PCl3-mediated transesterification and aminolysis of tert-butyl esters via acid chloride formation

Article abstract of DOI:10.1177/1747519820987530

A PCl₃-mediated conversion of tert-butyl esters into esters and amides in one-pot under air is developed. This novel protocol is highlighted by the synthesis of skeletons of bioactive molecules and gram-scale reactions. Mechanistic studies revealed that this transformation involves the formation of an acid chloride in situ, which is followed by reactions with alcohols or amines to afford the desired products.

Full text of DOI:10.1177/1747519820987530

987530CHL0010.1177/1747519820987530Journal of Chemical ResearchWu et al.
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Journal of Chemical Research
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PCl3-mediated transesterification and aminolysis
of tert-butyl esters via acid chloride formation
https://doi.org/10.1177/1747519820987530
DOI: 10.1177/1747519820987530
journals.sagepub.com/home/chl
Xiaofang Wu, Lei Zhou, Fangshao Li and Jing Xiao
Abstract
A PCl3-mediated conversion of tert-butyl esters into esters and amides in one-pot under air is developed. This novel
protocol is highlighted by the synthesis of skeletons of bioactive molecules and gram-scale reactions. Mechanistic studies
revealed that this transformation involves the formation of an acid chloride in situ, which is followed by reactions with
alcohols or amines to afford the desired products.
Keywords
acid chlorides, amides, esters, phosphorus trichloride, tert-butyl esters
Date received: 30 October 2020; accepted: 22 December 2020
O
1OH
R
R
R
OR1
O
O
PCl3
R
O
R
Cl
O
R2R3NH
NR2R3
R, R1, R2, R3 = Aryl, Alkyl, Alkenyl, H, etc.
chlorine atoms. The need for esters and amides in our ongo-
ing research encouraged us to investigate methods for their
synthesis. To the best of our knowledge, there has been no
report on the reaction of PCl3 with esters that provides the
corresponding acid chlorides for further reactions, albeit
there are a few examples of the conversion of tert-butyl
esters into acid chlorides having been reported, some of
them using a large excess of chlorinating reagents.29 Herein,
we report an efficient PCl3-mediated transesterification and
aminolysis of esters, providing the corresponding esters
and amides in good-to-high yields (Scheme 1). Notably,
when a large-scale reaction was conducted, only 2/3 equiv.
of PCl3 was required.
Introduction
Ester and amide functionalities are ubiquitous in pharma-
ceuticals, natural products, agriculture, functional materi-
als, and synthetic organic chemistry.1–7 Traditional methods
for the preparation of esters and amides involve the reac-
tions of carboxylic acids with alcohols or amines.5,6
However, these methods suffer from dry reaction condi-
tions and the generation of toxic wastes. In recent years, the
transesterification and aminolysis of esters have repre-
sented alternative routes for the synthesis of various esters
and amides.8–11 However, transesterification and aminoly-
sis of esters usually require the use of transition-metal cata-
lysts such as Pd,12,13 Co,14 Ru,15,16 and Au,17 excess of
bases,18,19 metal alkoxides,10,20 carbenes,21–23 and so on,24–28
which are limited by high costs, low availability, and harsh
reaction conditions. Moreover, there are only a few exam-
ples involving the transesterification and aminolysis of
esters using the same system. Thus, the development of an
efficient, low-cost, and environmentally friendly methodol-
ogy for the synthesis of esters and amides is in high demand.
Phosphorus trichloride (PCl3) is a cheap and readily
available industrial chemical. Recently, we became
intrigued by the fact that PCl3 may serve as a green chlorin-
ating reagent due to one molecule of PCl3 having three
Key Laboratory of Theoretical Organic Chemistry and Functional
Molecule of Ministry of Education, School of Chemistry and Chemical
Engineering, Hunan University of Science and Technology, Xiangtan, P.R.
China
Corresponding author:
Jing Xiao, Key Laboratory of Theoretical Organic Chemistry and
Functional Molecule of Ministry of Education, School of Chemistry and
Chemical Engineering, Hunan University of Science and Technology,
Hunan Xiangtan Taoyuan Road, Xiangtan 411201, P.R. China.
Email: XiaoJing@hnust.edu.cn
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Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use,
reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and
Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).

2
Journal of Chemical Research 00(0)
Table 2. Substrate scope with various tert-butyl esters.a
O
O
1OH
R
O
O
(a)
(b)
R
R
OR1
1) PCl3
O
O
R
O
R
OMe
PCl3
2) MeOH
1
2
R
O
R
Cl
R2R3NH
O
O
O
O
NR2R3
R, R1, R2, R3 = Aryl, Alkyl, Alkenyl, H, etc.
OMe
OMe
OMe
MeO
OMe
OMe
Me
b
2a:
2e:
2b: 72%
2c:
2g:
2d:
2h:
86%
O
83%
81%
O
Scheme 1. PCl3-mediated transesterification and aminolysis of
tert-butyl esters.
