Base-catalyzed retro-Claisen condensation: A convenient esterification of alcohols via C-C bond cleavage of ketones to afford acylating sources

Article abstract of DOI:10.1039/c4ra04618h

The base-catalyzed esterification of alcohols via retro-Claisen condensation has been demonstrated for the first time. A variety of alcohols including aryl- and heteroaryl methanols as well as aliphatic ones underwent efficient acylation to give the ester products in reasonable to good yields upon isolation. Not only conventional 1,3-diketones but also strong electron-withdrawing group containing acetophenones could serve as the acylating suppliers. The synthetic protocol is operationally simple and adaptable to a broad substrate scope. It complements the existed esterification via the retro-Claisen condensation, and enlarges this benign synthetic methodology.

Full text of DOI:10.1039/c4ra04618h

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Base-catalyzed retro-Claisen condensation: a
convenient esterification of alcohols via C–C bond
cleavage of ketones to afford acylating sources†
Cite this: RSC Adv., 2014, 4, 29502
a
a
a
ab
*
Feng Xie, Fengxia Yan, Mengmeng Chen and Min Zhang
The base-catalyzed esterification of alcohols via retro-Claisen condensation has been demonstrated for the
first time. A variety of alcohols including aryl- and heteroaryl methanols as well as aliphatic ones underwent
efficient acylation to give the ester products in reasonable to good yields upon isolation. Not only
conventional 1,3-diketones but also strong electron-withdrawing group containing acetophenones
could serve as the acylating suppliers. The synthetic protocol is operationally simple and adaptable to a
broad substrate scope. It complements the existed esterification via the retro-Claisen condensation, and
enlarges this benign synthetic methodology.
Received 16th May 2014
Accepted 19th June 2014
DOI: 10.1039/c4ra04618h
www.rsc.org/advances
proceeds via a synergistic process of carbon–carbon (C–C) bond
cleavage of ketones and alcohol acylation. Lewis acids such as
Introduction
In(OTf)3, FeCl3 and Fe(OTf)3 have been proven to be efficient
catalysts.13 However, to the best of our knowledge, the usage of
inexpensive base catalysts for such a transformation has not
been explored yet. During the course of our study on a-alkyl-
ation of ketones,14 the reaction of pyridin-3-ylmethanol 1a with
acetylacetone 2a gave, instead of the anticipated a-alkylated
product 3a0, but the ester 3a exclusively (eqn (1)). With this new
observation, our further investigations showed that the base (t-
BuONa) served as a catalyst in the formation of desired product
3a, while the ruthenium species was not involved in the reac-
tion. Herein, we report a base-catalysed retro-Claisen conden-
sation for the rst time, providing a convenient esterication of
alcohols via C–C bond cleavage of ketones to afford acylating
sources.
Esters are known as a fundamental class of organic compounds.
The ester groups frequently occur in numerous bioactive
compounds,1 top-sold marketing medicines2a (e.g., Plavix,2b
Concerta,2c Xalatan2d), and synthetic polymers (e.g. proteins and
nylons).3 Moreover, esters could serve as interesting building
blocks for the preparation of various functionalized products.4
Due to its multiple functions, the development of efficient
esterication approaches has long been a subject of synthetic
chemists. The conventional syntheses include the Tishchenko5,6
and Fischer esterication,7 trans-esterication,8 and the
condensation or coupling reactions of alcohols with carboxylic
acids,9 anhydrides,10 acid halides.11 Interestingly, the dehydro-
genative esterication established in recent years directly from
alcohols demonstrated an alternative approach towards the
related end.12 Although these methods are currently the most
widely used, many of them suffer a number of drawbacks, such
as use of less environmentally benign halogenated reagents,
concentrated acid catalysts (i.e., HCl and H2SO4), or expensive
ligands and transition-metal catalysts, which could lead to
either easy equipment corrosion, or generation of toxic wastes.
Therefore, there is a need for the development of acid and
transition-metal catalysts free esterication approaches.
