K2CO3-promoted formation of aryl esters from primary aryl amides by the acyl-acyl exchange process

Article abstract of DOI:10.1039/c6ob00187d

A new acyl-acyl exchange reaction has been developed for the formation of aryl esters from primary aryl amides. The reaction could occur under mild reaction conditions with catalytic quantities of K₂CO₃, and could afford moderate to good yields of the desired products.

Full text of DOI:10.1039/c6ob00187d

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DOI: 10.1039/C6OB00187D
Organic & Biomolecular Chemistry
COMMUNICATION
K2CO3-Promoted formation of aryl esters from primary aryl
amides by acyl-acyl exchange process
Received 00th January 20xx,
Accepted 00th January 20xx
Yongjun Bian*, Xingyu Qu
DOI: 10.1039/x0xx00000x
www.rsc.org/
Previous works:
A new acyl-acyl exchange reaction has been developed for the
formation of aryl esters from primary aryl amides. The reaction
could occur under mild reaction conditions with the catalytic
quantities of K2CO3, and could afford moderate to good yields of
desired products.
O
O
O
O
Pd (OAc)2/dppe
+
R2
R1
OR1
(1)
(2)
R2
O
H
N
O
OR1
O
Zr(NMe2)4
+
R1
NR2R3
R6
NR4R5
+
NR4R5
R6
NR2R3
Esters are one of the most prevalent and important functional
groups abundant in both naturally occurring and synthetic
organic compounds.1 Conventional methods for preparation of
the esters use carboxylic acids and their derivatives (mainly
acid chloride or acid anhydride) as the acylating reagents
through the condensation with alcohols. However, this
method is commonly limited due to the unstability of
carboxylic acid derivatives. Another protocol is the
transesterification between esters and alcohols in the
This work:
O
transition metal-free
O
O
+
R3
NH2
R1
OR2
R3
OR2
(3)
Scheme 1 Acyl-acyl exchange reaction
amides and esters. To the best of our knowledge, no relevant
work was reported. Herein, we want to report a acyl-acyl
exchange reaction between aryl esters and primary aryl
amides (Scheme 1, Eq 3). The reaction is general, efficient, and
environmentally benign for the synthesis of various aryl esters.
Initially, the inexpensive copper salts were used as the
catalysts to attempt the acyl-acyl exchange reactions between
aryl esters and primary aryl amides. when a toluene solution
containing 0.25mmol of 2-naphthyl pivalate 1a, 0.5 mmol of 4-
methoxybenzamide 2a, 0.01 mmol of CuI and 0.02 mmol of
1,10-phenanthroline was refluxed in the presence of 2 equiv of
K3PO4·3H2O for 12 h. (See SI). Pleasingly, a small amount of
acyl-acyl exchange product 3aa was observed. After further
screening of various factors, we discovered the base was
extremely crucial. If no base was added to the solution, no
desired product was generated. Surprisingly, the reaction
could be promoted smoothly only using the base without
transition metal catalysts. Subsequently, several common
bases were screened for the optimal reaction condition in
absence of any transition metal, and the results are showed in
Table 1(for details, see SI). Among them, K3CO3 proved to be
best to give the acyl-acyl exchange product 3aa in 60% yield
(Table 1, entry 4). Although, t-BuOK and t-BuOLi were also
effective for this transformation, only the low yields of desired
products were isolated (Table 1, entries 1-2). When LiOAc,
NaOAc and KF were used as the bases, no product was
obtained (Table 1, entries 5-7). Solvents had a very important
influence on the reaction. Other solvents, such as 1,4-dioxane
or DMF other than toluene, were ineffective on this exchange
presence of strong acids or bases.2, 3 Over the past decades,
4
several new Lewis acid catalysts, such as Y5(OiPr)13O
,
Zn4(OCOCF3)6O 5, La(OiPr)3 6, Co2(OCOtBu)2 and NHC (N-
heterocyclic carbine)8, were developed for transesterification.9
Recently, a challenging and underdeveloped methodology has
also been explored for the synthesis of esters, in which the
7
notorious stable amides were cleaved by alcohols to give
10, 11
esters.
For example, Mashima et al demonstrated Zinc-
catalyzed esterification of β-hydroxyethylamides through
10a
amide bond cleavage by alcohol.