O
O
OMe
OMe
F3C
OMe
F
Cl
Ac
c
85%
O
2f:
64%
94%
93%
Table 1. Optimization of the reaction conditions.a
O
OMe
OMe
OMe
OMe
OMe
O
O
O
O
O
O
OMe
O
c
1) PCl3
b
2i:
63%
OMe
2j: 90%
2k:
2o:
70%
2l:
96%
O
MeOH
2)
OMe
1a
Conditions
2a
OMe
O
d
2n: 95%
2m:
2p:
95%
96%
94%
Entry
Yield (%)b
aConditions: (1) 1 (1.3mmol), PCl3 (1.3mmol), and CH3CN (2.0mL)
were stirred in a sealed 25-mL Schlenk tube at 80°C for 3h under air
and (2) MeOH (5.0equiv.) was added and the mixture was stirred at
80°C for 2h. Yield of isolated products are given.
1
2
3
4
5
6
sealed tube, N2
sealed tube, air
sealed tube, air
sealed tube, air
sealed tube, 60°C, air
sealed tube, 2/3 equiv. of PCl3, air
83
92
44c
92d
87
bStep (1) was performed at 60°C for 6h and step (2) was performed at
60°C for 2h.
cSteps (1) and (2) were performed at 100°C for 3 and 2h, respectively.
dSteps (1) and (2) were performed at 60°C for 3 and 2h, respectively.
78
aConditions: (1) 1a (0.3mmol), PCl3 (0.3mmol), and CH3CN (0.6mL)
were stirred at 80°C for 3h under air and (2) MeOH (5.0equiv.) was
added and the mixture was stirred at 80°C for 2h.
bGC yield based on 1a using dodecane as an internal standard.
cMeOH (3.0equiv.) was used.
Table 3. Substrate scope with different alcohols.a
O
O
1) PCl3
OR1
dMeOH (6.0equiv.) was used.
O
R1OH
2)
The bold in Table 1 means the optimal reaction condition.
1a
2
O
O
O
O
Results and discussion
O
O
We initiated our research on the transesterification of tert-
butyl benzoate. As demonstrated in Table 1, tert-butyl benzo-
ate (1a) and PCl3 (1.0 equiv.) were stirred in CH3CN at 80°C
for 3h, then MeOH (5.0 equiv.) was added under N2 to afford
methyl benzoate (2a) in 83% yield (entry 1). Similarly, when
the reaction was conducted in air, the product was generated in
92% yield (entry 2). Further reducing or increasing the amount
of MeOH did not improve the reaction efficiency (entries 3
and 4). An 87% yield of the product was generated when the
reaction temperature was lowered to 60°C (entry 5). To our
delight, when 2/3 equiv. of PCl3 was used, a 78% yield of
methyl benzoate was obtained (entry 6). We also examined the
reactivity of methyl, isopropyl, and phenyl benzoate in this
reaction. However, no product was detected by gas chroma-
tography–mass spectrometry (GC-MS).
Next, the generality of this transesterification was
explored. We were pleased to find that the reaction of vari-
ous tert-butyl esters with MeOH proceeded efficiently in
one-pot to give the corresponding products in good to
excellent yields. As shown in Table 2, both electron-rich
and electron-deficient substrates provided the correspond-
ing aryl esters (2a–h) under the optimized reaction condi-
tions in good to excellent yields. A vinyl group at the para
position was tolerated well (2i) and tert-butyl 2-naphthoate
underwent this reaction smoothly to give 2j in 90% yield.
2q:
2r:
2s:
87%
96%
84%
O
O
O
O
2t:
2u:
81%
52%
aConditions: (1) 1a (1.3mmol), PCl3 (1.3mmol), and CH3CN (2.0mL)
were stirred in a sealed tube at 80°C for 3h under air and (2) R1OH
(6.0 equiv.) was added and the mixture was stirred at 80°C for 11h.
Yield of isolated products are given.
Moreover, benzyl esters such as tert-butyl 2-(naphthalen-
2-yl)acetate, tert-butyl 2-(p-tolyl)acetate, and tert-butyl
2-phenylpropanoate were also found to be suitable sub-
strates (2k–m). The alkenyl ester tert-butyl cinnamate
reacted readily to afford methyl cinnamate (2n) in 95%
yield. It should be noted that alkyl esters, such as tert-butyl
3-phenylpropanoate and tert-butyl hexanoate, exhibited
good reactivity, furnishing the expected products 2o and 2p
in 96% and 94% yield, respectively.
We next explored the reaction of tert-butyl benzoate
with different alcohols under similar conditions (Table 3).
Gratifyingly, by prolonging the reaction time to 11h, etha-
nol and isopropanol were amenable to this transesterifica-
tion and the expected products 2q and 2r were obtained in

Wu et al.