(1)
Results and discussion
In recent years, the retro-Claisen condensation has offered a
new avenue to access different type of esters. The reaction
Firstly, we tried to screen an efficient reaction system. The
synthesis of pyridin-3-ylmethyl acetate 3a from 3-pyridin-3-yl-
methanol 1a and acetylacetone 2a was chosen as a model
reaction to determine different reaction parameters. Initially,
the reaction was performed at 120 ꢀC for 12 h in the presence of
20 mol% of t-BuONa. The desired product was detected in 57%
yield upon GC analysis (Table 1, entry 1). However, the reaction
in absence of base gave only trace of expected product (Table 1,
entry 2), indicating the base is an essential catalyst in the
aSchool of Chemical & Material Engineering, Jiangnan University, Wuxi 214122,
People's Republic of China. E-mail: minzhang@scut.edu.cn; Fax: +86-020-39925999;
Tel: +86-13802538592
bSchool of Chemistry & Chemical Engineering, South China University of Technology,
381 Wushan Rd, Guangzhou 510640, People's Republic of China
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c4ra04618h
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Table 1 Screening of optimized reaction conditionsa
Table 2 Base-mediated acylation or alcohols with of 1,3-diketonesa
Entry
1
Alcohol 1
Ketone 2
3,b yield%
Entry
Base
Solvent
3a,b yield%
1
2
3
4
5
6
7
8
t-BuONa
—
K2CO3
CS2CO3
KOH
CH3ONa
NEt3
DABCO
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-Amyl alcohol
t-Amyl alcohol
t-Amyl alcohol
t-Amyl alcohol
t-Amyl alcohol
t-Amyl alcohol
t-Amyl alcohol
t-Amyl alcohol
DMSO
57
Trace
23
34
38
46
<10
31
43
41
52
68
68
68
48
82
2a: R1 ¼ Me
2
3
4
2a
2a
2a
9
10
11
12c
13d
14e
15f
16g
DMF
Toluene
t-Amyl alcohol
t-Amyl alcohol
t-Amyl alcohol
t-Amyl alcohol
t-Amyl alcohol
a
Reaction conditions: unless otherwise specied, all reactions were
carried out without inert gas protection by using 1a (1.2 mmol), 2a (1
mmol), solvent (1 mL), temperature: 120 ꢀC, base (0.2 mmol), reaction
b
c
d
time (12 h). GC yield. Base (0.3 mmol). Base (0.5 mmol).
e
g
f
Reaction temperature: 130 ꢀC. Reaction temperature: 100 ꢀC.
Reaction time: 18 h.
5
2a
6
7
8
1a
1b
1c
2b: R1 ¼ Ph
formation of product. Subsequently, under the same reaction
conditions, replacing t-BuONa with a series of other inorganic
and organic bases gave lower product yields (Table 1, entries 3–
8). Hence, we chose t-BuONa as the preferred catalyst, other
polar and less-polar solvents were showed to be less effective in
the formation of 3a comparing to t-amyl alcohol (Table 1,
entries 9–11). Gratifyingly, the increase of base loading from 20
mol% to 30 mol% led to an improved product yield (Table 1,
entry 12). However, a further increase could not improve the
product yield any more (Table 1, entry 13). Similarly, increase or
decrease of reaction temperature also failed to result in better
reaction efficiency (Table 1, entries 14–15). Finally, prolonging
the reaction time from 12 h to 18 h gave a highest yield (Table 1,
entry 16). Hence, the optimal reaction conditions can be as
indicated in entry 16 of Table 1.
With the availability of the optimized reaction conditions in
hand, we then examined the scope of the synthetic protocol.
Considering the pyridyl group containing esters could oen
exhibit some interesting biological activities,15 but the esteri-
cation of pyridyl methanols by employing retro-Claisen
condensation has been scarcely explored. Hence, we rstly
focused on the synthesis of pyridylmethyl esters. The reactions
of a variety of pyridyl methanols were examined in combination
with two representative alkyl and aryl 1,3-diketones (2a, 2b).
As shown in Table 2, all the reactions proceeded smoothly
and furnished desired esters in moderate to good yields upon
isolation (Table 2, entries 1–10). It was found that the
2b
2b
9
1d
1e
2b
10
2b
2a
11c
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Table 2 (Contd.)
