A novel metal-free reductive esterification of N-tosylhydrazones with carboxylic acids

Article abstract of DOI:10.1002/cjoc.201200387

A novel method for the synthesis of esters via reductive coupling of N-tosylhydrazones with carboxylic acids under metal-free conditions has been developed. Various functional groups were found to be tolerable under the reaction conditions to afford low to good yields.

Full text of DOI:10.1002/cjoc.201200387

FULL PAPER
DOI: 10.1002/cjoc.201200387
A Novel Metal-free Reductive Esterification of
N-Tosylhydrazones with Carboxylic Acids
Zhou, Ankun(周安坤)
Wu, Lei(吴磊)
Li, Dazhi(李大志)
Chen, Qingqing(陈庆庆)
Zhang, Xiao(张晓)
Xia, Wujiong*(夏吾炯)
State Key Lab of Urban Water Resource and Environment, the Academy of Fundamental and Interdisciplinary
Sciences, Harbin Institute of Technology, Harbin, Heilongjiang 150080, China
A novel method for the synthesis of esters via reductive coupling of N-tosylhydrazones with carboxylic acids
under metal-free conditions has been developed. Various functional groups were found to be tolerable under the re-
action conditions to afford low to good yields.
Keywords metal-free, N-tosylhydrazones, esterification, carboxylic acids
Introduction
To further explore the generality of this novel reduc-
tive esterification reaction, we screened the substrate
scopes from aromatic to aliphatic carboxylic acids under
the optimized conditions. As shown in Table 1, all of
the screened carboxylic acids were proven to be reliable
substrates affording the corresponding esters with low
to good yields. Aromatic carboxylic acids bearing
electron-donating groups (2,6-dimethyl, m-phenoxy,
o-methoxy) exhibited better yields than those with
electron-withdrawing groups (o-I, p-NO2, p-formyl), for
an instance, para-substituted nitro group impaired the
yield to 30% (Entry 6). Using DMF as solvent
occasionally enhanced the reaction yields (Entries 5—8).
It is worth mentioning that the formyl-group does
survive in this reductive esterification conditions, albeit
with only low yield as 36% in DMF (Entry 7). Aliphatic
carboxylic acids afforded medium yields to correspond-
ing esters, and even for high steric trimethylacetic acid,
the reaction took place smoothly to give 60% yield
(Entry 9).
Further extension of scopes for N-tosylhydrazones
was also investigated. As depicted in Table 2, the
N-tosylhydrazones applied can be conjugated with aro-
matic rings bearing electron-rich and electron-deficient
substituents giving medium to good yields (Entries
1—8). Apparently, electron-deficient substituents (En-
tries 2, 4, 6) enervated the carbene intermediates which
led to lower yields as compared with substrates with
electron-rich groups. Delightfully, tosylhydrazones with
aliphatic skeletons were also proven to be good sub-
strates for this novel reductive esterification reaction
(Entries 9, 10). Furthermore, the tosylhydrazones pre-
pared from aromatic or aliphatic aldehydes were
Since the discovery of N-tosylhydrazone in the
mid-20th century, it has been a versatile synthetic
intermediate for almost 60 years.[1] Most leading
scientists shed light on metal catalyzed cross-coupling
reactions of N-tosylhydrazone with aryl halides,[2] aryl
sulfonates,[3] alkynes,[4] azoles,[5] and in the cascade
carbonylation,[6] which have shown generality of this
reagent to build useful functionalities for synthetic
compounds. However, in the course of this research, the
metal-free reactions with regard to tosylhydrazones
were limited to certain reactions, to the best of our
knowledge, only four reports on the use of tosyl-
hydrazones with pinacolborane,[7] arylboronic acids,[8]
alcohols,[9] and thiols[10] were documented (Scheme 1).
Inspired from the mechanism proposed by Valdés,[8,9]
we hypothesized that carboxylic acids could be a decent
nucleophile to attack the diazo intermediate under the
standard conditions. Thus, herein, we will describe this
metal-free reductive coupling as a novel and straight-
forward approach to synthesize esters.
