Br?nsted acid-catalyzed chlorination of aromatic carboxylic acids

Article abstract of DOI:10.1080/10426507.2021.1903008

The chlorination of aromatic carboxylic acids with SOCl₂ has been effectively performed by reacting with a Br?nsted acid as the catalyst. Based on this discovery, an efficient catalytic method that is cheaper than traditional catalytic methods was developed. 20 substrates were chlorinated offering excellent yields in a short reaction time. And the SOCl₂/Br?nsted acid system has been used in a larger scale preparative reaction. A dual activation mechanism was proposed to prove the irreplaceable system of SOCl₂/Br?nsted acid.

Full text of DOI:10.1080/10426507.2021.1903008

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/gpss20
Brønsted acid-catalyzed chlorination of aromatic
carboxylic acids
Zhiqun Yu, Hongmiao Yao, Qilin Xu, Jiming Liu, Xingmao Le & Minna Ren
To cite this article: Zhiqun Yu, Hongmiao Yao, Qilin Xu, Jiming Liu, Xingmao Le & Minna Ren
(2021): Brønsted acid-catalyzed chlorination of aromatic carboxylic acids, Phosphorus, Sulfur, and
Silicon and the Related Elements, DOI: 10.1080/10426507.2021.1903008
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PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
https://doi.org/10.1080/10426507.2021.1903008
Brønsted acid-catalyzed chlorination of aromatic carboxylic acids
Zhiqun Yua , Hongmiao Yaoa, Qilin Xub, Jiming Liub, Xingmao Lea, and Minna Rena
aCollaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou,
b
P. R. China; College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, P. R. China
ABSTRACT
ARTICLE HISTORY
Received 8 January 2021
Accepted 9 March 2021
The chlorination of aromatic carboxylic acids with SOCl2 has been effectively performed by react-
ing with a Brønsted acid as the catalyst. Based on this discovery, an efficient catalytic method that
is cheaper than traditional catalytic methods was developed. 20 substrates were chlorinated offer-
ing excellent yields in a short reaction time. And the SOCl2/Brønsted acid system has been used in
a larger scale preparative reaction. A dual activation mechanism was proposed to prove the irre-
placeable system of SOCl2/Brønsted acid.
KEYWORDS
Brønsted acid-catalyzed;
aromatic carboxylic acid;
thionyl chloride;
chlorination
GRAPHICAL ABSTRACT
Aromatic acyl chlorides, in light of their strong electrophi- Apart from these catalysts, no other types of catalysts have
been reported.
licity, can be easily converted into various acyl deriva-
tives,[1] which are widely employed in drugs,[2]
pesticides,[3] dyes,[4] and high-performance fibers.[5]
Consequently, significant efforts have been focused on
developing an efficient synthesis of aromatic acyl chlor-
ide.[1,6] Presently, aromatic acyl chlorides are mainly pre-
pared by reaction of aromatic carboxylic acids with
chlorination reagents, commonly including sulfoxide
chloride (SOCl2), phosphorus oxychloride (POCl3), phos-
phorus pentachloride (PCl5), phosphorus trichloride
(PCl3), phosgene (COCl2), triphosgene (BTC), carbon
tetrachloride (CCl4), and Vilsmeier reagent.[6b,7] Among
these chlorination reagents, SOCl2 possesses the advan-
tages of low cost and high efficiency.[8] For the chlorin-
ation employing SOCl2, organic base catalysts (such as
DMF and pyridine),[9] phase transfer catalysts (such as
benzyl triethylammonium chloride (BTAC) and tetrabuty-
lammonium chloride (TBAC)),[10] and Fe-catalysts (such
Herein, a new type of catalyst that can be used to catalyze
the chlorination of aromatic carboxylic acids with SOCl2
was reported. Ccommon Brønsted acids, such as sulfuric
acid (H2SO4), chlorosulfonic acid (ClSO3H), trifluorometha-
nesulfonic acid (CF3SO3H), and methylsulfonic acid
(CH3SO3H) were found to be able to catalyze the chlorin-
ation of carboxylic acids with SOCl2 efficiently. Based on
this discovery, we have developed an efficient catalytic
method that is much cheaper than traditional catalytic
methods (see Figure S1, Supplemental Materials).