The acyl-acyl exchange
reaction may be a potentially valuable progress for the
preparation of esters as well. For example, Huang et al
reported Pd-catalyzed acyl-acyl exchange between N-
heterocyclic aromatic esters and aldehydes for the synthesis of
esters. (Scheme 1, Eq 1).12a, 13 In 2009, Gellman et al achieved
acyl-acyl exchange between amides and amides using Zr- and
Ha-amido complexes as the catalyst (Scheme 1, Eq 2). 14 These
works inspired us to consider acyl-acyl exchange between
College of Chemistry and Chemical Engineering, Jinzhong University, Yuci 030619,
P. R. of China
E-mail: yjbian2013@jzxy.edu.cn
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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reaction (Table 1, entries 8-9, for details, see SI). In addition, Table 2. Various Oxygen Functional Groups a
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DOI: 10.1039/C6OB00187D
O
O
the amount of the base was also investigated. The better
OR
K2CO3 (20 mol%)
O
NH2
+
result was afforded only using catalytic amount of K2CO3,
possibly due to the decomposition of 2-naphthyl pivalate 1a
and product ester in the presence of large excess of base
(Table 1, compare entries 4 with 11). Obviously, we have
developed a new transition metal-free catalytic method for
the synthesis of aryl esters.
toluene, 120℃
O
O
1a, 1A-1G
2a
3aa
Entry
R
Yield (%) b
1
2 c
3
Piv (1a)
PA (1A)
Ac (1B)
Bz (1C)
82
58
46
35
53
12
0
We also examined the possibility of activating alternative
acyl C-O bonds, which have been successfully exchanged in the
presence of catalytic amount of K2CO3 (Table 2). PA naphthol
derivative showed the similar reactive as privalate 1a under
the optimized reaction condition and resulted in a 58% yield of
aryl ester 3aa (Table 2, entry 2). In the reaction of 2-naphthyl
acetate and benzoate, 46% and 35% yields of the desired
products were obtained, respectively (Table 2, entries 3-4).
Furthermore, the benzamide as the corresponding exchange
product was isolated in the reaction of 2-naphthyl benzoate
with 4-methoxybenzamide, which confirmed that this reaction
was accomplished through the acyl-acyl exchange process (for
details see SI). Five member heterocyclic 2-furoyl and 2-
thenoyl naphthol were also attempted, yields were
substantially less than with privalate 1a (Table 2, entries 5-6).
Notably, Sulfonyl naphthol derivative and 2-Napthylmethyl
ether were not suitable substrates for this acyl-acyl exchange
reaction and failed to react at all (Table 2, entries 7-8).
4
5
2-Furoyl (1D)
2-Thenoyl (1E)
Ts (1F)
6
7
8
Me (1G)
0
a Condition
(2.0 mL), 120
：1
℃
(0.25 mmol), 2a (0.50 mmol), K2CO3 (20 mol %), toluene
, 12h. b Isolated yield. C PA = 2-Pyridinecarboxyl.
benzene rings of phenolic esters had a certain effect on the
yields of the desired products. When The substituents were
strong electron-withdrawing groups, the reaction was either
difficultly promoted or prevented. For example, when 4-
acetylphenyl pivalate 1f was used as the starting material to
react with 4-methoxybenzamide, the desired exchanged
product 3fa was obtained only in 39% yield. Notably, no
desired product 3ka was isolated when 4-nitrophenyl pivalate
with a stronger electron-withdrawing group was used. The
position of the substituents on the benzene rings of phenolic
esters had effects on the reaction yields. When the
substituents were located at the meta-position, the yields
were decreased significantly (scheme 1, compare 3ca with 3ea
Under the optimized condition in our hand (Table1, entry
11), the scope of phenolic ester derivatives were explored to
examine the generality of this acyl-acyl exchange reaction.
Various desired aryl esters were formed in satisfied yields
(scheme 1). The results indicated that the reaction could
tolerate sorts of functional groups, such as methoxyl, chloro,
bromo, fluoro, nitro and acetyl groups. The substituents on the
O
O
R
R
OPiv
K2CO3(20 mol%)
O
Table 1. Optimization of the acyl-acyl exchange Reaction Condition a
NH2
+
toluene, 120℃
O
O
O
O
O
O
base
1
2
3
O
NH2
+
O
solvent, 120℃
O
O
O
O
O
1a
Entry
1
2a
3aa
O
O
Base.