Results and Discussion
To test our hypothesis, 3-phenoxybenzoic acid (1c)
and 1-(1-(4-methoxy phenyl) ethylidene)-2-tosylhy-
drazine (2c) were refluxed in 1,4-dioxane with the
presence of 4 equiv. K2CO3. With the same substrate
molar ratio, the reaction underwent sluggishly. However,
excess tosylhydrazones improved the yield dramatically.
As for optimized conditions, 2 equiv. of tosylhydra-
zones increased the isolated yield up to 86% (Scheme
2).
*
E-mail: xiawj@hit.edu.cn; Tel.: 0086-0451-86403193
Received April 23, 2012; accepted May 22, 2012; published online XXXX, 2012.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201200387 or from the author.
Chin. J. Chem. 2012, XX, 1—5
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Zhou et al.
FULL PAPER
Scheme 1 Metal-free reductive coupling reactions of N-tosylhydrazones
Ar
or
R1
R2
NNHTs
R2
K2CO3
ArB(OH)2
or
1)
Ref. [7,8]
R1
+
B(OR)2
HB(OR)2
R1
R2
OR3
R2
NNHTs
R2
K2CO3
K2CO3
R3OH
R3SH
2)
3)
R1
+
+
Ref. [9]
R1
SR3
R2
NNHTs
R2
R1
Ref. [10]
R1
O
NNHTs
R2
K2CO3
O
R3
R3COOH
4)
This work
R1
+
R1
R2
Scheme 2 The optimization of reaction conditions
O
NNHTs
4 equiv. K2CO3
Dioxane, 110 oC
O
O
O
+
COOH
MeO
MeO
1c
2c
3c
1c : 2c = 1 : 1.2, 48%
1c : 2c = 1 : 2, 86%
Table 1 The scope of carboxylic acidsa
tolerant with the reaction conditions to form the
corresponding esters in moderate to high yields (Entries
11—14).
NNHTs
R
4 equiv. K2CO3
O
O
+
R
COOH
Dioxane, 110 oC
MeO
Experimental
MeO
For a typical reaction, 0.5 mmol carboxylic acid, 1
mmol N-tosylhydrazone and 2 mmol K2CO3 were
charged into 25 mL oven-dried flask, and backfilled
3a - 3m
Entry
1
R
Product
Yieldb,c/%
40 (71)
Ph
3a
with nitrogen three times.
5 mL fresh-distilled
1,4-dioxane or DMF was then injected into the flask,
followed by heating up to 110 ℃ for 18 h. The
reaction was monitored by TLC until starting materials
consumed, then removed all of the volatiles for further
purification on silica chromatography.
2
2,6-Dimethyl-C6H3
m-PhO-C6H4
o-MeO-C6H4
o-I-C6H4
3b
3c
3d
3e
3f
66
3
86
4
59
5
40 (48)
30 (49)
Trace (36)
25 (53)
60
1-(4-Methoxyphenyl) ethyl benzoate (3a) 1H
NMR (400 MHz, CDCl3) δ: 8.09 (d, J＝6.8 Hz, 2H),
7.57 (t, J＝7.2 Hz, 1H), 7.46 (t, J＝7.6 Hz, 2H), 7.42 (d,
J＝8.4 Hz, 2H), 6.93 (d, J＝8.8 Hz, 2H), 6.13 (q, J＝
6.4 Hz, 1H), 3.83 (s, 3H), 1.69 (d, J＝6.4 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ: 165.9, 159.3, 133.9, 132.8,
130.7, 129.6, 128.3, 127.6, 113.9, 72.6, 55.3, 22.2;
6
p-NO2-C6H4
p-Formyl-C6H4
trans-PhCH＝CH2
—t-Bu
7
3g
3h
3i
8
9
10
—i-Bu
3j
51
11
Diphenyacetic acid
3k
70
＋
a
HRMS (ESI) calcd for C16H16O3Na [M ＋ Na]
0.5 mmol carboxylic acid, 1 mmol N-tosylhydrazone and 2
mmol K2CO3, 18 h; b Isolated yield; c DMF as solvent in paren-
theses.
279.0997, found 279.1001.