Table 3 Base-catalyzed esterification alcohols with acetophenonesa
Entry
12c
Alcohol 1
Ketone 2
3,b yield%
Entry
1
Alcohol 1
Ketone 3
4,b yield%
1f
2b
1g
3a
13
2b
2b
2
3
1i
1j
3a
3a
14
a
Reaction conditions: unless otherwise specied, all reactions were
carried out in presence of 1 (1.2 mmol), 2 (1 mmol), solvent (1 mL),
b
temperature (120 ꢀC), base (0.3 mmol), reaction time (18 h). Isolated
yields. c Temperature: 130 ꢀC, time: 24 h.
4
1h
1k
3a
3a
substitution patterns of pyridyl methanols slightly affected the
product yields. Specically, the para-pyridyl methanol afforded
the corresponding products in higher yields than the meta- and
ortho-ones (Table 2, entries 1–3 and 6–8). Meanwhile, the reac-
tions using (2-chloropyridin-3-yl)methanol gave the products in
relatively lower yields, which might be attributable to the
inuence of steric hindrance (Table 2, entries 5, 10). In addi-
tion, benzylic alcohols 1f and 1g as well as aliphatic alcohol 1h
could also been acylated to afford the desired products in
good yields (Table 2, entries 11–14). Noteworthy, the reactions
of (2-nitrophenyl)methanol 1f need longer reaction time and
elevated reaction temperature to afford desirable yields. It is
conceivable that the ortho-NO2 group could signicantly
decrease the nucleophilicity of alcohol, thus disfavouring the
acylation process (Table 2, entries 11–12).
5c
6
7
1a
1b
3a
3a
Next, we turned our attention to employ less-reactive aceto-
phenones for the synthetic protocol. Firstly 1-(4-nitrophenyl)-
ethanone 3a in combination with a variety of alcohols was
tested. As shown in Table 3, all the reactions underwent effi-
ciently to afford desired products in reasonable to good isolated
yields (Table 3, entries 1–8). Simple benzylic alcohol 1g and
aliphatic ones 1j and 1h were proven to be effective coupling
partners, giving desired products in good yields (Table 3, entries
1, 3 and 4). Moreover, chloride-containing alcohols (1i, 1k)
as well as pyridyl methanols (1a, 1b and 1d) could also be
transformed into the corresponding esters in reasonable
yields (Table 3, entries 2 and 5–8). However, the reactions
of acetophenone 3b, 1-(4-methoxyphenyl)ethanone 3c and 1-(4-
uorophenyl)ethanone 3d failed to yield even trace of
expected products (Table 3, entries 9–11), attributing to the
8
1d
3a
9
10
11
1g
1g
1g
3b
3c
3d
—
—
—
a
Reaction conditions: unless otherwise specied, all reactions were
carried out without inert gas protection by using 1 (1.2 mmol), 3 (1
mmol), solvent (1 mL), temperature (120 ꢀC), base (0.3 mmol),
b
c
reaction time (18 h). Yields of isolated pure product. Temperature:
130 ꢀC, reaction time: 24 h.
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Experimental
General information
All the obtained products were characterized by melting points
(m.p), 1H-NMR, 13C-NMR infrared spectra (IR), the NMR spectra
of the known compounds were found to be identical with the
ones reported in the literatures. Additionally, the solid and new
products were further determined by melting points and mass
Scheme
alcohols.
1 The esterification of dissymmetric 1,3-diketone and
1
spectra (MS), respectively. H-NMR and 13C-NMR spectra were
obtained on a Bruker Avance 400 MHz NMR spectrometer; mass
spectra were recorded on Trace DSQ GC/MS. Melting points
were measured on an Electrothemal SGW-X4 microscopy digital
melting point apparatus and are uncorrected; IR spectra were
recorded on a Brucker Vector 22 spectrometer; chemical shis
were reported in parts per million (ppm, d) downeld from
tetramethylsilane. Proton coupling patterns are described as
singlet (s), doublet (d), triplet (t), multiplet (m); TLC was per-
formed using commercially prepared 100–400 mesh silica gel
plates (GF254), and visualization was effected at 254 nm; all the
reagents were purchased from commercial sources (J&K
Chemic, TCI, Fluka, Acros, SCRC), and used without further
purication.