3
good to excellent yields. Notably, when sterically hindered Moreover, secondary amines, such as N-methylaniline and
alcohols, such as cyclohexanol and phenol, were subjected diphenylamine, were also successfully employed to give
to the reaction, 87% and 81% yields of the products 2s and the amide products 3d and 3e in 83% and 82% yields,
2t were achieved, respectively. Benzyl alcohol provided the respectively. To our delight, this aminolysis reaction could
corresponding product 2u in a modest yield.
also be extended to aliphatic amines and aliphatic tert-butyl
We subsequently investigated if this PCl3-mediated sys- esters giving products 3f–j.
tem could be applicable for the aminolysis of tert-butyl
Reactions to synthesize valuable skeletons of bioactive
esters (Table 4). For primary amines, such as aniline, molecules were conducted to demonstrate the potential
4-fluoroaniline, and 4-methoxyaniline, moderate-to-good synthetic utility of this aminolysis reaction (Scheme 2).
yields of the amidated products 3a–c were obtained. Thus, dimethylamine and morpholine were subjected to
this reaction to afford the corresponding skeletons of bioac-
tive molecules30–32 in 77% and 75% yields, respectively
(equations (1) and (2)). Interestingly, benzenesulfonamide
Table 4. PCl3-mediated aminolysis of tert-butyl esters.a
could also be converted into the product 3m, which is the
O
O
1) PCl3
2) R2R3NH
NR2R3
scaffold of the biologically active compound cyprosulfa-
R
O
R
O
mide (equation (3)).33
1a
3
The value of this PCl3-mediated system lies further on
the scalability of the reaction. As depicted in Scheme 3,
gram-scale reactions were conducted on 10-mmol scale
with a reduced quantity of PCl3 usage (2/3equiv.) and the
desired products, such as methyl benzoate and N,N-
dibutylbenzamide, were obtained in 81% and 90% yields,
respectively. As one molecule of PCl3 has three chlorine
atoms which can be utilized in the reaction, this may
account for the lower PCl3 loading.34
A series of control experiments have been carried out to
probe the mechanism (Scheme 4). A 93% yield of benzoyl
chloride was generated when 1a and PCl3 were stirred in
CH3CN at 80°C for 3h under air (equation (4)). This result
indicated that acid chlorides are the key intermediates
which react with alcohols and amines to afford the prod-
ucts. To study the formation of acid chlorides from esters,
1.5equiv. of HCl instead of PCl3 were subjected to the reac-
tion and a 90% yield of benzoic acid and 8% of 2a were
F
OMe
O
O
O
N
H
N
H
N
H
N
3a: 76%
3b: 85%
3c: 71%
3d: 83%
O
O
O
N
N
H
N
3e: 82%b
3f: 70%c
3g: 90%c
H
N
O
O
N
N
H
O
H
3h: 90%c,d
3i: 89%c,d
3j: 48%e
aConditions: (1) 1a (1.3mmol), PCl3 (1.3mmol), and CH3CN (2.0mL)
were stirred in a sealed tube at 80°C for 3h under air and (2) R2R3NH
(1.0equiv.) was added and the mixture stirred at 80°C for 2h. Isolated
yields.
bStep (2) was performed at 100°C for 2h.
cAmine (3.0equiv.) was used.
dSteps (1) and (2) were performed at 60°C for 6 and 2h, respectively.
eStep (2) was performed at 80°C for 0.5h.
O
O
O
O
n-Pr
t-Bu
N
O
N
O
(1)
3k: 77%
Histone deacetylase inhibitor
O
O
O
HO
N
t-Bu
N
O
(2)
O
O
MeO
3l:
75%
Antitumor agent
OMe
O
O
O
O
t-Bu
O
O
O
S
N
(3)
HN
S
O
H
MeO
NH
O
MeO
3m:
81%
Cyprosulfamide
Conditions: ester
CN (2.0 mL) were stirred in a sealed tube at
(1.0 mmol), PCl3 (1.0 mmol) and CH3
80 oC for 3 hours under air; (2) The amines (6.0 equiv) or sulfamide (1.0 equiv) were added and the
mixture stirred at 80 oC for another 11 hours.
Scheme 2. The synthesis of skeletons of bioactive molecules.

4
Journal of Chemical Research 00(0)
obtained, respectively (equations (5) and (6)). The reaction can react with PCl3 or the P-Cl reagent to afford acid chlo-
was suppressed in the presence of 2.0equiv. of pyridine rides.34 Thus, there are two roles played by PCl3 in this
(equation (7)). We attribute the trace yield of 2a to the neu- reaction: formation of HCl in situ and the chloride reagent.
tralization of HCl which was easily formed by the reaction
Based on the above results and our previous reports,29,34
of PCl3 with water in air or in the solvent. These results a possible mechanism has been proposed. As shown in
indicate that HCl generated in situ plays an important role Scheme 5, we considered two processes for this reaction.
in the reaction. As we reported previously, benzoic acids The first involves hydrolysis of ester 1 to give the corre-
sponding acid 5 with the aid of HCl. Subsequent reaction of
acid 5 with (OH)nPCl3-n (n=0, 1, 2), then forms the corre-
O
O
sponding acyl chlorides 4. The second is the complexation
of 1 with 6 followed by the elimination of a tert-butyl cat-
ion to afford chlorides 7. The resulting intermediate 7 then
reacts with HCl to afford 4. The reaction of 4 with the alco-
hol or amine provides the product 2 or 3, respectively.
1) PCl3 (2/3 equiv)
MeOH
OMe
O
2)
(5.0 equiv)
1a
2a:
3g:
81% (1.103 g)
O
O
1) PCl3 (2/3 equiv)
(n-Bu) NH
O
2)
(3.0 equiv)
2
N
1a
Conclusion
90% (2.100 g)
In summary, using cheap and readily available PCl3, an
efficient transesterification and aminolysis of tert-butyl
esters has successfully been demonstrated. Mechanistic
studies revealed that the reaction proceeds via an acid chlo-
ride. This new method provides an efficient and simple pro-
tocol to synthesize a wide range of esters and amides from
tert-butyl esters. Furthermore, this approach has been
applied to the synthesis of the frameworks of bioactive
molecules and is easily scaled up even when 2/3equiv. of
PCl3 are used.