1-(4-Methoxyphenyl)ethyl 2,6-dimethylbenzoate
2
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Chin. J. Chem. 2012, XX, 1—5

A Novel Metal-free Reductive Esterification of N-Tosylhydrazones with Carboxylic Acids
Table 2 The scope of N-tosylhydrazonesa
6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 165.4,
159.3, 159.2, 134.1, 133.4, 131.6, 127.6, 120.5, 120.1,
113.8, 112.1, 72.4, 56.0, 55.3, 22.2; HRMS (ESI) calcd
for C17H18O4Na [M＋Na]＋ 309.1097, found 309.1094.
1-(4-Methoxyphenyl)ethyl 2-iodobenzoate (3e)
1H NMR (400 MHz, CDCl3) δ: 8.00 (d, J＝8.0 Hz, 1H),
7.80 (dd, J＝1.6, 7.6 Hz, 1H), 7.39—7.45 (m, 3H), 7.15
(t, J＝7.6 Hz, 1H), 6.93 (d, J＝8.4 Hz, 2H), 6.15 (q, J＝
6.4 Hz, 1H), 3.84 (s, 3H), 1.72 (d, J＝6.8 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ: 165.9, 159.4, 141.3, 135.5,
133.2, 132.5, 130.9, 127.9, 127.8, 113.9, 94.0, 73.8,
55.3, 22.0; HRMS (ESI) calcd for C16H15IO3Na [M＋
Na]＋ 404.9958, found 404.9965.
R4
R3
NNHTs
R2
4 equiv. K2CO3
COOH
+
R1
Dioxane, 110 o
C
R3
R2
R1
R3
O
R4
O
R3
4a - 4n
Entry
R3＝H, R4＝Ph—O—
Product Yieldb,c/%
1-(4-Methoxyphenyl)ethyl 4-nitrobenzoate (3f)
1H NMR (400 MHz, CDCl3) δ: 8.30 (d, J＝8.8 Hz, 2H),
8.24 (d, J＝8.8 Hz, 2H), 7.42 (d, J＝8.8 Hz, 2H), 6.94
(d, J＝8.4 Hz, 2H), 6.15 (q, J＝6.4 Hz, 1H), 3.84 (s,
3H), 1.72 (d, J＝6.4 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ: 164.0, 159.6, 150.5, 136.0, 133.0, 130.7,
R1
Ph
R2
1
2
3
4
5
6
7
8
9
10
CH3
4a
4b
56
42
o-BrC6H4
p-MeOC6H4
p-CF3C6H4
p-ClC6H4
m-NO2C6H4
Ph
CH3
CH3
4c (3c) 86
CH3
4d
4e
4f
27
127.7, 123.5, 114.0, 74.0, 55.3, 21.9; HRMS (ESI) calcd
CH3
71
＋
for C16H15NO5Na [M ＋ Na]
324.0842, found
CH3
40
324.0836.
CH2CH3
CH3
4g
4h
4i
66
1-(4-methoxyphenyl) ethyl 4-formylbenzoate (3g)
1H NMR(400 MHz, CDCl3) δ: 10.12 (s, 1H), 8.24 (d,
J＝8.0 Hz, 2H), 7.97 (d, J＝8.0 Hz, 2H), 7.43 (d, J＝
8.4 Hz, 2H), 6.94 (d, J＝8.8 Hz, 2H), 6.15 (q, J＝6.4 Hz,
1H), 3.84 (s, 3H), 1.71 (d, J＝6.4 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ: 191.7, 164.8, 159.5, 139.1, 135.6,
p-CH3C6H4
Cyclohexane
C3H7
60
38 (58)
66
CH3
4j
R3＝CH3, R4＝H
11
12
13
14
H
H
H
H
Ph
4k
4l
85
89
55
56
133.3, 130.2, 129.5, 127.7, 114.0, 73.5, 55.3, 22.0;
＋
p-OCH3-C6H4
HRMS (ESI) calcd for C17H16O4Na [M ＋ Na]
307.0946, found 307.0950.
p-F-C6H4
4m
4n
(E)-1-(4-Methoxyphenyl) ethyl cinnamate (3h)
1H NMR (400 MHz, CDCl3) δ: 7.71 (d, J＝16.0 Hz,
1H), 7.53—7.56 (m, 2H), 7.38—7.41 (m, 5H), 6.93 (d,
J＝8.4 Hz, 2H), 6.48 (d, J＝16 Hz, 1H), 6.02 (q, J＝6.4
Hz, 1H), 3.84 (s, 3H), 1.64 (d, J＝6.8 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ: 166.3, 159.3, 144.7, 134.5,
133.8, 130.2, 128.9, 128.1, 127.6, 118.5, 113.9, 72.1,
55.3, 22.0; HRMS (ESI) calcd for C18H18O3Na [M＋
Na]＋ 305.1148, found 305.1151.