Scheme 2 Proposed mechanism for the esterification of keones.
acetophenones lacking an strong electron-withdrawing group
disfavor of the C–C bond cleavage between the carbonyl group
and the a-position.
Typical procedure for the synthesis of 3-pyridylmethyl acetate
3a
Finally, unsymmetrical 1-phenylbutane-1,3-dione 2c was
used in combination with pyridin-2-ylmethanol 1c to investigate
the reaction chemoselectivity, which could lead to two possible
isomers 3c and 3h. Interestingly, except for the generation
acetophenone 3b, ester 3c and 3h were observed in a ratio of
10 : 1 (Scheme 1). The selectivity is associated with the sterically
less hindered acyl moiety favor the acylation of alcohol.
Based on the retro-Claisen condensation,16 a plausible
pathway for the generation of esters from alcohols and ketones
is depicted in Scheme 2. The reaction initiated with t-BuONa-
induced deprotonation of alcohol 1 to form alkoxy anion A, A
undergoes a nucleophilic attack to the carbonyl group of ketone
and affords intermediate B. Then, by abstracting a proton from
the in situ formed t-BuOH, the thermodynamic favorable C–C
bond cleavage of B in a retro-Aldol manner would afford the
desired product, regenerate the t-BuONa catalyst and release the
side product R3Me, respectively.
t-BuONa (0.028 g, 0.3 mmol), 3-(hydroxymethyl)pyridine 1a
(0.131 g, 1.2 mmol), acetylacetone 2a (0.1 g, 1 mmol) and t-amyl
alcohol (1 mL) were added successively to a Schlenk tube, it was
ꢀ
then closed and the resulting mixture was heated at 120 C for
18 h in an oil bath. Aer cooling down to room temperature, the
reaction mixture was then ltered and concentrated under
vacuum, the obtained crude product was directly puried by
preparative TLC on silica, eluting with petroleum ether (60–
90 ꢀC)–ethyl acetate (3 : 1) to give 3-pyridylmethyl acetate 3a as a
yellow oil (0.110 g, 75%).
Analytic data of the obtained compounds
1
3-Pyridylmethyl acetate (3a). Yellow oil; H NMR (400 MHz,
CDCl3): d 8.62 (d, J ¼ 1.6 Hz, 1H), 8.58 (dd, J ¼ 4.8, 1.6 Hz, 1H),
7.70 (dt, J ¼ 7.6, 2.0 Hz, 1H), 7.33–7.29 (m, 1H), 5.13 (s, 2H), 2.11
(s, 3H); 13C NMR (101 MHz, CDCl3): d 170.71, 149.67, 149.61,
136.07, 131.63, 123.47, 63.72, 20.87; IR (neat): 2926, 1746, 1579,
1481, 1381, 1364, 1235, 1027, 873, 795, 713 cmꢁ1; MS (EI, m/z):
Conclusions
In summary, we have demonstrated a base-catalyzed esteri- 151.11 [M]+.
1
cation of alcohols via retro-Claisen condensation for the rst 4-Pyridylmethyl acetate (3b). Yellow oil; H NMR (400 MHz,
time. A variety of alcohols including aryl- and heteroaryl CDCl3): d 8.54 (d, J ¼ 5.6 Hz, 2H), 7.20 (d, J ¼ 5.2 Hz, 2H), 5.07 (s,
methanols as well as aliphatic ones underwent efficient acyl- 2H), 2.11 (s, 3H); 13C NMR (101 MHz, CDCl3): d 170.50, 149.99,
ation to give the ester products in reasonable to good isolated 144.97, 121.94, 64.26, 20.79; IR (neat): 2930, 1746, 1606, 1563,
yields. Not only conventional 1,3-diketones but also strong 1417, 1383, 1365, 1234, 1045, 800 cmꢁ1; MS (EI, m/z): 151.08
electron-withdrawing group containing acetophenones could [M]+.