Scheme 3. Scale-up reactions.
O
O
PCl3 (1.0 equiv.)
CH3CN (0.6 mL), 80 o
O
Cl
(4)
(5)
C, 3 h, air
4a:
93%
O
1a
O
HCl (1.5 equiv.)
CH3CN (0.6 mL), 80 o
O
O
O
OH
C, 3 h, air
Experimental
1a
5a:
2a:
2a:
90%
O
O
Unless otherwise noted, all reactions were carried out in
sealed oven-dried Schlenk tubes under air. Reagents and
solvents were obtained from commercial suppliers and
used without purification. Flash column chromatography
was performed using 200–300 mesh silica gel. Visualization
on thin-layer chromatography (TLC) was achieved by the
use of UV light (254nm). A FULI GC-9790II equipped
with a flame ionization detector (FID) detector was used to
1) HCl (1.5 equiv.)
OMe
(6)
(7)
2) MeOH (5.0 equiv.)
1a
O
8%
O
1) PCl3 (1.0 equiv.);
Pyridine (2.0 equiv.)
OMe
2) MeOH (5.0 equiv.)
1a
trace
1
analysis the reaction mixture. H nuclear magnetic reso-
nance (NMR) and 13C NMR spectra were recorded on a
Scheme 4. Control experiments.
PCl3
(OH)nPCl3-n
6
H
2O
HCl
(n = 0, 1, 2)
OH
6
O
+
O
R1
OH
R
OH
R
O
R
OR1
(a)
5
O
2
1
R
Cl
4
n
n
(OH)
P
(OH)
P
O
6
R2
+
R2R3NH
Cl2-n
O
Cl2-n
O
R
N
HCl
(b)
3
R3
R
O
R
O
7
Scheme 5. Possible mechanisms.

Wu et al.
5
Bruker AV-II 500-MHz NMR spectrometer (1H: 500MHz,
Methyl 4-(trifluoromethyl)benzoate (2g):40 Light yellow
13C: 125.76MHz) in CDCl3 or DMSO-d6. The coupling oil; yield: 93% (246.6mg). Eluent: petroleum ether/
1
1
constants J are given in Hz. Chemical shifts for H NMR EtOAc=10/1. H NMR (500MHz CDCl3): δ 8.07 (d,
are referred to internal Me4Si (0ppm). GC-MS was recorded J=8.0Hz, 2H), 7.63 (d, J=8.5Hz, 2H), 3.88 (s, 3H). 13C
on a Shimadzu GCMS-QP2010 plus equipped with an elec- NMR (125.76MHz, CDCl3): δ 165.4, 133.9 (q, JC-
tron ionization (EI) ion source. Substrates 1c,35 1d,36 1f,37 F =32.7Hz), 132.9, 129.5, 124.9 (q, JC-F =3.1Hz), 123.1 (q,
1g,38 1h–m,39 1n,37 1o,39 and 1p36 were synthesized accord- JC-F =272.8Hz), 52.0. GC-MS (EI, 70eV): m/z=204 (M+).
ing to the known methods.
Methyl 4-acetylbenzoate (2h):43 White solid; yield: 64%
Typical procedure for the preparation of the target mol- (148.1mg). Eluent: petroleum ether/EtOAc=10/1. 1H
ecules: Under air, tert-butyl ester 1 (1.3 or 0.3mmol), PCl3 NMR (500MHz CDCl3): δ 8.06 (d, J=8.5Hz, 2H), 7.94 (d,
(1.0equiv.), and CH3CN (0.6mL) were added to a 25-mL J=8.5Hz, 2H), 3.88 (s, 3H), 2.58 (s, 3H). 13C NMR
sealed Schlenk tube equipped with a magnetic stir bar. The (125.76MHz, CDCl3): δ 197.1, 165.8, 139.7, 133.4, 129.4,
mixture was stirred at 80°C for 3h. Next, the correspond- 127.7, 52.0, 26.4. GC-MS (EI, 70eV): m/z=178 (M+).
ing alcohol (5.0equiv.) or amine (1.0 or 3.0equiv.) was
Methyl 4-vinylbenzoate (2i):44 White solid; yield: 63%
added to the reaction and the mixture was stirred at the indi- (132.7mg). Eluent: petroleum ether/EtOAc=10/1. 1H
cated temperature for the indicated amount of time. The NMR (500MHz CDCl3): δ 7.92 (d, J=8.5Hz, 2H), 7.38 (d,
mixture was then quenched with aqueous NaHCO3 solution J=8.5Hz, 2H), 6.70–6.64 (m, 1H), 5.79 (d, J=17.5Hz,
and extracted with EtOAc (×3). The combined organic 1H), 5.30 (d, J=11.0Hz, 1H), 3.83 (s, 3H). 13C NMR
layer was dried over MgSO4 and filtered. After evaporation (125.76MHz, CDCl3): δ 166.4, 141.4, 135.5, 129.4, 128.8,
of the solvent under reduced pressure, the residue was puri- 125.6, 116.0, 51.6. GC-MS (EI, 70eV): m/z=162 (M+).
fied by column chromatography on silica gel to give the
analytically pure product 2 or 3.
