, 3ac, 3ba, 3bb,
and 3bc were carried out and the results are summarized in Table 1. Compared azo
disperse dye 3aa with 3ba, 3ab with 3bb, and 3ac with 3bc, it is evident that the
maximum visible absorption wavelengths are similar. Thus, we can conclude that the

ACCEPTED MANUSCRIPT
coupling partner obtained through a sequence of Ugi-4CR and hydrolysis is very
suitable for synthesizing a library of structurally diverse and molecular weight/size
controlled azo disperse dyes. On the other hand, comparing azo disperse dyes 3aa,
3ab, and 3ac (or 3ba, 3bb, and 3bc), the maximum visible absorption wavelengths
are quite different, indicating the color of the azo disperse dye obtained is mainly
dependent on diazonium salt counterparts. Therefore, a broad range of colors can be
achieved by tuning the electron-withdrawing properties of the substitutions on
diazonium salt counterparts. It is noteworthy that the dichloro-substituted dyes 3ab
and 3bb show hypsochromic shift as comparing with nonchloro-substituted dyes 3aa
and 3ba, which is reasoned by the fact that benzene rings on both sides of -N=N-
group were twisted to a certain extent and the conjugation of donor-π-acceptor system
was lowered due to the steric hindrance of two chlorine substitutions at the ortho
positions of diazonium group.
Table 1 Visible absorption of C.I. Disperse Orange 3, 3aa, 3ab, 3ac, 3ba, 3bb, and
3bc in DMF.
dyes
λmax
467
464
420
489
461
416
484
W1/2(nm) a
Ɛ(l·mol-1·cm-1)
C.I. Disperse Orange 3
123
30777
3aa
124
29393
3ab
144
23891
3ac
124
38512
3ba
116
34323
3bb
142
26158
3bc
125
36237
a W1/2:Peak width at half height.
3.2 Fastness properties
The color fastness testing results of C.I. Disperse Orange 3, 3aa, 3ab, 3ac, 3ba,
3bb, 3bc on nylon and PET fibers are shown in Tables 2 and 3, respectively. As

ACCEPTED MANUSCRIPT
shown in Table 2, the washing and sublimation fastness properties of C.I. Disperse
Orange 3 on nylon were extremely poor, especially, the grades of staining ratings on
acetate cellulose and nylon were only 1, while the grade of the staining rating of
sublimation was 1-2. To our delight, it was found that both the washing and
sublimation fastness properties of the synthesized dyes 3aa, 3ab, 3ac, 3ba, 3bb, 3bc
on nylon were good to excellent. Particularly, the staining ratings on acetate cellulose
and nylon were increased from 1 to 3, or even higher than 3, and the staining ratings
of sublimation were improved to 4-5, or even 5. Similarly, the six synthesized dyes
also exhibited excellent washing and sublimation fastness on PET fiber as shown in
Table 3. It was noteworthy that the staining ratings of sublimation on PET were
greatly improved to 4, or even higher, as compared with that of C.I.Disperse Orange 3.
We reasoned that the improvements should be attributed to appropriate increase of the
dye molecular weight/size and the amide functionality introduced in Ugi reaction,
resulting in the enhanced van der Waals force and the formation of hydrogen-bonding
interaction of dyes with fibers, respectively.
Table 2. Fastness testing of C.I.Disperse Orange 3, 3aa, 3ab, 3ac, 3ba, 3bb, and 3bc
on nylon fibers.
Dyes
Washing fastness
Staining
Sublimation fastness
Shade change
Shade change Staining
1
1
2
3
1
3
5
3
3
4
5
6
Orange 3
3aa
4
4
3-4
2-3 3-4 2-3
3-4
4-5
4-5
4-5
4
1-2
4-5
4-5
4-5
5
3-4 4-5
3-4 4-5
3-4
4
4-5
4-5
4
5
5
5
4-5
3ab
3-4 4-5
3-4 4-5 3-4
3-4 4-5 3-4
3ac
4
4-5
5
3ba
4
5
4-5 4-5
3-4
5
4-5
4-5
4-5
5
3bb
4-5
4-5
5
4
4-5 4-5
5
3bc
1: staining acetate cellulose; 2: staining cotton; 3: staining nylon; 4: staining polyester; 5: staining