1
serve as the acylating suppliers. The synthetic protocol is
2-Pyridylmethyl acetate (3c). Yellow oil; H NMR (400 MHz,
operationally simple and adaptable to a broad substrate CDCl3): d 8.53 (d, J ¼ 4.8 Hz, 1H), 7.63 (td, J ¼ 8.0, 2.0 Hz, 1H),
scope. It complements the existed esterication via the retro- 7.28 (d, J ¼ 7.6 Hz, 1H), 7.16 (dd, J ¼ 7.2, 5.2 Hz, 1H), 5.15 (s,
Claisen condensation, and enlarges this benign synthetic 2H), 2.09 (s, 3H); 13C NMR (101 MHz, CDCl3): d 170.68, 155.77,
methodology.
149.52, 136.76, 122.88, 121.87, 66.87, 20.91; IR (neat): 2924,
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2853, 1738, 1637, 1459, 1130, 638 cmꢁ1; MS (EI, m/z): 151.11 129.00, 128.77, 124.99, 62.89, 20.73; IR (neat): 2959, 2925, 1723,
[M]+.
(4-Chloropyridin-2-yl)methyl acetate (3d). Yellow oil; 1H
1575, 1437, 1312, 1108, 991, 732 cmꢁ1; MS (EI, m/z): 195.03 [M]+.
2-Nitrobenzyl benzoate (3l). Gray solid; m.p: 113–115 ꢀC
NMR (400 MHz, CDCl3): d 8.49 (d, J ¼ 5.2 Hz, 1H), 7.37 (d, J ¼ 1.6 (lit,16a 101–102 ꢀC); 1H NMR (400 MHz, CDCl3): d 8.06–7.96 (m,
Hz, 1H), 7.25 (dd, J ¼ 5.2, 1.6 Hz, 1H), 5.21 (s, 2H), 2.18 (s, 3H); 3H), 7.63–7.47 (m, 3H), 7.44–7.34 (m, 3H), 5.68 (s, 2H); 13C NMR
13C NMR (101 MHz, CDCl3): d 170.47, 157.59, 150.35, 144.91, (101 MHz, CDCl3): d 165.94, 147.62, 133.84, 133.42, 132.36,
123.21, 122.00, 66.13, 20.85; IR (neat): 2959, 2925, 1738, 1637, 129.78, 129.59, 128.93, 128.82, 128.58, 125.11, 63.35; IR (neat):
1450, 1106, 619 cmꢁ1; MS (EI, m/z): 185.97 [M + 1]+.
2923, 2849, 1718, 1598, 1575, 1521, 1436, 1372, 1336, 1312,
(2-Chloropyridin-3-yl)methyl acetate (3e). Yellow oil; 1H 1272, 1119, 1069, 1028, 991, 860, 796, 715, 661 cmꢁ1; MS (EI, m/
NMR (400 MHz, CDCl3): d 8.36 (dd, J ¼ 4.8, 1.6 Hz, 1H), 7.82– z): 257.05 [M]+.
7.72 (m, 1H), 7.33–7.24 (m, 1H), 5.21 (s, 2H), 2.16 (s, 3H); 13C
Benzyl benzoate (3m). Light yellow oil; H NMR (400 MHz,
1
NMR (101 MHz, CDCl3): d 170.40, 150.27, 149.05, 138.00, CDCl3): d 7.99 (d, J ¼ 8.0 Hz, 2H), 7.46 (t, J ¼ 7.6 Hz, 1H), 7.40–
130.51, 122.56, 62.61, 20.73; IR (neat): 2958, 2852, 1742, 1637, 7.21 (m, 7H), 5.28 (s, 2H); 13C NMR (101 MHz, CDCl3): d 166.46,
1414, 1107, 992, 619 cmꢁ1; MS (EI, m/z): 185.98 [M + 1]+.
136.11, 133.06, 130.19, 129.74, 128.63, 128.41, 128.27, 128.20,
3-Pyridylmethyl benzoate (3f). Yellow oil; 1H NMR (400 MHz, 66.72; IR (neat): 3066, 3034, 1718, 1637, 1451, 1270, 1107, 710,
CDCl3): d 8.62 (s, 1H), 8.53–8.44 (m, 1H), 8.02–7.89 (m, 2H), 7.67 618 cmꢁ1; MS (EI, m/z): 211.94 [M]+.