Solvent
toluene
toluene
toluene
toluene
toluene
toluene
toluene
1,4-dioxane
DMF
Yield (%) b
O
O
O
3ba 73%
3aa 82%
3ca 74%
t-BuOLi
t-BuOK
52
33
O
O
O
2
O
O
O
3
K3PO4
·
3H2O
18
O
O
O
O
3ea 61%
3fa 39%
4
K2CO3
LiOAc
NaOAc
KF
60
3da 75%
O
O
5
trace
0
O
O
O
6
O
O
O
Cl
O
O
7
0
Br
F
3ga 76%
3ia 72%
3ha 73%
8
K2CO3
K2CO3
K2CO3
K2CO3
0
O
O
O
O
9
< 5
72 c
82 d
O
O
O
10
11
toluene
toluene
O
O2N
O
3la 74% b
3ja 54%
3ka 0%
Scheme 1. K2CO3-Promoted acyl-acyl exchange reaction for the
synthesis of the desired products . A mixture of (0.25 mmol), 4-
methoxybenzamide (0.50 mmol) and K2CO3 (20 mol%) in toluene was
stirred at 120 for 12 h; Yields of isolated products are given. Butyl
picolinate was used as the substrate.
a Condition
(2.0 mL), 120
mol % of K2CO3 was used.
：
1a (0.25 mmol), 2a (0.50 mmol), base (2equiv), solvent
, 12h. b Isolated yield. c 1 equiv of K2CO3 was used. d 20
3
1
2
℃
b
℃
2 | Org. Biomol. Chem., 2016, 00, 1-3
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Notes and references
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DOI: 10.1039/C6OB00187D
R
O
1
(a) R. Larock, In Comprehensive Organic Transformations,
R
OPiv
K2CO3(20 mol%)
O
NH2
2nd ed.; Wiley-VCH: New York, 1999. (b) J. Otera, In
Esterification; Wiley-VCH: Weinheim, 2003. (c) J. Otera, J.
Nishikido, Esterification; Wiley-VCH: Weinheim, 2010.
Some reviews on the transesterification, see: (a) G. A. Grasa,
R. Singh, S. P. Nolan, Synthesis. 2004, 971. (b) J. Otera, Acc.
Chem. Res. 2004, 37, 288.
+
toluene, 120℃
O
1a, 1b
2
3
2
3
Cl
O
O
O
O
3ab 81%
O
Some selected examples about the transesterification
between esters and alcohols in the presence of strong acids
or bases, see: (a) J. Otera, N. Danoh, H. Nozaki, J. Org. Chem.
1991, 56, 5307. (b) B. C. Ranu, P. Dutta, A. Sarkar, J. Org.
Chem. 1998, 63, 6207. (c) P. Ilankumaran, J. G. Verkade, J.
Org. Chem. 1999, 64, 3086. (d) P. Ilankumaran, J. G. Verkade,
J. Org. Chem. 1999, 64, 9063.
O
3ad 80% (68% b
)
3ac 82%
N
Br
O
O
O
O
O
O
3af 0%
3bg 0%
3be 72%
4
5
M.-H. Lin, T. V. RajanBabu, Org. Lett. 2000, 2, 997.
Scheme 2. Scope of the primary amides. Yields of isolated products are
given. b The naphthalen-2-yl picolinate was used as the substrate.
(a) T. Iwasaki, Y. Maegawa, Y. Hayashi, T. Ohshima, K.
Mashima, J. Org. Chem. 2008, 73, 5147. (b) T. Ohshima, T.
Iwasaki, Y. Maegawa, A. Yoshiyama, K. Mashima, J. Am.
Chem. Soc. 2008, 130, 2944. (c) T. Iwasaki, K. Agura, Y.
Maegawa, Y. Hayashi, T. Ohshima, K. Mashima, Chem. Eur. J.
2010, 16, 11567. (d) Y. Maegawa, T. Ohshima, Y. Hayashi, K.
or 3ja). The ortho-substituted aryl esters afforded the lower
yields of products possibly due to the large steric hindrance. A
heterocyclic aromatic ester was also tried and suitable for this
acyl-acyl exchange reaction, and could give rise to the desired
product 3la in a satisfied yield. When the unprotected 2-
naphthol was used instead of 2-naphthyl pivalate under the
standard reaction conditions, no desired product was
observed (see SI).
In another set of experiments, we selected various primary
amides as the acyl reagents to check this methodology
(Scheme 2). Several popular substituents, such as methyl,
chloro, and bromo groups, were very well compatible under
the optimized condition, and almost had no effect on the
yields of the desired acyl-exchanged products. Obviously,
when nicotinamide was used as the reactive substrate, no
desired product 3af was obtained possibly because of strong
electron-withdrawing nature of the pyridine. In addition,
aliphatic amide did not accomplish this transformation
(Scheme 2, 3bg). Other amides, such as secondary and tertiary
amides other than primary amides, were not applicable for the
current conditions (see SI).
