ChemSusChem
10.1002/cssc.201802138
COMMUNICATION
o
are relatively stable compared with usual primary aliphatic
a 10 mL Schlenk tube under air, was stirred at 50 C for 24 h, monitored
by TLC and/or GC-MS, and purified by thin layer chromatography on
silica gel using ethyl acetate and petroleum ether (0~1/10) as the eluent.
N
cations, the S 1 mechanism through formation of benzylic
cations can still not be excluded completely for the primary
benzylic halides. With the sterically most bulky tertiary halides,
2
a was obtained in 83% isolated yield.
S
N
2 mechanism should be impossible, especially in the case of
adamantyl bromide (Table 2, entries 29-30) that cannot allow
backside attack of DMSO. Instead, S 1 mechanism should
Acknowledgements
N
occur with formation of the stable tertiary carbon cations. Except
the adamantyl bromide to which DMSO can only attack from
outside and give configuration-reserved intermediates and
products, usual tertiary halides should afford racemized
intermediates and products via attack of DMSO from both side
We thank National Natural Science Foundation of China
(21672163) and Natural Science Foundation of Zhejiang
Province for Distinguished Young Scholars (LR14B020002) for
financial support. We also thank Prof. Zhan Lu (Zhejiang
University) and Dr. Jianhui Chen (Wenzhou University) for
helpful discussions.
N N
of the tertiary cations. Although both S 1 and S 2 mechanisms
may work with secondary halides according to the text book
knowledge, it is still unknown which one would dominate the
reaction. Therefore, an optically-enriched (S)-1-phenylethyl
Keywords: alcohols
• dimethyl sulfoxide • hydrolysis •
[
19,22]
bromide (1m)
was employed to react with DMSO. As shown
organohalides • oxygen transfer
in eq. 4, when (S)-1m of 50% ee was treated with DMSO under
the standard conditions, only a very low ee (2%) of the target
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S
N
1 mechanism is the dominant process in the reaction of
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In conclusion, we developed a DMSO-accelerated aqueous
hydrolysis of organohalides by adding DMSO as a co-solvent,
providing a neutral, more efficient, milder and more economic
new process for preparation of alcohols from organohalides.
[3]
18
18
2
Mechanistic studies using O-DMSO and O-H O revealed that
the accelerating effect of DMSO comes from a DMSO-triggered
complete oxygen transfer process through O-attack of DMSO at
the electrophilic RX and generation of alkoxysulfonium salts
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+
-
ROS Me
2
·X with C-O bonding, followed by O-S bond
+
-
disassociated hydrolysis of ROS Me
2
·X with water. This new
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merely as a dipolar solvent to enhance the nucleophilicity of
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[5c,11,12c]
water in the hydrolysis reaction.
This work may thus be a
good advance in the field by clarifying the true role of DMSO in
the reaction mechanism. Since a wide range of organohalides
can be used as the substrate and due to the easy recovery of
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2
DMSO from H O/DMSO mixture by usual vacuum rectification,
this method may be of potential practical applications in
industrial synthesis. Further applications of the DMSO-triggered
oxygen transfer reaction in other types of organic reactions are
underway in this group.
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Experimental Section
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Typical procedure for DMSO-facilitated neutral hydrolysis of
organohalides (method A): The mixture of benzyl bromide (0.12 mL, 1
mmol), extra dry DMSO (0.33 mL), and H O (0.17 mL), sealed directly in
2
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