A catalyst-free protocol for direct oxidative esterification of alcohols and aldehydes

Article abstract of DOI:10.1016/j.tetlet.2014.07.124

A fast, simple, and efficient protocol for the direct conversion of alcohols and aldehydes to methyl ester has been developed using TsNBr₂without any catalyst. The one pot reaction proceeds in the presence of a base at room temperature in methanol, to produce the corresponding methyl ester in high yield within a short time.

Full text of DOI:10.1016/j.tetlet.2014.07.124

Accepted Manuscript
A catalyst-free protocol for direct oxidative esterification of alcohols and alde-
hydes
Kamal Krishna Rajbongshi, Manas Jyoti Sarma, Prodeep Phukan
PII:
S0040-4039(14)01310-0
DOI:
http://dx.doi.org/10.1016/j.tetlet.2014.07.124
TETL 44967
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
13 May 2014
31 July 2014
31 July 2014
Please cite this article as: Rajbongshi, K.K., Sarma, M.J., Phukan, P., A catalyst-free protocol for direct oxidative
esterification of alcohols and aldehydes, Tetrahedron Letters (2014), doi: http://dx.doi.org/10.1016/j.tetlet.
2014.07.124
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A catalyst-free protocol for direct oxidative
esterification of alcohols and aldehydes
Kamal Krishna Rajbongshi, Manas Jyoti Sarma, Prodeep Phukan*
TsNBr2,
TsNBr2,
K2CO3 ( 5 equiv)
O
O
K2CO3 ( 2 equiv)
R
OH
CH3CN-MeOH (5:1),
rt
75% - 88%
R
H
MeOH, rt
R
OCH3
78% - 91%

1
Tetrahedron Letters
jour nal homepage: w ww.elsevier. com
A catalyst-free protocol for direct oxidative esterification of alcohols and aldehydes
Kamal Krishna Rajbongshi, Manas Jyoti Sarma, Prodeep Phukan*
a Department of Chemistry, Gauhati University, Guwahati -781014, Assam, India; E-mail: pphukan@yahoo.com
ARTICLE INFO
ABSTRACT
Article history:
Received
A fast, simple and efficient protocol for the direct conversion of alcohols and aldehydes to
methyl ester has been developed using TsNBr2 without any catalyst. The one pot reaction
proceeds in presence of a base at room temperature in methanol, to produce the corresponding
methyl ester with high yield within a short time.
Received in revised form
Accepted
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
TsNBr2
Oxidation
Methyl Esterification
Alcohol
Aldehyde
Esters belong to a class of organic compounds which are widely
used in industry, medicine, synthetic chemistry and in biology.1
In particular, methyl esters have high synthetic value in terms of
its biological activity.1 Classically, methyl esters are generated
from carboxylic acid by treating with methanol under acidic or
basic conditions.2 Synthesis of methyl esters can also be achieved
by reacting diazomethane with carboxylic acid.3 Although direct
oxidative methyl esterification of alcohol is a convenient
approach, a limited method has been reported. Recently, Mao et
al. carried out methyl esterification of alcohol using TBHP as
oxidant at 120 °C in presence of a copper catalyst.4 Another
protocol was developed by Ishii et al. using acetone as acceptor
under the influence of [Cp*IrCl2]2 combined with 2-
(methylamino)ethanol as catalyst.5 Ruthenium catalyzed
hydrogen transfer process has also been used for methyl
esterification of alcohols.6 Some other metal catalysts based on
Pd7, Au8, Zn9, Rh10 have been developed for similar process. Use
of TCCA,11 iodine,12 hypervalent iodine (III)13 as oxidizing agent
were also reported for such processes. Very recently, Beller
TsNBr2,
K2CO3
O
O
TsNBr2, K2CO3 , rt
CH3CN-MeOH (5:1)
R
OH
R
H
R
OCH3
MeOH, rt
Scheme 1: Methyl esterification of alcohols and aldehydes
Initially, the reaction was examined by using m-nitrobenzyl
alcohol (1a). When 1a (1 mmol) was treated with TsNBr2 (2.5
mmol) and K2CO3 (2 mmol) in MeOH (2 mL) at room
temperature (25-30°C), methyl 3-nitro benzoate (2a) was
produced in 43% yield (Table-1, entry1) after 2h of reaction.