(dd, J ¼ 8.0, 1.6 Hz, 1H), 7.50–7.41 (m, 1H), 7.37–7.28 (m, 2H),
Pentyl benzoate (3n). Colorless oil; 1H NMR (400 MHz,
7.20 (dd, J ¼ 8.0, 5.6 Hz, 1H), 5.27 (s, 2H); 13C NMR (101 MHz, CDCl3): d 8.08 (s, 1H), 8.06 (d, J ¼ 1.2 Hz, 1H), 7.57 (t, J ¼ 7.6 Hz,
CDCl3): d 166.19, 149.61, 135.97, 133.23, 131.73, 129.72, 129.68, 1H), 7.46 (t, J ¼ 8.0 Hz, 2H), 4.34 (t, J ¼ 6.8 Hz, 2H), 1.86–1.75 (m,
128.44, 123.49, 64.11; IR (neat): 3963, 3030, 1719, 1602, 1579, 2H), 1.52–1.35 (m, 4H), 0.96 (t, J ¼ 6.8 Hz, 3H); 13C NMR (101
1484, 1453, 1427, 1374, 1315, 1272, 1181, 1110, 1070, 1025, 946, MHz, CDCl3): d 166.69, 132.77, 130.57, 129.54, 128.31, 65.12,
796, 710 cmꢁ1; MS (EI, m/z): 214.03 [M + 1]+.
28.45, 28.21, 22.37, 13.98; IR (neat): 2958, 2932, 2361, 1720,
4-Pyridylmethyl benzoate (3g). Yellow oil; 1H NMR (400 MHz, 1637, 1451, 1384, 1107, 710, 618 cmꢁ1; MS (EI, m/z): 192.09 [M]+.
1
CDCl3): d 8.51 (d, J ¼ 4.4 Hz, 2H), 8.00 (d, J ¼ 8.0 Hz, 2H), 7.54–
Benzyl-4-nitrobenzoate (4a). Yellow oil; H NMR (400 MHz,
7.42 (m, 1H), 7.37–7.33 (m, 2H), 7.23 (d, J ¼ 5.2 Hz, 2H), 5.27 (s, CDCl3): d 8.23–8.15 (m, 4H), 7.41–7.28 (m, 5H), 5.34 (s, 2H); 13
C
2H); 13C NMR (101 MHz, CDCl3): d 165.00, 148.99, 144,08, NMR (101 MHz, CDCl3): d 163.52, 149.58, 134.49, 134.22,
132.37, 128.70, 128.52, 127.51, 120.83, 63.59; IR (neat): 3037, 129.81, 127.73, 127.64, 127.42, 122.53, 66.64; IR (neat): 2925,
1722, 1602, 1561, 1450, 1378, 1278, 1175, 1109, 1072, 1026, 797, 1712, 1605, 1524, 1456, 1348, 1271, 1103, 870, 744, 715 cmꢁ1
;
714 cmꢁ1; MS (EI, m/z): 214.05 [M + 1]+.
MS (EI, m/z): 257.04 [M]+.
2-Pyridylmethyl benzoate (3h). Brown oil; 1H NMR (400 MHz,
4-Chlorobenzyl-4-nitrobenzoate (4b). Yellow solid, m.p: 110–
1
ꢀ
CDCl3): d 8.61 (d, J ¼ 4.0 Hz, 1H), 8.13 (s, 1H), 8.11 (d, J ¼ 1.2 Hz, 111 C; H NMR (400 MHz, CDCl3): d 8.22 (d, J ¼ 8.8 Hz, 2H),
1H), 7.71 (td, J ¼ 8.0, 2.0 Hz, 1H), 7.46 (d, J ¼ 7.6 Hz, 2H), 7.44 (d, 8.15 (d, J ¼ 8.8 Hz, 2H), 7.36–7.28 (m, 4H), 5.30 (s, 2H); 13C NMR
J ¼ 1.2 Hz, 1H), 7.24 (dd, J ¼ 7.2, 5.2 Hz, 1H); 13C NMR (101 (101 MHz, CDCl3): d 164.45, 150.69, 135.30, 134.67, 133.73,
MHz, CDCl3): d 166.21, 156.05, 149.48, 136.78, 133.18, 129.90, 130.83, 129.87, 128.98, 123.60, 66.83; IR (neat): 3054, 1732,
129.80, 128.43, 122.85, 121.67, 67.22; IR (neat): 3055, 1721, 1637, 1399, 1107, 992, 618 cmꢁ1; MS (EI, m/z): 290.97 [M]+.