During our pilot-scale process of the production of
Dinitroamine (DTO), a veterinarian drug against coccidiosis
(Scheme 2),[12] an abnormal increase in the chlorination rate
of 1-methyl-3,5-dinitrobenzoic acid (1a) was observed in the
absence of a catalyst, and we hypothesized that residual
H2SO4 acted as a catalyst.1 A series of experiments were
then carried out for verifying this conjecture, where 1a and
SOCl2 were selected as the model chlorination condition,
as FeCl3 and FeC6H5O7)[11] are often used as catalysts. some acids and DMF were tested as catalysts respectively.
CONTACT Zhiqun Yu
yzq@zjut.edu.cn
Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of
Technology, Hangzhou 310014, P. R. China.
Supplemental data for this article is available online at https://doi.org/10.1080/10426507.2021.1903008.
1During our pilot-scale chlorination process of the production of Dinitroamine, the catalyst DMF was accidentally omitted, leading to a rapid reaction in 3–4 h,
which was distinctly different from the laboratory test. In the laboratory test, the chlorination of 1-methyl-3,5-dinitrobenzoic acid (1a) would take at least 8-10 h
without catalyst. By examining the operation process, it was found that the remained unwashed H2SO4 in the reaction still might play the role of catalyst in the
chlorination process; While in the laboratory, the residual H2SO4 was always sufficiently washed and removed.
ß 2021 Taylor & Francis Group, LLC

2
Z. YU ET AL.
As shown in Table 1, 1a was converted entirely into 2a in but only 5% and 3% conversions were obtained (Table 1,
14 min under the catalysis of H2SO4 (Table 1, entry 3). entries 4–5). And good conversions were not obtained
And the reaction proceeded with difficulty without the with an increase of the amount of catalyst or reaction time
presence of a catalyst (Table 1, entry 2), which proved that
H2SO4 possessed the relative catalytic effect, although the
effect was slightly inferior to DMF (Table 1, entry 3 vs
entry 1). Encouraged by this promising result, other
Brønsted acids such as HNO3 and CF3COOH were tested,
(Supplementary material Table S1). Based on the above
results, we decided to narrow the scope of Brønsted acids’
screening, so some sulfonic acids such as CH3SO3H,
CF3SO3H, chlorosulfonic acid (ClSO3H), p-toluenesulfonic
acid (p-TsOH), and p-chlorobenzenesulfonic acid (PCBSA)
were tested and moderate to excellent results were
obtained (Table 1, entries 6–10). This proved that
Brønsted acids containing sulfonic acid groups can cata-
lyze the chlorination of aromatic carboxylic acids with
SOCl2. Among all the Brønsted acids tested, chlorosulfonic
acid (ClSO3H) has the best catalytic effect, and H2SO4 is
second only to ClSO3H. Considering that H2SO4 is a very
cheap chemical product, its price is far lower than that of
Table 1. Screening of chlorination catalystsa.
Conv. (%)
Time to >98%
Conv. (min)b
Entry
Catalyst
10 minb
1
2
3
4
5
6
7
8
DMF
–
H2SO4
85
2
60
4
4
23
27
81
10
13
12
N/Ac
14
HNO3
N/Ac
N/Ac
35
CF3COOH
CH3SO3H
CF3SO3H
ClSO3H
p-TsOH
PCBSA
32
12
260
210
9
10
aReaction conditions: 1a (2.26 g, 0.01 mol), SOCl2 (6 eq), Catalyst (0.05 eq).
bDetermined by HPLC. Corresponding acyl chloride was derivatized to the
ester (3a) with methanol.
cConversion did not reach 98% within 4 h.
dPCBSA: 4-chlorobenzenesulfonic acid.
Scheme 1. Chlorination methods of carboxylic acids.
Scheme 2. Scale preparative reactions.

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
3
Scheme 3. Plausible mechanism chlorination of 1a catalyzed by R-SO3H.
Table 2. Screening of chlorination reagentsa.
Table 3. Substrate expansion of Sulfuric acid-catalyzed chlorination of carbox-
ylic acidsa.