Yield could be improved up to 50 % by increasing the amount of
TsNBr2 to 2.7 mmol. Further reaction in 5 mL of methanol could
improve the yield to 65%. Next, we examined the reaction using
different amount of K2CO3. We observed that the use of 5 equiv
of base could improve both the yield and rate of the reaction.
Reaction yield was found to be 70% in 80 min of reaction (Table
1, entry 7). On further investigation by changing the solvent
system from methanol to a mixture of acetonitrile (2 mL) and
methanol (1 mL) gave better result with 87 % yield within 45
minutes (Table1, entry 8). Interestingly, when the reaction was
examined by reducing the volume of methanol to 0.4 mL, the rate
of reaction was found to increase. In this case, the reaction was
found to complete within 30 min with 88% yield of the
corresponding methyl ester (Table 1, entry 9). The reaction in
absence of base gave very poor yield of the product (Table 1,
entry 10).
developed
a heterogeneous cobalt catalyst for oxidative
esterification of alcohols.14 Thus, most of the methods reported
so far requires some drastic condition such as high temperature,
expensive metal as a catalyst and long reaction time. Therefore,
development of a methodology which proceeds rapidly under
mild reaction condition, without using metal catalyst is of high
demand. Recently, we found that N,N-dibromo-p-toluene-
sulfonamide (TsNBr2) is a very reactive and efficient reagent for
various organic transformations.15 In continuation of our work on
this particular reagent, we report herein a very simple and
efficient method of direct oxidative esterificaiton of alcohol and
aldehydes using TsNBr2 under mild condition (Scheme 1).

2
Tetrahedron
a
a
Table 1. Methyl esterification using TsNBr2
Table 2. Esterification of different alcohols using TsNBr2
O
O
TsNBr2, K2CO3
OH
1a
TsNBr2, Base,
Solvent, rt
OCH3
2a
R
OH
R
OCH3
CH3CN:MeOH (2:1), rt
NO2
NO2
TsNBr2
Solvent
(mL)
Base
(equiv)
K2CO3
Yields
(%)b
O
O
O
Entry
Time
(equiv)
OCH3
OCH3
OCH3
1
2
3
4
5
6
7
MeOH (2mL)
MeOH (2mL)
MeOH (2mL)
MeOH (4mL)
MeOH (5mL)
MeOH (5mL)
MeOH (5mL)
2.5
2h
2h
2h
2h
2h
43
50
51
55
65
65
70
O2N
(2)
NO2
K2CO3
(2)
2b, 1h, 78%
2.7
3.0
2.7
2.7
2.7
2.7
2a, 30min, 88%
2c, 35min, 85%
K2CO3
(2)
O
O
O
OCH3
OCH3
OCH3
K2CO3
(2)
H3CO
Br
2e, 1.5h, 80%
Br
K2CO3
(2)
2d, 1.5h, 84%
2f, 45min, 80%
K2CO3
(4)
80
O
min
80
O
O
K2CO3
(5)
OCH3
OCH3
OCH3
min
N
Cl
CH3CN-
MeOH (2:1)
(3 mL)
2i, 2.5h, 77%
2g, 2h, 79 %
K2CO3
(5)
45
2h, 2h, 78%
8
9
2.7
87
min
O
O
O
CH3CN-
OCH3
OCH3
3
OCH3
K2CO3
(5)
30
5
MeOH (5:1)
(2.4 mL)
2.7
88
min
2l, 2h, 77%
2k, 2h, 75%
2j, 1h, 84%
aReaction condition: TsNBr2 (2.7 mmol) , alcohol (1 mmol), K2CO3 (5 mmol),
CH3CN-MeOH (5:1, 2.4 mL)
CH3CN-
MeOH
‒
2.7
2.7
2.7
2.7
2.7
2.7
2.7
6h
27
77
80
57
57
55
61
10
(2:1) (3 mL)
CH3CN-
MeOH (2:1)
(3 mL)
We intended to extend the process to an alcohol bearing a
double bond. When reaction was carried out using cinnamyl