CH(CH3)2
a 0.5 mmol carboxylic acid, 1 mmol N-tosylhydrazone and 2 mol
K2CO3, 18 h; b Isolated yield; c DMF as solvent in parentheses.
(3b) 1H NMR (400 MHz, CDCl3) δ: 7.41 (d, J＝8.4
Hz, 2H), 7.19 (t, J＝6.8 Hz, 1H), 7.03 (d, J＝7.6 Hz,
2H), 6.92 (d, J＝8.4 Hz, 2H), 6.16 (q, J＝6.4 Hz, 1H),
3.84 (s, 3H), 2.26 (s, 6H), 1.68 (d, J＝6.4 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ: 169.3, 159.4, 134.7, 134.2,
1-(4-Methoxyphenyl) ethyl pivalate (3i) 1H NMR
(400 MHz, CDCl3) δ: 7.20 (d, J＝8.8 Hz, 2H), 6.80 (d,
J＝8.8 Hz, 2H), 5.73 (q, J＝6.4 Hz, 1H), 3.73 (s, 3H),
1.42 (d, J＝6.8 Hz, 3H), 1.12 (s, 9H); 13C NMR (100
MHz, CDCl3) δ: 177.7, 159.1, 134.3, 127.2, 113.8, 71.6,
55.2, 38.7, 27.1, 22.2. HRMS (ESI) calcd for
C18H18O3Na [M＋Na]＋ 259.1310, found 259.1307.
1-(4-Methoxyphenyl)ethyl 3-methylbutanoate (3j)
1H NMR (400 MHz, CDCl3) δ: 7.32 (d, J＝8.4 Hz, 2H),
6.90 (d, J＝8.4 Hz, 2H), 5.89 (q, J＝6.4 Hz, 1H), 3.83
(s, 3H), 2.21 (d, J＝7.2 Hz, 2H), 2.05—2.17 (m, 1H),
1.54 (d, J＝6.8 Hz, 3H), 0.95 (d, J＝6.8 Hz, 6H); 13C
NMR (100 MHz, CDCl3) δ: 172.5, 159.2, 133.9, 127.6,
113.8, 71.7, 55.3, 43.8, 25.8, 22.4, 22.3, 22.0; HRMS
(ESI) calcd for C14H20O3Na [M ＋ Na] ＋ 259.1310,
found 259.1312.
133.3, 129.1, 128.0, 127.5, 113.8, 72.8, 55.3, 21.8, 19.5;
HRMS (ESI) calcd for C18H20O3Na [M ＋ Na]
307.1305 , found 307.1304.
＋
1-(4-Methoxyphenyl)ethyl 3-phenoxybenzoate (3c)
1H NMR (400 MHz, CDCl3) δ: 7.83 (s, 1H), 7.73 (t, J＝
7.0 Hz, 1H), 7.36—7.44 (m, 5H), 7.21 (dd, J＝2.4, 8.4
Hz, 1H), 7.17 (t, J＝7.2 Hz, 1H), 7.04 (d, J＝7.6 Hz,
2H), 6.92 (d, J＝8.8 Hz, 2H), 6.11 (q, J＝6.4 Hz, 1H),
3.83 (s, 3H), 1.67 (d, J＝6.8 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ: 165.3, 159.3, 157.4, 156.7, 133.7,
132.5, 129.9, 129.7, 127.6, 124.4, 123.7, 123.2, 119.8,
119.1, 113.9, 73.0, 55.3, 22.2; HRMS (ESI) calcd for
C22H20O4Na [M＋Na]＋ 371.1254; found 371.1254.
