Mild and Regioselective N-Alkylation of 2-Pyridones in Water

被引：51

作者：

Hao, Xin ^{[1
]}

Xu, Zhongmiao ^{[1
]}

Lu, Hongfu ^{[1
]}

Dai, Xuedong ^{[1
]}

Yang, Ting ^{[1
]}

Lin, Xichen ^{[1
]}

Ren, Feng ^{[1
]}

机构：

[1] GlaxoSmithKline, Res & Dev, Shanghai 201203, Peoples R China

来源：

ORGANIC LETTERS | 2015年 / 17卷 / 14期

关键词：

HETEROCYCLIC AMBIDENT ANIONS; O-ALKYLATION; ROOM-TEMPERATURE; PYRIDONES; N-ALKYL-2(1H)-PYRIDONES; 2-ALKOXYPYRIDINES; IODOBENZENES; CHEMISTRY; ARYLATION; CATALYSIS;

D O I：

10.1021/acs.orglett.5b01628

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A mild and regioselective N-alkylation reaction of 2-pyridones in water has been developed. Tween 20 (2% w/w) was added to create a micellar system for improved solubility of starting materials, which leads to enhanced reaction rates. The protocol demonstrated a wide substrate scope with good isolated yield's (40-94%) for all of the 24 examples evaluated. High regioselectivity favoring N-alkylation over O-alkylation was observed for benzyl halides (>5:1), primary alkyl halides (>6:1), and bulky and less reactive secondary alkyl halides (>2.4:1).

引用

页码：3382 / 3385

页数：4

共 41 条

[1] A PYRIDINE ALKALOID FROM CEROPEGIA-JUNCEA [J].

ADIBATTI, NA ;

THIRUGNANASAMBANTHAM, P ;

KULOTHUNGAN, C ;

VISWANATHAN, S ;

KAMESWARAN, L ;

BALAKRISHNA, K ;

SUKUMAR, E .

PHYTOCHEMISTRY, 1991, 30 (07) :2449-2450

[2] Origins, current status, and future challenges of green chemistry [J].

Anastas, PT ;

Kirchhoff, MM .

ACCOUNTS OF CHEMICAL RESEARCH, 2002, 35 (09) :686-694

[3]

[Anonymous], 2007, ORGANIC REACTIONS WA

[4] Rapid microwave-promoted Suzuki cross coupling reaction in water [J].

Bai, L ;

Wang, JX ;

Zhang, YM .

GREEN CHEMISTRY, 2003, 5 (05) :615-617

[5]

BALAVOINE G, 1979, TETRAHEDRON LETT, P3949

[6] THE PREPARATION OF N-ALKYL-2(1H)-PYRIDONES BY THE REACTION OF AMINES WITH A DERIVATIVE OF 3-(2-PYRIDYL)PROPANE-1,2-DIOL [J].

BLOCK, MH .

TETRAHEDRON LETTERS, 1992, 33 (52) :8149-8150

[7] Regioselective synthesis of N-alkyl pyridones [J].

Bowman, WR ;

Bridge, CF .

SYNTHETIC COMMUNICATIONS, 1999, 29 (22) :4051-4059

[8] Ambident Reactivities of Pyridone Anions [J].

Breugst, Martin ;

Mayr, Herbert .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2010, 132 (43) :15380-15389

[9] ALKYLATIONS OF HETEROCYCLIC AMBIDENT ANIONS .4. ALKYLATION OF 5-CARBETHOXY-2-PYRIDONE AND 5-NITRO-2-PYRIDONE SALTS [J].

CHUNG, NM ;

TIECKELM.H .

JOURNAL OF ORGANIC CHEMISTRY, 1970, 35 (08) :2517-&

[10] N-ALKYLATION VS O-ALKYLATION IN THE MITSUNOBU REACTION OF 2-PYRIDONE [J].

COMINS, DL ;

GAO, JH .

TETRAHEDRON LETTERS, 1994, 35 (18) :2819-2822

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