Methyl 2-naphthoate (2j):40 Light yellow solid; yield:
90% (217.6mg). Eluent: petroleum ether/EtOAc=10/1. 1H
Methyl benzoate (2a):40 Colorless oil; yield: 86% NMR (500MHz CDCl3): δ 8.54 (s, 1H), 7.89 (dd, J=1.5Hz,
(152.1mg). Petroleum ether/EtOAc=10/1. 1H NMR 8.5Hz, 1H), 7.89 (d, J=8.0Hz, 1H), 7.81 (d, J=8.5Hz,
(500MHz, CDCl3): δ 8.07–8.05 (m, 2H), 7.59–7.56 (m, 1H), 2H), 7.54–7.46 (m, 2H), 3.91 (s, 3H). 13C NMR
7.47–7.44 (m, 2H), 3.93 (s, 3H). 13C NMR (125.76MHz (125.76MHz, CDCl3): δ 167.3, 135.5, 132.5, 131.1, 129.4,
CDCl3): δ 167.2, 133.0, 130.1, 129.6, 128.4, 52.2. GC-MS 128.3, 128.2, 127.8, 127.4, 126.7, 125.2, 52.3. GC-MS (EI,
(EI, 70eV): m/z=136 (M+).
70eV): m/z=186 (M+).
Methyl 4-methylbenzoate (2b):40 Colorless oil; yield:
Methyl 2-(naphthalen-2-yl)acetate (2k):45 White solid;
72% (140.5mg). Eluent: petroleum ether/EtOAc=10/1. 1H yield: 70% (182.0mg). Eluent: petroleum ether/
NMR (500MHz CDCl3): δ 7.84 (d, J=8.0Hz, 2H), 7.14 (d, EtOAc=10/1. 1H NMR (500MHz CDCl3): δ 7.74–7.01 (m,
J=8.0Hz, 2H), 3.80 (s, 3H), 2.31 (s, 3H). 13C NMR 3H), 7.65 (s, 1H), 7.41–7.32 (m, 3H), 3.71 (s, 2H), 3.62 (s,
(125.76MHz, CDCl3): δ 167.2, 143.6, 129.6, 129.1, 127.4, 3H). 13C NMR (125.76MHz, CDCl3): δ 172.1, 133.5,
51.9, 21.6. GC-MS (EI, 70eV): m/z=150 (M+).
132.5, 131.5, 128.3, 128.0, 127.7, 127.7, 127.4, 126.2,
Methyl 2,4,6-trimethylbenzoate (2c):41 Colorless oil; 125.9, 52.2, 41.4. GC-MS (EI, 70eV): m/z=200 (M+).
yield: 83% (192.1mg). Eluent: petroleum ether/
Methyl 2-(p-tolyl)acetate (2l):46 Colorless oil; yield:
EtOAc=10/1. 1H NMR (500MHz CDCl3): δ 6.66 (s, 2H), 96% (204.7mg). Eluent: petroleum ether/EtOAc=10/1. 1H
3.70 (s, 3H), 2.11 (s, 6H), 2.09 (s, 3H). 13C NMR NMR (500MHz CDCl3): δ 7.07–7.02 (m, 4H), 3.57 (s, 3H),
(125.76MHz, CDCl3): δ 170.6, 139.3, 135.2, 130.9, 128.4, 3.48 (s, 2H), 2.22 (s, 3H). 13C NMR (125.76MHz, CDCl3):
51.7, 21.1, 19.8. GC-MS (EI, 70eV): m/z=178 (M+).
δ 171.8, 136.3, 130.5, 128.9, 128.7, 51.6, 40.3, 20.6.
Methyl 4-methoxybenzoate (2d):40 White solid; yield: GC-MS (EI, 70eV): m/z=164 (M+).
81% (174.8mg). Eluent: petroleum ether/EtOAc=10/1. 1H
Methyl 2-phenylpropanoate (2m):47 Light yellow oil;
NMR (500MHz CDCl3): δ 7.93–7.90 (m, 2H), 6.86–6.83 yield: 95% (202.5mg). Eluent: petroleum ether/
(m, 2H), 3.81 (s, 3H), 3.78 (s, 3H). 13C NMR (125.76MHz, EtOAc=10/1. 1H NMR (500MHz CDCl3): δ 7.39–7.34 (m,
CDCl3): δ 166.9, 163.3, 131.6, 122.6, 113.6, 55.4, 51.9. 4H), 7.31–7.28 (m, 1H), 3.78 (q, J=7.0Hz, 1H), 3.69 (s,
GC-MS (EI, 70eV): m/z=166 (M+).
3H), 1.55 (d, J=7.0Hz, 3H). 13C NMR (125.76MHz,
Methyl 4-fluorobenzoate (2e):42 Colorless oil; yield: CDCl3): δ 174.5, 140.1, 128.2, 127.0, 126.7, 51.6, 45.0,
85% (170.2mg). Eluent: petroleum ether/EtOAc=10/1. 1H 18.2. GC-MS (EI, 70eV): m/z=164 (M+).
