( ewcommandvecs<1>overset scriptstyle ightharpoonup mathbf#1) ( ewcommandvecd<1>overset-!-! ightharpoonupvphantomasmash#1 )( ewcommandidmathrmid) ( ewcommandSpanmathrmspan) ( ewcommandkernelmathrmnull,) ( ewcommand angemathrmrange,) ( ewcommandRealPartmathrmRe) ( ewcommandImaginaryPartmathrmIm) ( ewcommandArgumentmathrmArg) ( ewcommand orm<1>\) ( ewcommandinner<2>langle #1, #2 angle) ( ewcommandSpanmathrmspan) ( ewcommandidmathrmid) ( ewcommandSpanmathrmspan) ( ewcommandkernelmathrmnull,) ( ewcommand angemathrmrange,) ( ewcommandRealPartmathrmRe) ( ewcommandImaginaryPartmathrmIm) ( ewcommandArgumentmathrmArg) ( ewcommand orm<1>\) ( ewcommandinner<2>langle #1, #2 angle) ( ewcommandSpanmathrmspan)

The Birch Reduction

An early method of preparing phenol (the Dow process) involved the reaction of chlorobenzene with a concentrated sodium hydroxide solution at temperatures above 350 ºC. The chief products are phenol and diphenyl ether (see below). This apparent nucleophilic substitution reaction is surprising, since aryl halides are generally incapable of reacting by either an SN1 or SN2 pathway.

Bạn đang xem:

C6H5–Cl + NaOH solution 350 ºC
*
C6H5–OH + C6H5–O–C6H5 + NaCl

The presence of electron-withdrawing groups (such as nitro) ortho and para to lớn the chlorine substantially enhance the rate of substitution, as shown in the set of equations presented below.

*

To explain this, a third mechanism for nucleophilic substitution has been proposed. This two-step mechanism is characterized by initial addition of the nucleophile (hydroxide ion or water) to the aromatic ring, followed by loss of a halide anion from the negatively charged intermediate as illustrated below. The sites over which the negative charge is delocalized are colored blue, & the ability of nitro, and other electron withdrawing, groups khổng lồ stabilize adjacent negative charge accounts for their rate enhancing influence at the ortho & para locations.

*

Three additional examples of aryl halide nucleophilic substitution are presented below. Only the 2- & 4-chloropyridine isomers undergo rapid substitution, the 3-chloro isomer is relatively unreactive. Nitrogen nucleophiles will also react, as evidenced by the use of Sanger"s reagent for the derivatization of amino acids. The resulting N-2,4-dinitrophenyl derivatives are bright yellow crystalline compounds that facilitated analysis of peptides và proteins, a subject for which Frederick Sanger received one of his two Nobel Prizes in 91neg.comistry.

Xem thêm: Xem Sao Tử Vi 2021 Của 12 Con Giáp & Xem Bói Tài Lộc, Tình Duyên

Additional Examples

-->