1636, 1475, 1384, 1275, 1109, 992, 756, 618 cmꢁ1; MS (EI, m/z):
Butyl-4-nitrobenzoate (4c). Yellow oil; 1H NMR (400 MHz,
CDCl3): d 8.30–8.15 (m, 2H), 8.16–8.04 (m, 2H), 4.30 (m, 2H),
214.05 [M + 1]+.
(4-Chloropyridin-2-yl)methyl benzoate (3i). Brown oil; 1H 1.74–1.66 (m, 2H), 1.46–1.35 (m, 2H), 0.94–0.85 (m, 3H); 13C
NMR (400 MHz, CDCl3): d 8.52 (d, J ¼ 5.2 Hz, 1H), 8.14 (dd, J ¼ NMR (101 MHz, CDCl3): d 163.75, 149.49, 134.88, 129.64,
8.0, 1.6 Hz, 2H), 7.62 (t, J ¼ 7.2 Hz, 1H), 7.49 (t, J ¼ 8.0 Hz 3H), 122.50, 64.81, 29.63, 18.21, 12.70; IR (neat): 2961, 2932, 2874,
7.27 (dd, J ¼ 5.6, 2.0 Hz, 1H), 5.49 (s, 2H); 13C NMR (101 MHz, 1727, 1608, 1520, 1351, 1278, 1103, 1016, 874, 784, 720 cmꢁ1
CDCl3): d 166.05, 157.84, 150.35, 144.95, 133.36, 129.83, 129.60, MS (EI, m/z): 223.06 [M]+.
;
128.52, 123.23, 121.89, 66.51. IR (neat): 3062, 3011, 1724, 1637,
Pentyl-4-nitrobenzoate (4d). Colorless oil; 1H NMR (400
1578, 1451, 1314, 1110, 709, 619 cmꢁ1; MS (EI, m/z): 248.01 MHz, CDCl3): d 8.32–8.26 (m, 2H), 8.21 (dt, J ¼ 8.8, 2.0 Hz, 2H),
[M + 1]+.
4.37 (t, J ¼ 6.4 Hz, 2H), 1.85–1.75 (m, 2H), 1.46–1.37 (m, 4H),
(2-Chloropyridin-3-yl)methyl benzoate (3j). Brown solid. 0.94 (t, J ¼ 7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3): d 164.76,
m.p: 81–83 ꢀC; 1H NMR (400 MHz, CDCl3): d 8.38 (dd, J ¼ 4.8, 1.6 150.51, 135.91, 130.66, 123.52, 66.11, 28.31, 28.13, 22.32, 13.95;
Hz, 1H), 8.09 (dd, J ¼ 8.0, 1.2 Hz, 2H), 7.85 (dd, J ¼ 7.6, 1.2 Hz, IR (neat): 2959, 2926, 1725, 1630, 1530, 1384, 1105, 991, 619
1H), 7.59 (t, J ¼ 7.2 Hz, 1H), 7.47 (t, J ¼ 7.6 Hz, 2H), 7.32–7.25 (m, cmꢁ1; MS (EI, m/z): 237.08 [M]+.
1H), 5.46 (s, 2H); 13C NMR (101 MHz, CDCl3): d 166.03, 150.40,
4-Chlorophenethyl 4-nitrobenzoate (4e). Yellow solid, m.p:
1
ꢀ
149.14, 138.04, 133.42, 130.68, 129.76, 129.53, 128.55, 122.62, 103–104 C; H NMR (400 MHz, CDCl3): d 8.21 (d, J ¼ 8.4 Hz,
63.05; IR (neat): 3058, 1740, 1637, 1385, 1107, 992, 619 cmꢁ1; MS 2H), 8.08 (d, J ¼ 8.8 Hz, 2H), 7.23 (d, J ¼ 8.0 Hz, 2H), 7.13 (d, J ¼
(EI, m/z): 248.01 [M + 1]+.