1-(4-Methoxyphenyl)ethyl 2-methoxybenzoate (3d)
1H NMR (400 MHz, CDCl3) δ: 7.83 (dd, J＝1.6, 8.0 Hz,
1H), 7.46—7.50 (m, 1H), 7.43 (d, J＝8.4 Hz, 2H),
6.97—7.01 (m, 2H), 6.92 (d, J＝8.8 Hz, 2H), 6.13 (q,
J＝6.4 Hz, 1H), 3.92 (s, 3H), 3.83 (s, 3H), 1.67 (d, J＝
1-(4-Methoxyphenyl) ethyl 2,2-diphenylacetate
(3k) 1H NMR (400 MHz, CDCl3) δ: 7.22—7.35 (m,
Chin. J. Chem. 2012, XX, 1—5
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Zhou et al.
FULL PAPER
12H), 6.87 (d, J＝8.8 Hz, 2H), 5.96 (q, J＝6.4 Hz, 1H),
5.07 (s, 1H), 3.83 (s, 3H), 1.55 (d, J＝6.8 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ: 171.7, 159.3, 138.8, 138.6,
133.4, 128.7, 128.6, 128.5, 127.6, 127.2, 127.1, 113.7,
72.9, 57.2, 55.3, 21.9; HRMS (ESI) calcd for
C23H22O3Na [M＋Na]＋ 369.1461, found 369.1458.
1-Phenylethyl 3-phenoxybenzoate (4a) 1H NMR
(400 MHz, CDCl3) δ: 7.81 (d, J＝7.6 Hz, 1H), 7.71 (s,
1H), 7.34—7.43 (m, 7H), 7.29 (t, J＝7.2 Hz, 1H), 7.18
(dd, J＝2.4, 8.0 Hz, 1H), 7.13 (t, J＝7.2 Hz, 1H), 7.01
(d, J＝8.4 Hz, 2H), 6.10 (q, J＝6.4 Hz, 1H), 1.65 (d,
J＝6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 165.2,
157.4, 156.7, 141.6, 132.4, 129.9, 129.7, 128.6, 128.0,
calcd for C21H17ClO3Na [M＋Na]＋ 375.0758, found
375.0761.
1-(3-Nitrophenyl) ethyl 3-phenoxybenzoate (4f)
1H NMR (400 MHz, CDCl3) δ: 8.31 (s, 1H), 8.20 (d,
J＝8.4 Hz, 1H), 7.84 (d, J＝7.6 Hz, 1H), 7.77 (d, J＝
7.6 Hz, 1H), 7.73 (s, 1H), 7.57 (t, J＝8.0 Hz, 1H), 7.45
(t, J＝7.6 Hz, 1H), 7.39 (t, J＝7.6 Hz, 2H), 7.25 (dd,
J＝2.0, 8.4 Hz, 1H), 7.18 (t, J＝7.2 Hz, 1H), 7.05 (d,
J＝8.0 Hz, 2H), 6.19 (q, J＝6.4 Hz, 1H), 1.73 (d, J＝
6.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 165.1,
157.6, 156.6, 143.8, 132.2, 131.6, 130.0, 129.9, 129.7,
124.3, 123.9, 123.5, 123.0, 121.0, 119.7, 119.2, 72.0,
22.3; HRMS (ESI) calcd for C21H17NO5Na [M＋Na]＋
386.0999, found 386.0995.
126.1, 124.4, 123.8, 123.2, 119.8, 119.1, 73.2, 22.4;
＋
HRMS (ESI) calcd for C21H18O3Na [M ＋ Na]
341.1148, found 341.1147.
1-Phenylpropyl 3-phenoxybenzoate (4g) 1H
NMR (400 MHz, CDCl3) δ: 7.75 (d, J＝7.6 Hz, 1H),
7.64 (s, 1H), 7.18—7.34 (m, 8H), 7.11 (dd, J＝2.4, 8.0
Hz, 1H), 7.06 (t, J＝7.2 Hz, 1H), 6.94 (d, J＝8.0 Hz,
2H), 5.81 (t, J＝6.8 Hz, 1H), 1.82—2.02 (m, 2H), 0.87
(t, J＝7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ:
165.3, 157.5, 156.7, 140.5, 132.4, 129.9, 129.7, 128.4,
127.9, 126.5, 124.3, 123.8, 123.1, 119.7, 119.1, 78.2,
29.5, 10.0; HRMS (ESI) calcd for C22H20O3Na [M＋
Na]＋ 355.1305, found 355.1304.