NMR (500MHz CDCl3): δ 8.02–8.00 (m, 2H), 7.08–7.04
Methyl cinnamate (2n):42 Light yellow solid; yield: 95%
(m, 2H), 3.87 (s, 3H). 13C NMR (125.76MHz, CDCl3): δ (200.1mg). Eluent: petroleum ether/EtOAc=10/1. 1H
165.5, 165.2 (d, JC-F =252.2Hz), 131.6 (d, JC-F =9.3Hz), NMR (500MHz CDCl3): δ 7.63 (d, J=16.0Hz, 1H), 7.47–
125.9 (d, JC-F =2.6Hz), 114.9 (d, JC-F =21.9Hz), 51.6. 7.45 (m, 2H), 7.33–7.30 (m, 3H), 6.38 (d, J=16.0Hz, 1H),
GC-MS (EI, 70eV): m/z=154 (M+).
3.74 (s, 3H). 13C NMR (125.76MHz, CDCl3): δ 167.5,
Methyl 4-chlorobenzoate (2f):40 White solid; yield: 94% 144.9, 134.4, 130.3, 128.9, 128.1, 117.8, 51.7. GC-MS (EI,
(207.7mg). Eluent: petroleum ether/EtOAc=10/1. 1H 70eV): m/z=162 (M+).
NMR (500MHz CDCl3): δ 7.90 (d, J=8.5Hz, 2H), 7.34 (d,
Methyl 3-phenylpropanoate (2o):48 Light yellow oil;
J=8.5Hz, 2H), 3.84 (s, 3H). 13C NMR (125.76MHz, yield: 96% (204.7mg). Eluent: petroleum ether/
CDCl3): δ 165.8, 138.9, 130.5, 128.2, 128.1, 51.8. GC-MS EtOAc=10/1. 1H NMR (500MHz CDCl3): δ 7.19–7.16 (m,
(EI, 70eV): m/z=170 (M+).
2H), 7.11–7.08 (m, 3H), 3.55 (s, 3H), 2.85 (t, J=7.5Hz,

6
Journal of Chemical Research 00(0)
2H), 2.52 (t, J=8.0Hz, 2H). 13C NMR (125.76MHz, 128.1, 122.7, 115.6 (d, JC-F =22.6Hz). GC-MS (EI, 70eV):
CDCl3): δ 172.9, 140.2, 128.1, 127.8, 125.8, 51.2, 35.3, m/z=215 (M+).
30.5. GC-MS (EI, 70eV): m/z=164 (M+).
(4-Methoxyphenyl)benzamide (3c):50 Light yellow solid;
Methyl hexanoate (2p):40 Colorless oil; yield: 94% yield: 71% (209.5mg). Eluent: petroleum ether/
1
(158.9mg). Eluent: petroleum ether. H NMR (500MHz EtOAc=5/1. 1H NMR (500MHz CDCl3): δ 7.79 (d,
CDCl3): δ 3.60 (s, 3H), 2.23 (t, J=7.5Hz, 2H), 1.59–1.53 J=7.5Hz, 2H), 7.73 (brs, 1H), 7.48–7.45 (m, 3H), 7.42–
(m, 2H), 1.27–1.22 (m, 4H), 0.83 (t, J=7.0Hz, 3H). 13C 7.39 (m, 2H), 6.85–6.82 (m, 2H), 3.74 (s, 3H). 13C NMR
NMR (125.76MHz, CDCl3): δ 174.3, 51.4, 34.1, 31.3, (125.76MHz, CDCl3): δ 165.7, 156.7, 135.0, 131.7, 131.0,
24.6, 22.3, 13.9. GC-MS (EI, 70eV): m/z=130 (M+).
128.8, 127.0, 122.1, 114.3, 55.5. GC-MS (EI, 70eV):
Ethyl benzoate (2q):47 Light yellow oil, yield 96% m/z=227 (M+).
(187.2mg). Eluent: petroleum ether/EtOAc=10/1. 1H
N-Methyl-N-phenylbenzamide (3d):50 Light yellow oil;
NMR (500MHz CDCl3): δ 7.99–7.97 (m, 2H), 7.50–7.46 yield: 83% (227.7mg). Eluent: petroleum ether/
(m, 1H), 7.38–7.35 (m, 2H), 4.31 (q, J=7.5Hz, 2H), 1.33 EtOAc=5/1. 1H NMR (500MHz CDCl3): δ 7.22–7.21 (m,
(t, J=7.0Hz, 3H); 13C NMR (125.76MHz, CDCl3): δ 2H), 7.17–7.13 (m, 3H), 7.09–7.04 (m, 3H), 6.95 (d,
166.7, 132.8, 130.5, 129.5, 128.3, 61.0, 14.4. GC-MS (EI, J=7.5Hz, 2H), 3.42 (s, 3H). 13C NMR (125.76MHz,
70eV): m/z=150 (M+).
CDCl3): δ 170.7, 144.9, 135.9, 129.6, 129.2, 128.7, 127.7,
Isopropyl benzoate (2r):47 Light yellow oil; yield: 84% 126.9, 126.5, 38.4. GC-MS (EI, 70eV): m/z=211 (M+).