Yield without
Entry
R
time
Yield (%)b
catalyst (%)c
Chlorination
reagent
Conv. (%)
Time to >98%
Conv. (min)b
Entry
Catalyst
10 minb
1
2
3
4
5
6
7
8
3,5-dinitrophenyl
3-nitrophenyl
2- chlorophenyl
4-bromophenyl
17
7
6
97 (3b)
93 (3c)
92 (3d)
94 (3e)
93 (3f)
92 (3g)
94 (3h)
93 (3i)
2
5
19
12
10
6
12
7
9
44
55
52
56
1
2
3
4
5
6
7
8
DMF
H2SO4
–
DMF
H2SO4
–
DMF
H2SO4
–
DMF
H2SO4
–
POCl3
POCl3
POCl3
COCl2
COCl2
COCl2
PCl3
61
32
2
100
4
4
7
4
3
20
41
8
N/Ac
5
4-fluorophenyl
11
12
8
11
10
6
5
5
4
23
27
36
51
15
10
2,4-difluorophenyl
2,4-dichloro-5-fluorophenyl
4-(trifluoromethyl)phenyl
4-cyanophenyl
N/Ac
N/Ac
N/Ac
N/Ac
N/Ac
68
9
97 (3j)
97 (3k)
95 (3l)
PCl3
10
11
12
13
14
15
16
17
18
19
Phenyl
9
PCl3
2-methylphenyl
3-methylphenyl
naphthyl
4-carboxynaphthyl
3-carboxyphenyl
4-carboxyphenyl
3,5-dicarboxyphenyl
2-methoxyphenyl
3,4-dimethoxyphenyl
10
11
12
BTCd
BTCd
BTCd
38
12
12
89 (3m)
92 (3n)
95 (3o)
95 (3p)
96 (3q)
97 (3r)
N/Ac
N/Ac
N/Ad
N/Ad
N/Ad
N/Ad
28
aReaction conditions: 1a (2.26 g, 0.01 mol), chlorination reagent (6 eq), Catalyst
(0.12 eq).
bDetermined by HPLC. Corresponding acyl chloride was derivatized to the
ester (3a) with methanol.
45 (94e) (3s)
37 (93e) (3t)
cConversion did not reach 98% within 4 h.
25
dReaction conditions: 1a (2.26 g, 0.01 mol), BTC (3.3 ꢀ 10ꢁ3 mol), toluene
(6 mL) as solvent.
aReaction conditions: aromatic monocarboxylic acid (3, 0.01 mmol), SOCl2 (6
eq), and H2SO4 (0.12 eq), reflux for several minutes and the products were
derived as ester.
bIsolated yields.
cChlorination yields of some substrates without catalyst in the same reac-
traditional chlorination catalysts (such as DMF, pyridine
and BTAC, etc.),2 developing a chlorination strategy with
H2SO4 as a catalyst is bound to reduce the cost of chlorin-
ation of aromatic carboxylic acids. Therefore, we immedi-
ately investigated the influence of H2SO4 dosage on the
reaction (Supplementary material Table S1). The results
showed that when the dosage of H2SO4 reached 0.12 eq,
the best catalytic effect can be achieved, and if the dosage
continues to increase, the catalytic effect did not improve.
Next, we continued to explore whether H2SO4 could also
catalyze the chlorination with other chlorination reagents
(Table 2). Among all the chlorination reagents tested, H2SO4
only showed a moderate catalytic effect in accompaniment
tion conditions.
dN/A: No product or only trace product was obtained in the correspond-
ing time.
eTemperature: Room temperature.
with POCl3 (Table 2, entry 2). As a result, it was considered
that employment of the H2SO4/SOCl2 system would provide
the optimal conditions for the chlorination of carboxylic
acids, which were expanded as follows: carboxylic acid
(0.01 mol), 6 eq SOCl2, and 0.12 eq H2SO4 under reflux.
With the optimized reaction conditions in hand, to deter-
mine the substrate generality and limitations of this strategy,
numerous aromatic carboxylic acids were evaluated (Scheme
3). Generally, all the carboxylic acids in the experiments
could be converted into the corresponding acyl chloride
with high efficiency in this chlorination process regardless of
2We investigated the market prices of traditional catalysts (such as DMF,
pyridine, BTAC, TBAC, FeCl3, and FeC6H5O7) and H2SO4, and detailed
information was attached to the Supplemental Materials (see Figure S1).