1-(2-Bromophenyl)ethyl 3-phenoxybenzoate (4b)
1H NMR (400 MHz, CDCl3) δ: 7.88 (d, J＝7.6 Hz, 1H),
7.76 (s, 1H), 7.59 (d, J＝8.0 Hz, 1H), 7.54 (d, J＝7.6
Hz, 1H), 7.45 (t, J＝8.0 Hz, 1H), 7.40 (t, J＝7.6 Hz,
2H), 7.35 (t, J＝7.6 Hz, 1H), 7.25 (dd, J＝2.0, 8.4 Hz,
1H), 7.18 (t, J＝7.2 Hz, 2H), 7.07 (d, J＝8.0 Hz, 2H),
6.42 (q, J＝6.4 Hz, 1H), 1.68 (d, J＝6.8 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ: 164.9, 157.6, 156.6, 141.2,
133.0, 132.0, 130.0, 129.8, 129.2, 127.9, 126.8, 124.3,
123.9, 123.2, 121.8, 119.6, 119.2, 72.4, 21.3; HRMS
(ESI) calcd for C21H17BrO3Na [M＋Na]＋ 419.0253,
found 419.0255.
1-p-Tolylethyl 3-phenoxybenzoate (4h) 1H NMR
(400 MHz, CDCl3) δ: 7.84 (d, J＝7.6 Hz, 1H), 7.74 (s,
1H), 7.34—7.44 (m, 5H), 7.15—7.23 (m, 4H), 7.04 (d,
J＝8.0 Hz, 2H), 6.11 (q, J＝6.4 Hz, 1H), 2.38 (s, 3H),
1.67 (d, J＝6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ:
165.3, 157.4, 156.7, 138.7, 137.7, 132.4, 129.9, 129.7,
129.2, 126.1, 124.4, 123.7, 123.2, 119.8, 119.1, 73.2,
22.3, 21.2; HRMS (ESI) calcd for C22H20O3Na [M＋
Na]＋ 355.1305, found 355.1301.
1-(4-Methoxyphenyl)ethyl 3-phenoxybenzoate (4c)
1H NMR (400 MHz, CDCl3) δ: 7.82 (d, J＝7.6 Hz, 1H),
7.73 (t, J＝7.0 Hz, 1H), 7.36—7.44 (m, 5H), 7.20 (dd,
J＝1.6, 8.4 Hz, 1H), 7.15 (t, J＝7.2 Hz, 1H), 7.03 (d,
J＝7.6 Hz, 2H), 6.91 (d, J＝8.8 Hz, 2H), 6.08 (q, J＝
6.4 Hz, 1H), 3.83 (s, 3H), 1.67 (d, J＝6.8 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ: 165.3, 159.3, 157.4, 156.7,
133.7, 132.5, 129.9, 129.7, 127.6, 124.4, 123.7, 123.2,
119.8, 119.1, 113.9, 73.0, 55.3, 22.2; HRMS (ESI) calcd
for C22H20O4Na [M＋Na]＋ 371.1254, found 371.1254.
1-(4-(Trifluoromethyl)phenyl)ethyl-3-phenoxy-
benzoate (4d) 1H NMR (400 MHz, CDCl3) δ: 7.84 (d,
J＝7.6 Hz, 1H), 7.73 (s, 1H), 7.65 (d, J＝8.4 Hz, 2H),
7.55 (d, J＝8.4 Hz, 2H), 7.44 (t, J＝8.0 Hz, 1H), 7.39 (t,
J＝7.6 Hz, 2H), 7.24 (dd, J＝2.0, 8.0 Hz, 1H), 7.18 (t,
J＝7.2 Hz, 1H), 7.05 (d, J＝7.6 Hz, 2H),6.15 (q, J＝6.4
Cyclohexyl 3-phenoxybenzoate (4i) 1H NMR
(400 MHz, CDCl3) δ: 7.82 (d, J＝7.6 Hz, 1H), 7.72 (s,
1H), 7.36—7.44 (m, 3H), 7.20 (dd, J＝2.4, 8.0 Hz, 1H),
7.16 (t, J＝7.2 Hz, 1H), 7.04 (d, J＝7.6 Hz, 2H),
5.01—5.07 (m, 1H), 1.93—1.98 (m, 2H), 1.78—1.82
(m, 2H), 1.56—1.62 (m, 2H), 1.35—1.51 (m, 4H); 13C
NMR (100 MHz, CDCl3) δ: 165.4, 157.3, 156.8, 132.9,
129.9, 129.6, 124.3, 123.6, 123.0, 119.8, 119.0, 73.3,
31.6, 25.4, 23.6; HRMS (ESI) calcd for C19H20O3Na
[M＋Na]＋ 319.1305, found 319.1308.
