Synthesis of α-Chloromethyl Ketones by Iron-catalyzed Hydration Reaction of Alkynyl Chlorides†

doi:10.7503/cjcu20140400

Abstract

Abstract:

α-Chloro-methyl ketones are among the most versatile intermediates in organic synthesis, and their high reactivity makes them prone to react with a large number of nucleophiles to provide a variety of useful compounds. Hydration of alkynes has emerged as a powerful method for synthesizing carbonyl compounds because of its atom efficiency and its environmental advantages. A novel iron-catalyzed hydration reaction of alkynyl chlorides to synthesize α-chloro-methyl ketones was developed. The influences of catalyst, acid, reaction temperature and solvent were investigated, the result indicated that the reaction proceeded smoothly to give the corresponding products in good yields using 5%(molar fraction) FeCl₃·6H₂O, 20%(molar fraction) MsOH and H₂O in 1,2-dichloroethane(DCE) for 3 h at 80 ℃. The structure of α-chloromethyl ketone derivatives was confirmed by IR, ¹H NMR, ¹³C NMR and MS. The reaction method with its advantages of simple procedure, mild reaction conditions and high yield provides a novel valuable approach to α-chloro-methyl ketones.

Key words: Iron catalysis, Alkynyl chloride, α-Chloromethyl ketone, Hydration reaction

CLC Number:

O621

TrendMD:

YI Weiguo, YAN Dong, WU Chao, LAN Lixin. Synthesis of α-Chloromethyl Ketones by Iron-catalyzed Hydration Reaction of Alkynyl Chlorides^†[J]. Chem. J. Chinese Universities, 2014, 35(12): 2563.

Figures/Tables 3

References 21

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Compd.	MS(ES⁺), m/z(ref.)	Compd.	MS(ES⁺), m/z(ref.)	Compd.	MS(ES⁺), m/z(ref.)
2a	154.0(154.0^[18])	2g	168.0(168.0^[20])	2m	164.1(164.1^[20])
2b	168.0(168.0^[18])	2h	240.1(240.1^[19])	2n	303.1(303.1^[20])
2c	188.0(188.0^[18])	2i	250.1(250.1^[19])	2o	279.1(279.1^[20])
2d	231.9(231.9^[18])	2j	214.0(214.0^[19])	2p	160.1(160.1^[19])
2e	182.0(182.0^[18])	2k	304.1(304.1^[19])	2q	212.0(212.0^[20])
2f	218.1(218.1^[19])	2l	192.1(192.1^[19])	2r	262.1(262.1^[20])

Compd.	MS(ES⁺), m/z(ref.)	Compd.	MS(ES⁺), m/z(ref.)	Compd.	MS(ES⁺), m/z(ref.)
2a	154.0(154.0^[18])	2g	168.0(168.0^[20])	2m	164.1(164.1^[20])
2b	168.0(168.0^[18])	2h	240.1(240.1^[19])	2n	303.1(303.1^[20])
2c	188.0(188.0^[18])	2i	250.1(250.1^[19])	2o	279.1(279.1^[20])
2d	231.9(231.9^[18])	2j	214.0(214.0^[19])	2p	160.1(160.1^[19])
2e	182.0(182.0^[18])	2k	304.1(304.1^[19])	2q	212.0(212.0^[20])
2f	218.1(218.1^[19])	2l	192.1(192.1^[19])	2r	262.1(262.1^[20])

Entry		Yield^b(%)	Entry		Yield^b(%)
1	2b	90	10	2k	83
2	2c	95	11	2l	85
3	2d	93	12	2m	81
4	2e	82	13	2n	81
5	2f	88	14	2o	78
6	2g	91	15	2p	90
7	2h	85	16	2q	88
8	2i	88	17	2r	84
9	2j	87

Entry		Yield^b(%)	Entry		Yield^b(%)
1	2b	90	10	2k	83
2	2c	95	11	2l	85
3	2d	93	12	2m	81
4	2e	82	13	2n	81
5	2f	88	14	2o	78
6	2g	91	15	2p	90
7	2h	85	16	2q	88
8	2i	88	17	2r	84
9	2j	87