4
Z. YU ET AL.
the electronic properties of the substrates, and compared straightforward and exemplified by a broad range of func-
with the results of chlorination without catalyst, the reaction tional groups tolerance in all reaction partners. The large-
rates were improved conspicuously. Firstly, some aromatic scale preparation proves that this method has potential
carboxylic acids with different electronic substituents were industrial applications. A possible dual activation mechan-
tested (Table 3, entries 1–13). With a decrease in the elec- ism was proposed to explain this catalytic process.
tron-withdrawing property of substituents, the nucleophilic-
ity of carboxylic acids increased, which led to the decrease
of reaction time. For carboxylic acids containing electron-
Acknowledgments
donating groups, the catalytic effect was not obvious because We are grateful for the Zhejiang Provincial Key R&D Project (No.
2020C03006 & 2019-ZJ-JS-03 & 2018C03074) and the National Natural
Science Foundation of China (No. 22078299).
of its high reactivity (Table 3, entries 10-13). Next, aromatic
polycarboxylic acids were investigated, under the optimized
conditions, and all the tested substrates could be converted
in high yields with prolonged reaction time (Table 3, entries
14-17). However, in the absence of a catalyst, only trace prod-
ucts could be obtained. Finally, some unstable substrates
under acidic conditions were tried (Table 3, entries 18-19).
Due to the use of H2SO4 as the catalyst, the acidity of the sys-
Declaration of competing interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influ-
ence the work reported in this paper.
tem was always in a strong state, and the ether bonds con-
tained in these carboxylic acids are unstable under acidic
ORCID
conditions.Under the optimized conditions, the ideal yields
was not obtained (45% & 37%). However, the reaction can
proceed smoothly at room temperature with excellent yields.
The screening reactions were carried out on small scale,
and encouraged by its success, the SOCl2/H2SO4 solvent/cata-
lyst system was used in a larger scale preparative reaction
(Scheme 2). The chlorination of 2,4-dichloro-5-fluorobenzoic
acid (1h) and 1a was carried out on a scale of 100 g. The reac-
tion proceeded smoothly (1h or 3a 0.5 M, H2SO4 1.2 eq,
SOCl2 4 eq, reflux) to give products in 98% and 99% conver-
sion. Then, quinolone intermediate (ethyl ꢁ2-(2,4-dichloro-5-
fluorobenzoyl)-3-(dimethylamino)acrylate, 4h) and Dinitramine
(2-methyl-3,5-dinitrobenzamide, 4a) and were obtained by sim-
ple derivatization in 93% and 96% yields respectively. These
results encouraged us that an effective and cheap strategy of
chlorination of aromatic carboxylic acids catalyzed by Brønsted
acid had been established.
Zhiqun Yu
http://orcid.org/0000-0001-5072-1509
References
[1] Hardee, D. J.; Kovalchuke, L.; Lambert, T. H. Nucleophilic Acyl
Substitution via Aromatic Cation Activation of Carboxylic
Acids: Rapid Generation of Acid Chlorides under Mild
Conditions. J. Am. Chem. Soc. 2010, 132, 5002–5003. DOI: 10.
1021/ja101292a.
[2] (a) Lin, H. K.; Dai, C. H.; Jamison, T. F.; Jensen, K. F. A Rapid
Total Synthesis of Ciprofloxacin Hydrochloride in Continuous
Flow. Angew. Chem. Int. Ed. Engl. 2017, 56, 8870–8873. DOI:
10.1002/anie.201703812. (b) Zhong, Z.; Xing, R.; Liu, S.; Wang,
L.; Cai, S.; Li, P. Synthesis of Acyl Thiourea Derivatives of
Chitosan and Their Antimicrobial Activities in Vitro.
Carbohydr. Res. 2008, 343, 566–570. DOI: 10.1016/j.carres.2007.
11.024. (c) Nitulescu, G. M.; Draghici, C.; Missir, A. V.
Synthesis of New Pyrazole Derivatives and Their Anticancer
Evaluation. Eur. J. Med. Chem. 2010, 45, 4914–4919. DOI: 10.