Pentan-2-yl 3-phenoxybenzoate (4j) 1H NMR
(400 MHz, CDCl3) δ: 7.78 (d, J＝7.6 Hz, 1H), 7.68 (s,
1H), 7.33—7.41 (m, 3H), 7.17 (dd, J＝2.4, 8.4 Hz, 1H),
7.13 (t, J＝7.2 Hz, 1H), 7.01 (d, J＝7.6 Hz, 2H),
5.11—5.19 (m, 1H), 1.67—1.76 (m, 1H), 1.52—1.61
(m, 1H), 1.36—1.46 (m, 2H), 1.32 (d, J＝6.4 Hz, 2H),
0.93 (t, J＝7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ:
165.6, 157.3, 156.8, 132.8, 129.9, 129.6, 124.3, 123.7,
123.0, 119.8, 119.0, 71.8, 38.2, 20.0, 18.7, 14.0; HRMS
(ESI) calcd for C18H20O3Na [M ＋ Na] ＋ 307.1305,
found 307.1308).
Hz, 1H), 1.69 (d, J＝6.8 Hz, 3H); 13C NMR (CDCl3) δ:
2
165.1, 157.6, 156.6, 145.6, 131.9, 130.1 (t, JC F＝32.3
—
3
Hz), 129.9, 126.2, 125.6 (t, JC F＝3.7 Hz), 124.3,
—
1
124.0 (t, JC F＝270.5 Hz), 123.8, 123.4, 120.0, 119.1,
—
72.4, 22.4; HRMS (ESI) calcd for C22H17F3O3Na [M＋
Na]＋ 409.1022, found 409.1020.
1-(4-Chlorophenyl) ethyl 3-phenoxybenzoate (4e)
1H NMR (400 MHz, CDCl3) δ: 7.79 (d, J＝7.6 Hz, 1H),
7.69 (s, 1H), 7.31—7.42 (m, 7H), 7.19 (dd, J＝2.0, 8.0
Hz, 1H), 7.14 (t, J＝7.2 Hz, 1H), 7.01 (d, J＝8.0 Hz,
2H), 6.06 (q, J＝6.4 Hz, 1H), 1.63 (d, J＝6.8 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ: 165.2, 157.5, 156.6,
140.2, 133.7, 132.1, 129.9, 129.8, 128.8, 127.5, 124.3,
123.8, 123.3, 119.7, 119.1, 72.5, 22.3; HRMS (ESI)
Benzyl 2,6-dimethylbenzoate (4k)
1H NMR
(CDCl3) δ: 7.35 (d, J＝6.8 Hz, 2H), 7.24—7.30 (m, 3H),
7.08 (t, J＝7.6 Hz, 1H), 6.92 (d, J＝7.6 Hz, 2H), 5.27 (s,
2H), 2.19 (s, 6H); 13C NMR (CDCl3) δ: 169.8, 135.6,
4
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, XX, 1—5

A Novel Metal-free Reductive Esterification of N-Tosylhydrazones with Carboxylic Acids
135.0, 133.7, 129.4, 128.7, 128.6, 128.4, 127.6, 66.9,
19.7; HRMS (ESI) calcd for C16H17O2 [M ＋ H] ＋
241.1223, found 241.1226.
tolerable under the reaction conditions to afford the
corresponding esters with low to good yields.
4-Methoxybenzyl 2,6-dimethylbenzoate (4l) 1H
NMR (CDCl3) δ: 7.38 (d, J＝8.4 Hz, 2H), 7.15 (t, J＝
7.6 Hz, 1H), 6.99 (d, J＝7.6 Hz, 2H), 6.89 (d, J＝8.4 Hz,
2H), 5.30 (s, 2H), 3.80 (s, 3H), 2.25 (s, 6H); 13C NMR
(CDCl3) δ: 169.9, 159.8, 134.9, 133.8, 130.6, 129.3,
127.8, 127.5, 113.9, 66.6, 55.3, 19.7; HRMS (ESI) calcd
for C17H19O3 [M＋H]＋ 271.1329, found 271.1323.