(179.1mg). Eluent: petroleum ether/EtOAc=10/1. 1H N,N-Diphenylbenzamide (3e):50 White solid; yield: 82%
NMR (500MHz CDCl3): δ 7.94–7.95 (m, 2H), 7.47–7.44 (291.1mg). Eluent: petroleum ether/EtOAc=5/1. 1H NMR
(m, 1H), 7.36–7.33 (m, 2H), 5.21–5.14 (m, 1H), 1.29 (d, (500MHz CDCl3): δ 7.39–7.38 (m, 2H), 7.23–7.20 (m,
J=6.5Hz, 6H). 13C NMR (125.76MHz, CDCl3): δ 166.1, 5H), 7.16–7.08 (m, 8H). 13C NMR (125.76MHz, CDCl3): δ
132.7, 130.9, 129.5, 128.3, 68.4, 22.0. GC-MS (EI, 70eV): 170.8, 143.9, 136.1, 130.2, 129.2, 129.1, 127.9, 127.5,
m/z=164 (M+).
126.4. GC-MS (EI, 70eV): m/z=273 (M+).
Cyclohexyl benzoate (2s):49 Light yellow oil; yield: 87%
Benzylbenzamide (3f):50 White solid, yield 70%
(230.7mg). Eluent: petroleum ether/EtOAc=10/1. 1H (192.0mg). Eluent: petroleum ether/EtOAc=5/1. 1H NMR
NMR (500MHz CDCl3): δ 7.98–7.96 (m, 2H), 7.46–7.43 (500MHz CDCl3): δ 7.73–7.71 (m, 2H), 7.45–7.42 (m,
(m, 1H), 7.35–7.32 (m, 2H), 4.97–4.92 (m, 1H), 1.87–1.84 1H), 7.38–7.34 (m, 2H), 7.29–7.21 (m, 5H), 6.36 (brs, 1H),
(m, 2H), 1.71–1.69 (m, 2H), 1.52–1.47 (m, 3H), 1.40–1.24 4.58 (d, J=5.5Hz, 2H). 13C NMR (125.76MHz, CDCl3): δ
(m, 3H). 13C NMR (125.76MHz, CDCl3): δ 166.0, 132.7, 167.4, 138.2, 134.4, 131.6, 128.8, 128.6, 128.0, 127.7,
131.0, 126.5, 128.3, 73.0, 31.7, 25.5, 23.7. GC-MS (EI, 127.0, 44.2. GC-MS (EI, 70eV): m/z=211 (M+).
70eV): m/z=204 (M+).
N,N-Dibutylbenzamide (3g):52 Light yellow oil; yield:
Phenyl benzoate (2t):47 White solid; yield: 81% 90% (272.6mg). Eluent: petroleum ether/EtOAc=5/1. H
(208.5mg). Eluent: petroleum ether/EtOAc=10/1. 1H NMR (500MHz CDCl3): δ 7.30–7.25 (m, 5H), 3.41–3.10
NMR (500MHz CDCl3): δ 8.15–8.13 (m, 2H), 7.58–7.55 (m, 4H), 1.57–1.32 (m, 6H), 1.04–0.70 (m, 8H). 13C NMR
(m, 1H), 7.46–7.42 (m, 2H), 7.38–7.34 (m, 2H), 7.22–7.17 (125.76MHz, CDCl3): δ 171.6, 137.4, 129.0, 128.3, 126.4,
(m, 1H), 7.15–7.13 (m, 2H). 13C NMR (125.76MHz, 48.7, 44.4, 30.8, 29.6, 20.3, 19.7, 13.9, 13.6. GC-MS (EI,
CDCl3): δ 165.2, 151.0, 133.6, 130.2, 129.6, 129.5, 128.6, 70eV): m/z=233 (M+).
1
125.9, 121.8. GC-MS (EI, 70eV): m/z=198 (M+).
N-Phenyl-2-(p-tolyl)acetamide (3h):53 White solid;
Benzyl benzoate (2u):40 Colorless oil; yield: 52% yield: 90% (263.3mg). Eluent: petroleum ether/
(143.3mg). Eluent: petroleum ether/EtOAc=10/1. 1H EtOAc=5/1. 1H NMR (500MHz CDCl3): δ 7.34–7.33 (m,
NMR (500MHz CDCl3): δ 8.17–8.15 (m, 2H), 7.62–7.59 2H), 7.20–7.17 (m, 3H), 7.14–7.10 (m, 4H), 7.01–6.98 (m,
(m, 1H), 7.53–7.44 (m, 6H), 7.42–7.39 (m, 1H), 5.44 (s, 1H), 3.61 (s, 2H), 2.29 (s, 3H). 13C NMR (125.76MHz,
2H). 13C NMR (125.76MHz, CDCl3): δ 166.5, 136.1, CDCl3): δ 169.51, 137.68, 137.43, 131.33, 129.95, 129.46,
133.1, 130.2, 129.8, 128.7, 128.5, 128.3, 128.3, 66.8. 128.93, 124.44, 119.87, 44.41, 21.15. GC-MS (EI, 70eV):
GC-MS (EI, 70eV): m/z=212 (M+).
m/z=225 (M+).