1016/j.ejmech.2010.07.064. (d) Chu, D. T. W.; Fernandes, P. B.;
Claiborne, A. K.; Gracey, E. H.; Pernet, A. G. Synthesis and
Structure-Activity Relationships of New Arylfluoronaphthyridine
Antibacterial Agents. J. Med. Chem. 1986, 29, 2363–2369. DOI: 10.
1021/jm00161a036. (e) Tosso, N. P.; Desai, B. K.; De Oliveira, E.;
Wen, J.; Tomlin, J.; Gupton, B. F. A Consolidated and Continuous
Synthesis of Ciprofloxacin from a Vinylogous Cyclopropyl Amide.
J. Org. Chem. 2019, 84, 3370–3376. DOI: 10.1021/acs.joc.8b03222.
(f) Fu, K.; Yang, L.; Wang, Q. F.; Zhan, F. X.; Wang, B.; Yang, Q.;
Ma, Z. J.; Zheng, G. X. A Three-Step Synthesis of Acotiamide for
the Treatment of Patients with Functional Dyspepsia. Org. Process
Res. Dev. 2015, 19, 2006–2011. DOI: 10.1021/acs.oprd.5b00256.
[3] (a) Dovlatyan, V. V.; Eliazyan, K. A.; Ghazaryan, E. A.;
Yengoyan, A. P. Synthesis of Azinylthioureas and Their
Heterocyclization Using a-Chloroacetoacetic Ester. Chem.
Heterocycl. Compd. 2006, 42, 389–391. DOI: 10.1007/s10593-
006-0097-z. (b) Frei, P.; Jones, D. H.; Kay, S. T.; McLellan, J. A.;
Johnston, B. F.; Kennedy, A. R.; Tomkinson, N. C. O.
Regioselective Reaction of Heterocyclic N-Oxides, an Acyl
Chloride, and Cyclic Thioethers. J. Org. Chem. 2018, 83,
1510–1517. DOI: 10.1021/acs.joc.7b02457.
Based on previous literature reports,[13] a possible dual acti-
vation mechanism was proposed to explain this catalytic pro-
cess (Scheme 3). Sulfonic acid was an excellent hydrogen bond
donor and hydrogen bond acceptor. The reactant complexes
(1e) were formed under the action of hydrogen bonds. In this
reactant complexes, the O-H bonds of 1a were weakened by
hydrogen bonds, which led to the increase of nucleophilicity of
oxygen atoms in 1a. Similarly, the electrophilic property of
S¼ O bonds of SOCl2 were also enhanced by hydrogen bonds.
Then, nucleophilic reactions were carried out in 1e to form
transition state 1 (1f), which forms transition state 2 (1g)
through hydrogen bonds migration, and 1g formed 2-methyl-
3,5-dinitrobenzoic sulfurochloridous anhydride (1h) after
removing the catalyst and HCl, and 1h finally formed 2a
through classical intramolecular nucleophilic reaction.
Traditional organic bases catalyzed the reaction by forming
[7]
Vilsmeier reagents with chlorination reagent
Conclusion
[4] (a) Xu, D. A Production Process of 2-Bromopropionyl
Chloride. CN patent CN104058953A, 2011. (b) Patel, D. R.;
Patel, K. C. Novel 2-Phenyl-3-f4’-[n-(4’’-aminophenyl)carba-
moyl]-phenylg-quinazoline-4(3H)one-6-sulphonic acid Based
In summary, we reported an efficient and cheap method for
chlorinating aromatic carboxylic acids. The procedure was

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
5
Mono Azo Reactive Dyes. J. Serb. Chem. Soc. 2011, 76,
177–188. DOI: 10.2298/JSC090225021P.
Cantrell, W. R.; Jenson, T. M.; Miller, S. A.; Parker, D. J.; Reel,
N. M.; Sylvester, L. G.; Szendroi, R. J.; Vargas, K. J.; Xu, J.;
et al. Efficient Large Scale Preparation of Neutral
Endopeptidase/Angiotensin-Converting Enzyme Dual Inhibitor.