4-Fluorobenzyl 2,6-dimethylbenzoate (4m) 1H
NMR (CDCl3) δ: 7.32—7.36 (m, 2H), 7.08 (t, J＝7.6
Hz, 1H), 6.97 (t, J＝8.4 Hz, 2H), 6.92 (d, J＝7.6 Hz,
2H), 5.23 (s, 2H), 2.17 (s, 6H); 13C NMR (CDCl3) δ:
169.7, 162.8 (d, 1JCF＝245.7 Hz), 135.0, 133.6, 131.6 (d,
Acknowledgement
The authors are thankful to the China Postdoctoral
Science Foundation (No. 2011M500096), and Natural
Scientific Research Innovation Foundation in Harbin
Institute of Technology (No. HIT.NSRIF 2010054). L.
Wu also would like to thank Harbin Institute of
Technology for startup financial support.
References
[1] Shao, Z.-H.; Zhang, H.-B. Chem. Soc. Rev. 2012, 41, 560.
[2] (a) Barluenga, J.; Moriel, P.; Valdés, C.; Aznar, F. Angew. Chem.,
Int. Ed. 2007, 46, 5587; (b) Rasolofonjatovo, E.; Tréguier, B.;
Provot, O.; Hamze, A.; Morvan, E.; Brion, J.-D.; Alami, M.
Tetrahedron Lett. 2011, 52, 1036.
3
4JCF＝3.1 Hz), 130.8 (d, JCF＝8.1 Hz), 130.7, 129.4,
127.6, 115.5 (d, 2JCF＝21.3 Hz), 66.1, 19.7; HRMS (ESI)
calcd for C16H15O2FNa [M＋Na]＋ 281.0948, found
281.0948.
[3] Tréguier, B.; Hamze, A.; Provot, O.; Brion, J.-D.; Alami, M.
Tetrahedron Lett. 2009, 50, 6549.
Isobutyl 2,6-dimethylbenzoate (4n) 1H NMR
(CDCl3) δ: 7.22 (t, J＝7.6 Hz, 1H), 7.07 (d, J＝7.6 Hz,
2H), 4.15 (d, J＝6.4 Hz, 2H), 2.36 (s, 6H), 2.04—2.14
(m, 1H), 1.04 (d, J＝6.4 Hz, 6H); 13C NMR (CDCl3) δ:
170.2, 134.8, 134.3, 129.2, 127.5, 71.3, 27.8, 19.7, 19.3;
HRMS (ESI) calcd for C13H19O2 [M＋H]＋ 207.1380,
found 207.1378.
[4] (a) Xiao, Q.; Xia, Y.; Li, H.; Zhang, Y.; Wang, J.-B. Angew. Chem.,
Int. Ed. 2011, 50, 1114; (b) Zhou, L.; Shi, Y.; Xiao, Q.; Liu, Y.-Z.;
Ye, F.; Zhang, Y.; Wang, J.-B. Org. Lett. 2011, 13, 968.
[5] Yao, T.; Hirano, K.; Satoh, T.; Miura, M. Angew. Chem., Int. Ed.
2011, 51, 775.
[6] Zhang, Z.-H.; Liu, Y.-Y.; Gong, M.-X.; Zhao, X.-K.; Zhang, Y.;
Wang, J.-B. Angew. Chem., Int. Ed. 2011, 49, 1139.
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2012, 124, 2943.
[8] Barluenga, J.; Tomás-Gamasa, M.; Aznar, F.; Valdés, C. Nature
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Conclusions
In conclusion, we have developed a novel method
for reductive coupling of N-tosylhydrazones with
carboxylic acids under metal-free conditions to access
esters. Various functional groups were found to be
[10] Ding, Q.-P.; Cao, B.-P.; Yuan, J.-J.; Liu, X.-J.; Peng, Y.-Y. Org.
Biomol. Chem. 2011, 9, 748.
(Lu, Y.)
Chin. J. Chem. 2012, XX, 1—5
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