Agura, T. Iwasaki, K. Mashima, ACS Catal. 2011, 1, 1178.
6
7
8
M. Hatano, Y. Furuya, T. Shimmura, K. Moriyama, S. Kamiya,
T. Maki, K. Ishihara, Org. Lett. 2011, 13, 426.
Y. Hayashi, S. Santoro, Y. Azuma, F. Himo, T. Ohshima, K.
Mashima, J. Am. Chem. Soc. 2013, 135, 6192.
some selected example using NHC as the catalysts for
transesterification, see: (a) G. A. Grasa, R. M. Kissling, S. P.
Nolan, Org. Lett. 2002, 4, 3583. (b) R. Singh, R. M. Kissling, M.
A. Letellier, S. P. Nolan, J. Org.Chem. 2004, 69, 209. (c) C.
Munro-Leighton, S. A. Delp, E. D. Blue, T. B. Gunnoe,
Organometallics, 2007, 26, 1483. (d) T. Q. Zeng, G. H. Song, C.
J. Li, Chem. Commun. 2009, 6249.
9
some selected other Lewis acid catalysts for
transesterification, see: (a) J. W. J. Bosco, A. K. Saikia, Chem.
Commun. 2004, 1116. (b) A. Solhy, J. H. Clark, R. Tahir, S.
Sebti, M. Larzek, Green Chem, 2006,
8 , 871. (c) M. S. Abase,
E. Akbarzadeh, S. Roholah, M. M. Mojtahedi, Monatsh Chem.
2010, 141, 757. (d) M. Tamura, S. M. A. Siddiki, K. I. Shimizu,
Green Chem , 2013, 15 , 1641.
10 (a) Y. Kita, Y. Nishii, T. Higuchi, K. Mashima, Angew. Chem.,
Int. Ed. 2012, 51, 5723. (b) Y. Kita, Y. Nishii, A. Onoue, K.
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ö
hmer,
Conclusions
S. Mundinger, S. Br se, W. Bannawarth, Angew. Chem., Int.
ä
Ed. 2011, 50, 6175. (e) J. Aub
51, 3063.
é, Angew. Chem., Int. Ed. 2012,
In conclusion, we have explored an effective method for the
formation of aryl esters by acyl-acyl exchange reactions only
utilizing catalytic quantities of K2CO3 without the use of any
transition metal catalysts. The reaction could proceed
smoothly under mild conditions to give the desired aryl esters
in satisfactory yields, and tolerate various functionalities, such
as methoxy, fluoro, chloro and bromo groups. Further studies
on expanding the scope of the substrates and on detailed
reaction mechanism are in progress.
11 The amides was cleaved by amine to give carboxamides, see:
(a) C. L. Allen, B. N. Atkinson, J. M. J. Williams, Angew. Chem.
Int. Ed. 2012, 51, 1383. (b) M. Zhang, S. Imm, S. Bähn, L.
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12 (a) Y.-S. Bao, C.-Y. Chen, Z.-Z. Huang, J. Org.Chem. 2012, 77
8344. (b) S. Kumar, R. Vanjari, T. Guntreddi, K. N. Singh, RSC
Adv. 2015, , 9920.
,
5
13 Some selected examples about aldehydes as the acylating
reagents, see: (a) O. Baslé, J. Bidange, Q. Shuai, C. J. Li, Adv.
Synth. Catal. 2010, 352, 1145. (b) Q. Shuai, L. Yang, X. Y. Guo,
O. Baslé, C. J. Li, J. Am. Chem. Soc. 2010, 132, 12212. (c) Z. Liu,
J. Zhang, S. Chen, E. Shi, Y. Xu, X. Wan, Angew. Chem., Int. Ed.
2012, 51, 3231. (d) Y. J. Bian, C. Y. Chen, Z. Z. Huang, Chem.-
Eur. J. 2013, 19, 1129.
Acknowledgements
This work was supported by the Scientific and Technological
Innovation Programs of Higher Education Institutions in Shanxi
( NO. 2015176), the Doctoral Scientific Research Foundation of
Jinzhong university(NO.bsjj2015213 and NO.bsjj2015214).
14 N. A. Stephenson, J. Zhu, S. H. Gellman, S. S. Stahl, J. Am.
Chem. Soc. 2009, 131, 10003.
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