alcohol, corresponding 2-bromo-3-methoxy-3-phenylpropan-1-ol
was produced as the major product (Scheme 2). This may be due
to the fact that, TsNBr2 reacts with olefins very fast to produce
corresponding methoxy bromide.15a
DBU
(4)
2h
11
12
CH3CN-
MeOH (2:1)
(3 mL)
DBU
(4)
2h
CH3CN-
MeOH (2:1)
(3 mL)
Na2CO3
(5)
13
14
15
16
3h
OCH3
CH3CN-
MeOH (2:1)
(3 mL)
CH2OH
CH2OH
TsNBr2, K2CO3
KOH
(5)
2.5h
3h
1m
2m
Br
CH3CN-MeOH(2:1), rt
CH3CN-
MeOH (2:1)
(3 mL)
NaOH
(5)
Scheme 2: Reaction with cinnamyl alcohol.
Recently, oxidative methyl esterification of aldehyde has also
receiving a great deal of attention. Different metal catalysts have
been employed for direct oxidative methyl esterification of
aldehyde.16 Other reagents such as NHC,17 oxone,18a NaIO4,18b
H2O2,18c mCPBA,18d KI–TBHP,18e NBS-Pyridine,18f NIS18g and
CH3CN-
MeOH (2:1)
(3 mL)
(Et)2NH
(5)
3h
aReaction conditions. Alcohol (1 mmol), rt. bIsolated yields.
Thereafter, we examined the reaction with different bases (Table
1). Although DBU could produce similar yield after 2h of
reaction, addition of other bases such as Na2CO3, KOH, NaOH
and (Et)2NH could not improve the reaction to a better extent.
Finally, the use of 2.7 equiv of TsNBr2, 5 equiv of K2CO3 and 2.4
mL of a mixture of acetonitrile and methanol (5:1) was found to
be the best choice in terms of yield and reaction time.
12
I2 are also reported for oxidative esterification of aldehydes.
After successful completion of the reaction with alcohol the
process was extended to a variety of aldehydes and to our
expectation, the reaction occurred more rapidly with aldehyde
compared to alcohol. We have carried out the reaction with
aldehyde using 1.5 equiv of TsNBr2 with K2CO3 (2 equiv) as a
base in 5 mL of methanol. The reaction could be carried out even
without bases though the yield is low compared to that with
K2CO3. The results are summarized in Table 3. In most cases, the
reaction is very fast to produce the corresponding ester in
excellent yield. The reaction was further investigated using other
alcohols such as ethanol and n-propanol. In this case, the use of a
5:1 mixture of acetonitrile and alcohol produced maximum yield
(Table 3).
After optimizing the reaction condition, we have extended the
reaction to various alcohols which is summarized in the Table
2.19 It is observed that the rate of reaction is very fast for benzyl
alcohols with electron withdrawing group such as nitro benzyl
alcohol. However, in case of other aromatic alcohols and
aliphatic alcohols, the reaction requires about 2h for appreciable
yield.

3
Table 3. Oxidative esterification of aldehydea
Ahamed, A. P.; Al-Dhabi, N. A.; Thajuddin, N. RSC
Adv. 2012, 2, 11552-11556; (d) Alam, A.; Takaguchi,
Y.; Ito, H.; Yoshida, T.; Tsuboi, S. Tetrahedron 2005,
61, 1909-1918; (f) Yamanaka, K.; Jikei, M.; Kakimoto,
M.-a. Macromolecules 2000, 33, 6937-6944; (g)
Narkhede, N.; Patel, A. Ind. Eng. Chem. Res. 2013, 52,
13637-13644.