Org. Process Res. Dev. 1998, 2, 238–244. DOI: 10.1021/
op970242s. (e) Pflum, D. A.; Wilkinson, H. S.; Tanoury, G. J.;
Kessler, D. W.; Kraus, H. B.; Senanayake, C. H.; Wald, S. A. A
Large-Scale Synthesis of Enantiomerically Pure Cetirizine
Dihydrochloride Using Preparative Chiral HPLC. Org. Process
Res. Dev. 2001, 5, 110–115. DOI: 10.1021/op0002951. (f) Peters,
R.; Althaus, M.; Diolez, C.; Rolland, A.; Manginot, E.; Veyrat,
M. Practical Formal Total Syntheses of the Homocamptothecin
Derivative and Anticancer Agent Diflomotecan via Asymmetric
Acetate Aldol Additions to Pyridine Ketone Substrates. J. Org.
Chem. 2006, 71, 7583–7595. DOI: 10.1021/jo060928v. (g) Iida,
T.; Satoh, H.; Maeda, K.; Yamamoto, Y.; Asakawa, K.-i.;
Sawada, N.; Wada, T.; Kadowaki, C.; Itoh, T.; Mase, T.; et al.
[5] (a) Kang, C. S.; Paik, M. J.; Park, C. W.; Baik, D. H. Synthesis
and Characterization of Polyhydroxyamide Copolymers as
Precursors of Polybenzoxazoles. Fibers Polym. 2015, 16,
239–244. DOI: 10.1007/s12221-015-0239-y. (b) Lee, E. H.; Jee,
M. H.; Kang, C. S.; Baik, D. H. Preparation and
Characterization of Polyhydroxyamide Hybrid Nanocomposite
Films Containing MWCNTs and Clay as Reinforcing Materials.
Fibers Polym. 2019, 20, 832–838. DOI: 10.1007/s12221-019-
1034-y. (c) Etxeberria, A.; Guezala, S.; Iruin, J. J.; de la Campa,
J.; de Abajo, J. Blends of Poly(Ether Imide) and an Aromatic
Poly(Ether Amide): Phase Behavior and CO2 Transport
Properties. J. Appl. Polym. Sci. 1998, 68, 2141–2149. DOI: 10.
1002/(SICI)1097-4628(19980627)68:133.0.CO;2-2.
(d)
Ben-
Haida, A.; Hodge, P.; Colquhoun, H. M. Ring-Chain
Interconversion in High-Performance Polymer Systems. 3.
Cyclodepolymerization of Poly(m-phenylene isophthalamide)
(Nomex) and Entropically Driven Ring-Opening Polymerization
of the Macrocyclic Oligomers so Produced. Macromolecules.
Practical Synthesis of
a Neuropeptide Y Antagonist via
Stereoselective Addition to a Ketene. J. Org. Chem. 2005, 70,
9222–9229. DOI: 10.1021/jo0512709.
ꢀ
2005, 38, 722–729. DOI: 10.1021/ma0401370. (e) Garcıa, J. M.;
[9] (a) Wang, L.; Xie, Y. B.; Huang, N. Y.; Yan, J. Y.; Hu, W. M.;
Liu, M. G.; Ding, M. W. Catalytic aza-Wittig Reaction of Acid
Anhydride for the Synthesis of 4H-Benzo[d][1,3]oxazin-4-ones
and 4-Benzylidene-2-aryloxazol-5(4H)-ones. Org. Lett. 2020, 22,
950–4016. DOI: 10.1021/acscatal.6b00165. (b) Zou, H.; Chen, G.
; Zhou, S. Design, Synthesis and Biological Activity Evaluation
of a New Class of 2,4-Thiazolidinedione Compounds as Insulin
Enhancers. J. Enzyme Inhib. Med. Chem. 2019, 34, 981–989.
DOI: 10.1080/14756366.2019.1608197. (c) Yu, C. G.; Matsuo, Y.
Nickel-Catalyzed Deaminative Acylation of Activated Aliphatic
Amines with Aromatic Amides via C-N Bond Activation. Org.
Lett. 2020, 22, 950–955. DOI: 10.1021/acs.orglett.9b04497. (d)
Aziz, H.; Saeed, A.; Khan, M. A.; Afridi, S.; Jabeen, F.; Ashfaq
ur, R.; Hashim, M. Novel N-Acyl-1H-imidazole-1-carbothioa-
mides: Design, Synthesis, Biological and Computational Studies.
Chem. Biodivers. 2020, 17, e1900509. DOI: 10.1002/cbdv.
201900509. (e) Jia, B.; Yang, Y.; Jin, X.; Mao, G.; Wang, C.
