Organic Letters
Letter
Table 5. FeCl -Catalyzed Halogenation Reactions of
Carboxylic Acids To Produce Amides
ORCID
3
a
Author Contributions
§
C.-H.L. and S.-M.L. contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by a grant from the National Research
Foundation of Korea (NRF) (Grant 2016-R-1-A2b4009460).
■
REFERENCES
■
(
1) Larock, R. C. Comprehensive Organic Transformations; Wiley-VCH:
Weinheim, 1999.
(2) (a) Norris, J. F.; Olmsted, A. W. Org. Synth. 1928, 8, 50. (b) Tesser,
R.; Santacesaria, E.; Di Serio, M.; Di Nuzzi, G.; Fiandra, V. Ind. Eng.
Chem. Res. 2007, 46, 6456−6465.
(3) (a) Caserio, F. F.; Dennis, G. E.; DeWolfe, R. H.; Young, W. G. J.
Am. Chem. Soc. 1955, 77, 4182−4183. (b) Bissinger, W. E.; Kung, F. E. J.
Am. Chem. Soc. 1947, 69, 2158−2163.
(4) (a) Appel, R. Angew. Chem., Int. Ed. Engl. 1975, 14, 801−811.
(
b) Appel, R.; Knoll, F.; Miche, W.; Morbach, W.; Wihler, H.-D.;
Veltmann, H. Chem. Ber. 1976, 109, 58−70.
5) Yasuda, M.; Yamasaki, S.; Onishi, Y.; Baba, A. J. Am. Chem. Soc.
004, 126, 7186−7187.
6) (a) Fujisawa, T.; Iida, S.; Sato, T. Chem. Lett. 1984, 13, 1173−1174.
b) Mukaiyama, T.; Shoda, S.-I.; Watanabe, Y. Chem. Lett. 1977, 6, 383−
86. (c) Benazza, M.; Uzan, R.; Beaupere, D.; Demailly, G. Tetrahedron
Lett. 1992, 33, 4901−4904. (d) Benazza, M.; Uzan, R.; Beaupere, D.;
(
2
(
(
3
̀
̀
Demailly, G. Tetrahedron Lett. 1992, 33, 3129−3132. (e) Denton, R. M.;
An, J.; Adeniran, B. Chem. Commun. 2010, 46, 3025−3027. (f) Cui, X.-
M.; Guan, Y.-H.; Li, N.; Lv, H.; Fu, L.-A.; Guo, K.; Fan, X. Tetrahedron
Lett. 2014, 55, 90−93. (g) Ajvazi, N.; Stavber, S. Tetrahedron Lett. 2016,
a
Reactions were carried out with 10 (2 mmol), 2a (2.4 mmol), 3a
(
0.06 mmol), TEA (4 mmol), and nucleophiles (3 mmol) in 1.0 mL of
5
7, 2430−2433. (h) Ayala, C. E.; Villalpando, A.; Nguyen, A. L.;
McCandless, G. T.; Kartika, R. Org. Lett. 2012, 14, 3676−3679.
i) Pouliot, M.-F.; Mahe, O.; Hamel, J.-D.; Desroches, J.; Paquin, J.-F.
b
CHCl at room temperature. Isolated yield.
3
(
́
Org. Lett. 2012, 14, 5428−5431. (j) Dai, C.; Narayanam, J. M. R.;
Stephenson, C. R. J. Nat. Chem. 2011, 3, 140−145. (k) Jaseer, E. A.;
Naidu, A. B.; Kumar, S. S.; Rao, R. K.; Thakur, K. G.; Sekar, G. Chem.
Commun. 2007, 867−869. (l) Tandiary, M. A.; Masui, Y.; Onaka, M.
Synlett 2014, 25, 2639−2643.
observed that reaction of 1q with 2a in the presence of 3a under
the standard reaction conditions generates the chloromethyl-
10
substituted benzoic acid derivative 4t in 88% isolated yield.
(
7) (a) Kelly, B. D.; Lambert, T. H. J. Am. Chem. Soc. 2009, 131,
This result suggests that the benzylic alcohol moiety is more
reactive with 2a than is the carbxylic acid group.
In conclusion, this investigation led to the development of a
simple, mild, and efficient method for halogenation of alcohols
and carboxylic acid. The process utilizes commercially available
α,α-dichlorodiphenylmethane as the halogenating agent and
1
3930−13931. (b) Hardee, D. J.; Kovalchuke, L.; Lambert, T. H. J. Am.
Chem. Soc. 2010, 132, 5002−5003. (c) Vanos, C. M.; Lambert, T. H.
Angew. Chem., Int. Ed. 2011, 50, 12222−12226.
(
8) (a) Nguyen, T. V.; Bekensir, A. Org. Lett. 2014, 16, 1720−1723.
(
1
b) Moerdyk, J. P.; Bielawski, C. W. Chem. - Eur. J. 2014, 20, 13487−
3490.
FeCl as the catalyst. In addition, the conditions used for this
3
(9) α,α-Dichlorodiphenylmethane (2a) is a colorless and odorless oil.
process avoid the use of toxic starting materials and the formation
of stoichiometric amounts of oxidized phosphine and noxious
byproducts.
Because this compound is generally stable but reacts with water to
generate HCl, be sure to handle with care.
(10) The reaction of 1q (2 mmol) with 2a (3 equiv) was carried out in
the presence of 3a (5 mol %) for 3 h to produce 4-(chloromethyl)
benzoyl chloride in 73% GC yield.
ASSOCIATED CONTENT
■
*
S
Supporting Information
1
AUTHOR INFORMATION
■
D
Org. Lett. XXXX, XXX, XXX−XXX