TsNBr2, K2CO3
MeOH (5mL), rt
O
O
R
OCH3
R
H
O
O
O
OCH3
2. (a) Otera, J. Chem. Rev. 1993, 93, 1449-1470; (b)
Shinada, T.; Hamada, M.; Miyoshi, K.; Higashino, M.;
Umezawa, T.; Ohfune, Y. Synlett 2010, 2141-2145;
(c) Srinivas, K. V. N. S.; Mahender, I.; Das, B.
Synthesis 2003, 2479-2482; (d) Bartoli, G.; Bosco, M.;
Carlone, A.; Dalpozzo, R.; Marcantoni, E.; Melchiorre,
P.; Sambri, L. Synthesis 2007, 3489-3496.
OCH3
OCH3
O2N
NO2
2c, 25min, 88%
2b, 15 min 78%,
2a, 15min, 91%
O
O
O
OCH3
OCH3
OCH3
3. (a) Black, T. H. Aldrichimica Acta 1983, 16, 3;
(b) Mastronardi, F.; Gutmann,B.; Kappe, C.O. Org.
Lett. 2013, 15, 5590-5593
H3CO
Br
Br
2e, 45min, 85%
2f, 45min, 85%
2d, 1h, 84%
4. Zhu, Y.; Yan, H.; Lu, L.; Liu, D.; Rong, G.; Mao, J. J.
Org. Chem. 2013, 78, 9898-9905
5. Yamamoto, N.; Obora, Y.; Ishii, Y. J. Org. Chem.
2011, 76, 2937-2941.
O
O
O
OCH3
OCH3
OCH3
N
Cl
6. (a) Owston, N. A.; Parker, A. J.; Williams, J. M. J.
Chem. Commun. 2008, 624-625; (b) Murahashi, S.;
Naota, T.; Ito, K.; Maeda, Y.; Taki, H. J. Org. Chem.
1987, 52, 4319-4327.
2i, 2.h, 79%
2h, 2h, 79%
2g, 1h, 81%
O
O
O
7. (a) Gowrisankar, S.; Neumann, H.; Beller, M. Angew.
Chem. Int. Ed. 2011, 50, 5139-5143; (b) Bai, X.-F.; Ye,
F.; Zheng, L.-S.; Lai, G.-Q.; Xia, C.-G.; Xu, L.-W.
Chem. Commun. 2012, 48, 8592-8594; (c) Liu, C.;
Wang, J.; Meng, L.; Deng, Y.; Li, Y.; Lei, A. Angew.
Chem. Int. Ed. 2011, 50, 5144-5148
OCH3
OCH3
OCH3
N
H3CO
OCH3
4a, 1h, 83%
4c, 1h, 80%
4b, 1.5h, 85%
O
O
O
8. (a) Miyamura, H.; Yasukawa, T.; Kobayashi, S. Green
Chem. 2010, 12, 776-778; (b) Su, F.-Z.; Ni, J.; Sun, H.;
Cao, Y.; He, H.-Y.; Fan, K.-N. Chem. Euro. J. 2008,
14, 7131-7135; (c) Wang, L.; Li, J.; Dai, W.; Lv, Y.;
Zhang, Y.; Gao, S. Green Chem. 2014, 16, 2164-2173.
9. Wu, X.-F. Chem. Euro. J. 2012, 18, 8912-8915.
10. Zweifel, T.; Naubron, J.-V.; Grützmacher, H. Angew.
Chem. Int. Ed. 2009, 48, 559-563
OCH3
OCH3
3
OCH3
5
2j, 40min, 88%
2l, 1.5h, 81%
2k, 1.5h, 84%
O
O
O
O
O
O
Br
4e, 1h 79% b
NO2
NO2
4f, 2h, 78% b
11. Hiegel, G. A.; Gilley, C. B. Synth. Commun. 2003, 33,
2003-2009.