Rhenium-Catalyzed Phthalide Synthesis from Benzamides and
Aldehydes via C-H Bond Activation. Org. Lett. 2019, 21,
6259–6263. DOI: 10.1021/acs.orglett.9b02142. (f) Vini, R.;
Murugavel, S. Photoisomerization and Thermal Degradation
Kinetics of Poly(ether-ester)s Containing Azomethine Moiety in
the Main Chain. High Perform. Polym. 2020, 32, 47–58. DOI:
10.1177/0954008319850614. (g) Muthusamy, A.; Balaji, K.;
Murugavel, S. C.; Yuan, C.; Dai, L. Synthesis and
Characterization of Liquid Crystalline Polyesters Containing
a,b-unsaturated Ketone Moiety in the Main Chain Derived
from 2,6-bis(4-hydroxybenzylidene)cyclohexanone. Polym. Sci.
Ser. B 2020, 62, 245–255. DOI: 10.1134/s1560090420030112. (h)
Muthusamy, A.; Balaji, K.; Murugavel, S. C. Synthesis, Thermal,
and Photocrosslinking Studies of Thermotropic Liquid
ꢀ
~
Garcıa, F. C.; Serna, F.; de la Pena, J. L. High-Performance
Aromatic Polyamides. Prog. Polym. Sci. 2010, 35, 623–686.
DOI: 10.1016/j.progpolymsci.2009.09.002.
[6] (a) Zaragoza, F. One-Step Conversion of Methyl Ketones to
Acyl Chlorides. J. Org. Chem. 2015, 80, 10370–10374. DOI: 10.
1021/acs.joc.5b01707. (b) Chu, C.; Liu, R. Chloralkanes as
Chlorinating Agents: An Efficient Approach to Acyl Chlorides
and Destruction of Chlorinated Hydrocarbons. Appl. Catal. B
2011, 101, 343–347. DOI: 10.1016/j.apcatb.2010.10.002. (c) Jang,
D. O.; Park, D. J.; Kim, J. A Mild and Efficient Procedure for
the Preparation of Acid Chlorides from Carboxylic Acids.
Tetrahedron Lett. 1999, 40, 5323–5326. DOI: 10.1016/S0040-
4039(99)00967-3. (d) Zuffanti, S. Preparation of Acyl Chlorides
with Thionyl Chloride. J. Chem. Edu. 1948, 25, 481. DOI: 10.
1021/ed025p481.
[7] (a) Dunetz, J. R.; Magano, J.; Weisenburger, G. A. Large-Scale
Applications of Amide Coupling Reagents for the Synthesis of
Pharmaceuticals. Org. Process Res. Dev. 2016, 20, 140–177. DOI:
10.1021/op500305s. (b) Kimura, Y.; Matsuura, D. Novel
Synthetic Method for the Vilsmeier-Haack Reagent and Green
Routes to Acid Chlorides, Alkyl Formates, and Alkyl Chlorides.
Int. J. Org. Chem. 2013, 03, 1–7. Doi: 10.4236/ijoc.2013.33A001.
(c) Su, W. K.; Zhong, W. H.; Bian, G. F.; Shi, X. J.; Zhang, J. P.
Recent Advances in the Chemistry of Trichloromethyl
Chloroformate and Bis(trichloromethyl) Carbonate. Org. Prep.
Proced.
Int.
2004,
36,
499–547.
DOI:
10.1080/
00304940409355972. (d) Su, W. K.; Weng, Y. Y.; Zheng, C.;
Zhang, Y.; Shi, F.; Hong, B.; Chen, Z. W.; Li, J. J.; Li, Z. H.
Recent Developments in the Use of bis-(Trichloromethyl)
Carbonate in Synthesis. Org. Prep. Proced. Int. 2009, 41,
93–141. DOI: 10.1080/00304940902885839. (e) Xiao, J.; Han, L.
B. Atom-Efficient Chlorination of Benzoic Acids with PCl3
Generating Acyl Chlorides. J. Chem. Res. 2019, 43, 205–210.
DOI: 10.1177/1747519819861316.
Crystalline
Poly(benzylidene-ether)esters
Containing
a,b-Unsaturated Ketone Moiety in the Main Chain. J. Polym.