8.4 Hz, 2H), 4.50 (t, J ¼ 6.8 Hz, 2H), 3.00 (t, J ¼ 6.8 Hz, 2H); 13
C
2-Nitrobenzyl acetate (3k). Yellow oil; 1H NMR (400 MHz, NMR (101 MHz, CDCl3): d 164.54, 150.62, 135.90, 135.47,
CDCl3): d 8.00 (d, J ¼ 8.0 Hz, 1H), 7.57 (t, J ¼ 7.6 Hz, 1H), 7.51 (d, 132.72, 130.67, 130.21, 128.81, 123.60, 65.96, 34.47; IR (neat):
J ¼ 7.6 Hz, 1H), 7.40 (t, J ¼ 7.6 Hz, 1H), 5.41 (s, 2H), 2.07 (s, 3H); 2923, 1718, 1637, 1525, 1384, 1107, 992, 618 cmꢁ1; MS (EI, m/z):
13C NMR (101 MHz, CDCl3): d 170.33, 147.52, 133.77, 132.11, 305.03 [M]+.
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3-Pyridylmethyl-4-nitrobenzoate (4f). Yellow solid, m.p: 133–
RSC Advances
M. Centofanti, E. Campos and L. Rossetti, J. Glaucoma.,
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135 ꢀC (lit,16b 140–142 ꢀC); 1H NMR (400 MHz, CDCl3): d 8.67 (s,
1H), 8.57 (d, J ¼ 4.8 Hz, 1H), 8.23 (d, J ¼ 8.8 Hz, 2H), 8.16 (d, J ¼
8.8 Hz, 2H), 7.73 (d, J ¼ 7.6 Hz, 1H), 7.29 (dd, J ¼ 8.0, 5.2 Hz,
1H), 5.36 (s, 2H); 13C NMR (101 MHz, CDCl3): d 164.40, 150.73,
150.03, 149.86, 136.31, 135.06, 130.97, 130.86, 123.65, 123.64,
65.08; IR (neat): 2925, 1722, 1601, 1522, 1347, 1284, 1124, 853,
796, 716 cmꢁ1; MS (EI, m/z): 258.04 [M]+.
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4-Pyridylmethyl-4-nitrobenzoate (4g). Yellow solid, m.p: 143–
1
ꢀ
145 C; H NMR (400 MHz, CDCl3): d 8.59 (dd, J ¼ 4.4, 1.6 Hz,
2H), 8.26 (dd, J ¼ 7.2, 2.0 Hz, 2H), 8.20 (dd, J ¼ 7.2, 2.0 Hz, 2H),
7.27 (d, J ¼ 6.0 Hz, 2H), 5.36 (s, 2H); 13C NMR (101 MHz, CDCl3):
d 164.25, 150.92, 150.16, 144.27, 134.85, 130.90, 123.71, 122.07,
65.54; IR (neat): 2925, 1722, 1601, 1522, 1347, 1284, 1124, 853,
796, 716 cmꢁ1; MS (EI, m/z): 258.04 [M]+.
(2-Chloropyridin-3-yl)methyl 4-nitrobenzoate (4h). Brown
solid; m.p: 122–124 ꢀC; 1H NMR (400 MHz, CDCl3): d 8.42 (dd, J
¼ 4.8, 2.0 Hz, 1H), 8.31 (dt, J ¼ 9.2, 2.0 Hz, 2H), 8.26 (dt, J ¼ 9.2,
2.0 Hz, 2H), 7.85 (dd, J ¼ 7.6, 2.0 Hz, 1H), 7.32 (dd, J ¼ 7.6, 4.8
Hz, 1H), 5.51 (s, 2H); 13C NMR (101 MHz, CDCl3): d 164.26,
150.88, 150.82, 149.67, 138.65, 134.88, 130.92, 129.83, 123.70,
122.68, 64.12; IR (neat): 2957, 1748, 1637, 1458, 1384, 1061, 991,
619 cmꢁ1; MS (EI, m/z): 291.99 [M]+.
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Acknowledgements
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The authors are grateful to the funds of the “National Natural
Science Foundation of China (21101080)”, “Natural Science
Foundation of Jiangsu Province (BK2011144)”, “Funda-
mental Research Funds for the Central Universities of
China (2014ZZ0047)”, and “Distinguished talent program of
SCUT”.
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