ACCEPTED MANUSCRIPT
polyacrylonitrile; 6: staining wool.
Table 3 Fastness testing of C.I.Disperse Orange 3, 3aa, 3ab, 3ac, 3ba, 3bb, and 3bc
on PET fibers.
Dyes
Washing fastness
Staining
Sublimation fastness
Shade change
Shade change Staining
1
4
5
5
5
5
5
5
2
5
5
5
5
5
5
5
3
4
5
5
4
5 6
Orange 3
3aa
4-5
4-5
5
4-5 5 4-5
5
4-5
5
1
4
5
5
5 4-5
5 4-5
5
3ab
5
4-5 4-5 5 4-5
5
4-5
4
3ac
4-5
4-5
5
4-5
5
5
5
5
5 4-5
5 4-5
5 4-5
5
3ba
4-5
4-5
5
3bb
5
4-5
3bc
1: staining acetate cellulose; 2: staining cotton; 3: staining nylon; 4: staining polyester; 5: staining
polyacrylonitrile; 6: staining wool
4. Conclusion
In conclusion, we have developed a novel and general protocol for efficient
synthesis of structurally diverse azo disperse dyes with good to excellent fastness
properties though a sequence of Ugi four-component reaction, selective hydrolysis of
amide, and azo coupling with diazonium salts. Introducing the Ugi four-component
reaction in disperse dye synthesis has advantages of easy tuning the dye molecular
weight/size, introducing amide functionality for forming hydrogen-bonding
interactions with fiber, and achieving structural diversity of the final azo disperse dyes
for screening. It has been demonstrated that six azo disperse dyes obtained through
the protocol exhibited good to excellent color fastness on both nylon and PET fibers.
The improved fastness properties should be attributed to the appropriate increased
molecular weight/size and the introduced amide functionality in Ugi four-component

ACCEPTED MANUSCRIPT
reaction. Thus, it is an appealing new protocol for synthesizing a library of azo
disperse dyes with excellent fastness properties and will be of significant value
towards practical application.
Acknowledgements
We gratefully acknowledge the financial support from the National Natural Science
Foundation of China (21376149 and 21676166).
References:
[1] Hussain T, Tausif M, Ashraf M. A review of progress in the dyeing of eco-friendly
aliphatic polyester-based polylactic acid fabrics. Dyes and Pigments
2015;108:476–83.
[2] Ameuru US, Yakubu MK, Bello KA, Nkeonye PO, Halimehjani AZ. Synthesis of
disperse dyes derived from 4-amino-N-decyl-1,8-naphthalimide and their dyeing
properties on polyester fabrics. Dyes and Pigments 2018;157:190–7.
[3] Tumer M, Tumer F, Kose M, Gungor SA, Akar S, Demirtas I, Ceyhan G.
Structural characterizations, photophysical and biological properties of disperse
black 9 dye and π-extended imine derivatives. Dyes and Pigments
2018;154:62–74.
[4] Jiang H, Zhang L, Cai J, Ren J, Cui Z, Chen W. Quinoidal bithiophene as disperse
dye: Substituent effect on dyeing performance. Dyes and Pigments
2018;151:363–71.
[5] Towns AD. Developments in azo disperse dyes derived from heterocyclic diazo
components. Dyes and Pigments 1999;42(1):3–28.
[6] Qiu J, Xiao J, Tang B, Ju B, Zhang S. Facile synthesis of novel disperse azo dyes
with aromatic hydroxyl group. Dye and Pigments 2019;160:524–9.
[7] Feng G, Qian H-F, Bai G, Liu Y-C, Hu L-L. Synthesis, characterization, and
application of diester/diurethane tethered azo disperse dyes: A new strategy to
improve dye’s fastness properties. Dyes and Pigments 2016;129:54–9.

ACCEPTED MANUSCRIPT
[8] Qian H-F, Feng G, Bai G, Liu Y-C, Hu L-L. A contrastive study of adsorption
behaviors on polyurethane fiber with diester/diurethane tethered and non-tethered
azo disperse dyes. Dyes and Pigments 2017;145:301–6.
[9] Kim SD, Kim MJ, Lee BS, Lee KS. Effects of thermomigration on the
washfastness of disperse dyes having different molecular size. Fibers Polym
2004;5(1):39–43.
[10] Sokolowaka J, Podsiadly R, Sochocka E. Synthesis and properties of some
disazo disperse dyes derivatives of 2-amino-6-phenylazothiazole and 2-
amino-6-(4’-nitro)-phenylazobenzothiazole.
2007;72(2):223–7.
Dyes
and
Pigments
[11] Patel DM, Patel TS, Dixit BC. Synthesis, characterization and dyeing
performance of new bisazoebisazomethine disperse dyes. J Saudi Chem Soc
2013;17(2):203–9.
[12] Hu XH, Zhang XY, Liu J, Dai JB. Synthesis, characterization and fluorescence
performance of a waterborne polyurethane-based polymeric dye. J Luminescence
2013;142:23-7
[13] Joshi M, Jauhari S, Desai KR. Polyurethanes as polymerizable dyes for
hydrophobic polyester fabric. Res Chem Intermed 2012; 38(9): 2137–48.
[14] Martin DB, Schreiber SL. A planning strategy for diversity-oriented synthesis.
Angew Chem Int Ed 2004; 43(1):46–58.
[15] Liu T, Jia, W, Xi Q, Chen Y, Wang X, Yin D. Diversity-oriented synthesis of
heterocycles: Al(OTf)3-promoted cascade cyclization and ionic hydrogenation. J
Org Chem 2018;83(3):1387–93.
[16] Contreras-Cruz DA, Sánchez-Carmona MA, Vengoechea-Gómez FA, Peńa-Ortíz
D, Luis D. Miranda LD. Diversity-oriented synthesis of cyclopropyl peptides
from Ugi-derived dehydroalanines. Tetrahedron 2017;73(43):6146–56.
[17] Bhojgude SS, Bhunia A, Biju AT. Employing arynes in Diels–Alder reactions and
transition-metal-free multicomponent coupling and arylation reactions. Acc
Chem Res 2016;49(9):1658–70.