Sci. Part A: Polym. Chem. 2013, 51, 1707–1715. DOI: 10.1002/
pola.26560.
[8] (a) Wu, G.; Wong, Y.; Steinman, M.; Tormos, W.; Schumacher,
D. P.; Love, G. M.; Shutts, B. Practical Formal Total Syntheses
of the Homocamptothecin Derivative and Anticancer Agent
Diflomotecan via Asymmetric Acetate Aldol Additions to
Pyridine Ketone Substrates. J. Org. Chem. 2006, 71, 7583. DOI:
10.1021/op970105v. (b) Hoekstra, M. S.; Sobieray, D. M.;
Schwindt, M. A.; Mulhern, T. A.; Grote, T. M.; Huckabee, B. K.
; Hendrickson, V. S.; Franklin, L. C.; Granger, E. J.; Karrick, G.
L. Chemical Development of CI-1008, an Enantiomerically Pure
Anticonvulsant. Org. Process Res. Dev. 1997, 1, 26–38. DOI: 10.
1021/op9600320. (c) Dale, D. J.; Dunn, P. J.; Golightly, C.;
Hughes, M. L.; Levett, P. C.; Pearce, A. K.; Searle, P. M.; Ward,
G.; Wood, A. S. The Chemical Development of the Commercial
Route to Sildenafil: A Case History. Org. Process Res. Dev.
2000, 4, 17–22. DOI: 10.1021/op9900683. (d) Johnson, E. P.;
[10] (a) Katoono, R.; Obara, Y.; Fujiwara, K.; Suzuki, T. Enhanced
Circular Dichroism at Elevated Temperatures Through
Complexation-Induced Transformation of
a
Three-Layer
Cyclophane with Dualistic Dynamic Helicity. Chem. Sci. 2018,
9, 2222–2229. DOI: 10.1039/C7SC05242A. (b) Burdett, K. A.
An Improved Acid Chloride Preparation via Phase Transfer
Catalysis. Synthesis 1991, 1991, 441–442. DOI: 10.1055/s-1991-
ꢀ
26487. (c) Chen, G.; Lean, J. T.; Alcala, M.; Mallouk, T. E.
Modular Synthesis of p-Acceptor Cyclophanes Derived from 1,
4,5,8-Naphthalenetetracarboxylic
Diimide
and
1,5-
Dinitronaphthalene. J. Org. Chem. 2001, 66, 3027–3034. DOI:
10.1021/jo991054y.
[11] Fu, Y.; Huang, Y. Z.; Wei, L. C.; Gao, J.; Song, C.; Miao, H.;
Xu, J. Synthesis of Terephthaloyl Chloride via Acyl

6
Z. YU ET AL.
Chlorination Reaction Catalyzed by Iron Catalysts. Huaxue
Shiji 2015, 37, 152–154. DOI: 10.13822/j.cnki.hxsj.2015.02.014.
[12] Yu, Z. Q.; Xu, Q. L.; Liu, L. C.; Wu, Z. K.; Huang, J. J.; Lin,
J. Y.; Su, W. K. Dinitration of o-Toluic Acid in Continuous-
Flow: Process Optimization and Kinetic Study. J. Flow Chem.
2020, 10, 429–436. DOI: 10.1007/s41981-020-00078-6.
Catalyzed Polyurethane Formation via a Dual-Activated
Mechanism: Unexpected Preference of N-Activation over O-
Activation of Isocyanates. J. Am. Chem. Soc. 2013, 135,
16235–16241. DOI: 10.1021/ja408641g. (b) Susperregui, N.;
Delcroix, D.; Martin-Vaca, B.; Bourissou, D.; Maron, L.
Ring-Opening Polymerization of e-Caprolactone Catalyzed
by Sulfonic Acids: Computational Evidence for Bifunctional
Activation. J. Org. Chem. 2010, 75, 6581–6587. DOI: 10.
1021/jo101346t.
ꢀ
[13] (a) Sardon, H.; Engler, A. C.; Chan, J. M. W.; Garcıa, J. M.;
Coady, D. J.; Pascual, A.; Mecerreyes, D.; Jones, G. O.;
Rice, J. E.; Horn, H. W.; Hedrick, J. L. Organic Acid-