N-phenylbenzamide (3a):50 White solid; yield: 76%
N,3-Diphenylpropanamide (3i):53 White solid; yield:
1
1
(194.6mg). Eluent: petroleum ether/EtOAc=5/1. H NMR 89% (260.3mg). Eluent: petroleum ether/EtOAc=5/1. H
(500MHz CDCl3): δ 7.81–7.78 (m, 3H), 7.58–7.57 (m, 2H), NMR (500MHz CDCl3): δ 7.75–7.70 (m, 1H), 7.35–7.33
7.50–7.47 (m, 1H), 7.44–7.41 (m, 2H), 7.31 (t, J=8.0Hz, (m, 2H), 7.17–7.06 (m, 7H), 6.98–6.95 (m, 1H), 2.90 (t,
2H), 7.09 (t, J=7.5Hz, 1H). 13C NMR (125.76MHz, J=8.0Hz, 2H), 2.52 (t, J=8.0Hz, 2H). 13C NMR
CDCl3): δ 165.8, 137.9, 135.0, 131.9, 129.1, 128.8, 127.0, (125.76MHz, CDCl3): δ 171.02, 140.66, 137.89, 128.96,
124.6, 120.2. GC-MS (EI, 70eV): m/z=197 (M+).
128.65, 128.41, 126.38, 124.39, 120.30, 39.25, 31.64.
N-(4-Fluorophenyl)benzamide (3b):51 White solid; GC-MS (EI, 70eV): m/z=225 (M+).
yield: 85% (237.6mg). Eluent: petroleum ether/
N-Phenylhexanamide (3j):54 White solid; yield: 48%
1
1
EtOAc=5/1. H NMR (500MHz DMSO-d6) δ 10.30 (s, (119.2mg). Eluent: petroleum ether/EtOAc=5/1. H NMR
1H), 7.97–7.94 (m, 2H), 7.82–7.78 (m, 2H), 7.61–7.57 (500MHz CDCl3): δ 7.53–7.51 (m, 2H), 7.38 (brs, 1H),
(m, 1H), 7.55–7.51 (m, 2H), 7.22–7.17 (m, 2H). 13C NMR 7.30 (t, J=8.0Hz, 2H), 7.11–7.08 (m, 1H), 2.35 (t, J=7.5Hz,
(125.76MHz, DMSO-d6) δ 165.9, 158.8 (d, JC-F
=
2H), 1.75–1.69 (m, 2H), 1.38–1.33 (m, 4H), 0.90 (t,
240.2Hz) 136.0 (d, JC-F =2.5Hz), 135.3, 132.1, 128.9, J=7.0Hz, 3H). 13C NMR (125.76MHz, CDCl3): δ 171.61,

Wu et al.
7
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138.00, 128.98, 124.18, 119.84, 37.80, 31.44, 25.37, 22.45,
13.96. GC-MS (EI, 70eV): m/z=191 (M+).
N,N-Dimethylcinnamamide (3k):55 White solid; yield:
1
77% (134.8mg). Eluent: petroleum ether/EtOAc=5/1. H
NMR (500MHz CDCl3): δ 7.69 (d, J=15.5Hz, 1H), 7.56–
7.54 (m, 2H), 7.41–7.34 (m, 3H), 6.91 (d, J=15.5Hz, 1H),
3.18–3.09 (m, 6H). 13C NMR (125.76MHz, CDCl3): δ
166.7, 142.4, 135.3, 129.6, 128.8, 127.8, 117.4, 37.5, 36.0.
GC-MS (EI, 70eV): m/z=175 (M+).
(E)-1-Morpholino-3-phenylprop-2-en-1-one (3l):56 White
solid; yield: 75% (162.8mg). Eluent: petroleum ether/
EtOAc=5/1. 1H NMR (500MHz CDCl3): δ7.63 (d, J=15.5Hz,
1H), 7.47–7.45 (m, 2H), 7.33–7.28 (m, 3H), 6.78 (d, J=15.5Hz,
1H), 3.66–3.62 (m, 8H). 13C NMR (125.76MHz, CDCl3): δ
165.6, 143.3, 135.1, 129.8, 128.9, 127.8, 116.5, 66.9, 46.2,
42.5. GC-MS (EI, 70eV): m/z=217 (M+).
4-Methoxy-N-(phenylsulfonyl)benzamide (3m):57 White
solid; yield: 81% (235.7mg). Eluent: petroleum ether/
EtOAc=5/1. 1H NMR (500MHz CDCl3): δ 9.47 (brs, 1H),
8.10–8.08 (m, 2H), 7.75–7.32 (m, 2H), 7.59–7.56 (m, 1H),
7.50–7.46 (m, 2H), 6.81–6.80 (m, 2H), 3.74 (s, 3H). 13C
NMR (125.76MHz, CDCl3): δ 164.0, 163.8, 138.6, 134.0,
130.2, 129.0, 128.6, 123.1, 114.2, 55.6. GC-MS (EI, 70eV):
m/z=291 (M+).
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
Funding
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The author(s) disclosed receipt of the following financial support
for the research, authorship, and/or publication of this article: J.X.
was financially supported by the National Natural Science
Foundation of China (No. 21703061) and the Natural Science
Foundation of Hunan Province (No. 2017JJ3081).
ORCID iD
Jing Xiao
https://orcid.org/0000-0002-7523-2303
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Supplemental material
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