4d, 1h, 80% b
12. Mori, N.; Togo, H. Tetrahedron 2005, 61, 5915-5925.
13. Tohma, H.; Maegawa, T.; Kita, Y. Synlett 2003, 0723-
0725.
aReaction Condition : TSNBr2 (1.5 mmol), aldehyde (1 mmol), K2CO3 (2
mmol), MeOH (5 mL), rt; b alcohol (0.4 mL), CH3CN (2 mL).
14. Jagadeesh, R. V.; Junge, H.; Pohl, M.-M.; Radnik, J.;
Brückner, A.; Beller, M. J. Am. Chem. Soc. 2013, 135,
10776-10782.
In summary, we have developed a very simple, efficient and
fast method for the direct synthesis of methyl ester from both
alcohol as well as aldehyde using TsNBr2 in presence of K2CO3
as base. The reaction could be extended to other alcohols such as
ethanol and n-propanol also. The reaction is convenient as it
proceeds at room temperature within a very short time with high
yield.
15. (a) Phukan, P.; Chakraborty, P.; Kataki, D. J. Org.
Chem. 2006, 71, 7533-7537; (b) Saikia, I.; Phukan, P.
Tetrahedron Lett. 2009, 50, 5083-5087; (c) Saikia, I.;
Chakraborty, P.; Phukan, P. ARKIVOC, 2009 (xiii), 281
(d) Saikia, I.; Kashyap, B.; Phukan, P. Synth. Commun.
2010, 40, 2647-2652; (e) Saikia, I.; Kashyap, B.;
Phukan, P. Chem. Commun. 2011, 47, 2967-2969; (f)
Borah, A. J.; Phukan, P. Chem. Commun. 2012, 48,
5491-5493; (g) Saikia, I.; Rajbongshi, K. K.; Phukan, P.
Tetrahedron Lett. 2012, 53, 758-761; (h) Borah, A. J.;
Phukan, P. Tetrahedron Lett. 2012, 53, 3035-3037. (i)
Rajbongshi, K. K.; Phukan, P. Tetrahedron Lett. 2014,
55, 1877-1878.
Acknowledgement: Financial support from DST (Grant No.
SR/S1/OC-43/2011) is gratefully acknowledged.
References and notes:
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4
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19. General Procedure for synthesis of methyl ester: To
a solution of alcohol (1mmol) in a mixture of MeCN
and MeOH (5:1, 2.4 mL) was added TsNBr2 (2.5 mmol)
and K2CO3 (5 mmol) and stirred at room temperature.
After completion of the reaction (TLC) sodium
thiosulfate was added and the reaction mixture was
stirred for 10 min. The reaction mixture was extracted
in diethyl ether and hexane (1:1), dried (Na2SO4) and
concentrated. Purification of the crude product by flash
chromatography on silica gel (230-400mesh) with
petroleum ether –EtOAc as eluent gave the pure
product.
In case of methyl ester synthesis from aldehydes,
reaction was carried out using 1.5 mmol of TsNBr2 and
2 mmol of K2CO3 was used for 1 mmol of substrate.
For methyl ester synthesis, methanol (5 mL) was used
as solvent and for other alkyl ester synthesis 5:1
mixture of MeCN-ROH (2.4 mL) was used as the
reaction medium. Work-up procedure remains same.

5
Highlight
Title of the manuscript:
A
catalyst-free
protocol for direct
oxidative
esterification
of
alcohols under mild
condition
Authors: Kamal Krishna Rajbongshi, Manas Jyoti
Sarma and Prodeep Phukan
1. Fastest method for direct esterification of
alcohols.
2. The process does not require any catalyst.
3. This protocol is simple, mild and high
yielding.
4. Applicable for both benzylic and aliphatic
alcohols.
5. Extended for direct
aldehydes.
esterificaiton of