ACCEPTED MANUSCRIPT
[18] Reguera L, Méndez Y, Humpierre AR, Valdés O, Rivera, DG. Multicomponent
reactions in ligation and bioconjugation chemistry. Acc Chem Res
2018;51(6):1475–86.
[19] Shi J, Wu J, Cui C, Dai W.-M. Microwave-assisted intramolecular Ullmann
diaryl etherification as the post-Ugi annulation for generation of
dibenz[b,f][1,4]oxazepine scaffold: J Org Chem 2016;81(21):10392–403.
[20] Wang G, Liu C, Li B, Wang Y, Hecke KV, Van der Eycken EV, Pereshivko OP.
Peshkov VA. Diversity-oriented synthesis of 1,3-benzodiazepines. Tetrahedron
2017;73(44):6372–80.
[21] Kong HH, Pan HL, Ding MW. Synthesis of 2-tetrazolyl-substituted
3-acylpyrroles
cycloisomerization reaction. J Org Chem 2018;83(20):12921–30.
[22] Zhang J, Yu P, Li S-Y, Sun H, Xiang S-H, Wang J, Houk KN, Tan B. Asymmetric
phosphoric acid–catalyzed four-component Ugi reaction. Science
2018;DOI:10.1126/science.aas8707.
via
a
sequential
Ugi-azide/Ag-catalyzed
oxidative
[23] Madhavachary R, Zarganes-Tzitzikas T, Patil P, Kurpiewska K,
Kalinowska-Tłuścik J, Dömling A. Synthesis of highly substituted imidazole
uracil containing molecules via Ugi-4CR and Passerini-3CR. ACS Comb Sci
2018;20(4):192–6.
[24] Hoffer L, Voitovich YV, Raux B, Carrasco K, et al. Integrated strategy for lead
optimization
based
on
fragment
approach.
growing:
Med
The
diversity-oriented-target-focused-synthesis
2018;61(13):5719–32.
J
Chem
[25] Katsuyama A, Yakushiji F, Ichikawa S. Total synthesis of plusbacin A3 and its
dideoxy derivative using a solvent-dependent diastereodivergent Joullié–Ugi
three-component reaction. J Org Chem 2018;83(13):7085–101.
[26] Brown AL, Churches QI, Hutton CA. Total synthesis of ustiloxin D utilizing an
ammonia–Ugi reaction. J Org Chem 2015; 80(20): 9831–7.
[27] Shen H, Ma H, Liu P, Huang W, Han L, Li C, Li Y. Facile Synthesis of in-Chain,
multicomponent, functionalized polymers via living anionic copolymerization

ACCEPTED MANUSCRIPT
through the Ugi four-component reaction (Ugi-4CR). Macromol Rapid Commun
2017;38(18):1700353.
[28] Sehlinger A, Verbraeken B, Meier M. A. R. Hoogenboom R. Versatile side chain
modification via isocyanide-based multicomponent reactions: tuning the LCST
of poly(2-oxazoline)s. Polym Chem 2015;6(20):3828–36.
[29] Kakuchi R. Multicomponent reactions in polymer synthesis. Angew Chem Int Ed
2014;53(1):46–8.

ACCEPTED MANUSCRIPT
Highlights:
1. Diversity-oriented synthesis of azo disperse dyes was achieved through employing
Ugi four-component reaction.
2. The new approach featured easy control of molecular weight/size and introduction
of amide functionality in the final dye.
3. Dramatically improved fastness properties of the new azo disperse dyes were
observed.
4. Improvements were attributed to both the increased van der Waals force and the
formation of hydrogen-bonding interaction of dyes with fibers.
5. It is an attractive approach to synthesize a library of structurally diverse azo
disperse dyes for screening.