Organic Process Research & Development 2003, 7, 185
Technical Notes
Recyclable Lucas Reagent in Converting Aliphatic Alcohols to Chlorides1
Pushpananda A. Senaratne,* Felix M. Orihuela, Arcelio J. Malcolm, and Keith G. Anderson
Albemarle Technical Center, Albemarle Corporation, P.O. Box 14799, Baton Rouge, Louisiana 70898, U.S.A.
Scheme 1
Abstract:
An industrially viable and environmentally friendly process is
developed for the synthesis of menthyl chloride from the
corresponding alcohol. Menthyl chloride was made in high yield
by the reaction of menthol with the Lucas reagent. This
chlorinating reagent was then recycled in the subsequent runs
by simply replenishing the HCl, making the process simple and
commercially viable. This improved procedure minimized the
costly disposal of used Zn salts.
this methodology to synthesize multikilogram quantities of
menthyl chloride from menthol by minimizing the disposal
of used zinc salts. Thus, the Lucas reagent was made by
bubbling HCl gas into an aqueous solution of ZnCl2 (70%)
to obtain a 1:1 solution of ZnCl2:HCl. Menthol was then
introduced into this solution and stirred at ambient temper-
ature to obtain menthyl chloride in 95% yield. The reaction
was fast and was complete within 0.5 h, making the process
a very cost-effective plant operation.
Smith and Wright have shown from their work that the
reaction of ZnCl2/HCl on (-)menthol gives mainly one
enantiomer, that is, menthyl chloride. Our results concur with
the above observation.7 The other enantiomer, neomenthyl
chloride, undergoes rapid E2 elimination of HCl to give an
isomeric mixture of menthenes. Unlike menthyl chloride, the
stable chair conformation of the neomenthyl choride has two
axial hydrogen atoms trans to the axial chlorine, thus
promoting the E2 elimination of HCl.8 The small amount of
olefinic byproduct detected by the NMR analysis of the crude
product resulted from the decomposition of neomenthyl or
menthyl chloride or both.
After completion of the reaction, the organic layer was
separated from the aqueous phase, which contained the active
reagent. The aqueous phase was then treated with more HCl
to maintain the chloride concentration, and the reaction was
continued with the next batch of menthol. The reagent was
successfully recycled several times without having to dispose
of the Zn salts. The activity of the reagent was not diminished
for at least four reaction cycles, and the reaction was con-
tinued without further addition of ZnCl2. The waste disposal
of the process was greatly diminished, making this an envi-
Methodology for the generation of alkyl halides from the
corresponding alcohols has been extensively examined.2
Several reagents have been used in this reaction, and the
most common are halogen acids and inorganic acid halides.
Although halogen acids are more economical to use on an
industrial scale, HCl is not the most preferred reagent in
converting secondary alcohols to secondary chlorides. During
their pioneering work, Norris and Taylor3 successfully
converted alcohols into their corresponding bromides and
iodides by treating with the respective halo acids. Since HCl
gave poor results in this reaction, its reactivity was improved
by adding ZnCl2.4 Lucas improved this reaction further and
extended its scope to an analytical method to distinguish
between primary, secondary, and tertiary alcohols.5 The mild
reaction conditions and high yields make the Lucas reaction
an attractive methodology to utilize in the industrial-scale
preparation of alkyl chlorides from aliphatic alcohols.
However, the wide use of the Lucas reagent in industrial
settings is limited due to the cost of ZnCl2 and the waste
disposal of used Zn salts following the reaction.
As a part of an ongoing research program, we needed
large quantities of menthyl chloride. During our initial lab
trials, anhydrous ZnCl2 and concentrated HCl at 35 °C
conveniently converted L(-)menthol (1) to L(-)menthyl
chloride (2) in excellent yields (Scheme 1).6 We modified
* To whom correspondence should be addressed. E-mail: Telephone: 225-
(1) Senaratne, K. P. A.; Orihuela, F. M.; Malcolm, A. J. U.S. Patent 6,020,-
284, 2000.
(2) Pizey, J. S. Synthetic Reagents; Wiley: New York, 1974; Vol. 1, pp 321-
357. Brown, G. B. In The Chemistry of the Hydroxyl Group; Patai, S.,
Ed.; Interscience: New York, 1971; Part 1, pp 595-622. Guyer, A.; Bieler,
A.; Hardmeier, E. HelV. Chim. Acta, 1937, 20, 1462. Vogel, A. J. Chem.
Soc. 1943, 636.Larock, R. C. ComprehensiVe Organic Reactions; VCH:
New York, 1989; pp 353-360.
(7) The resulting chloride is converted to the corresponding diphenyl phosphine
by reacting with diphenylphosphide anion. The chiral integrity of the product
is confirmed by 31P NMR. A single peak at -14 ppm, which corresponds
to neomenthyldiphenyl phosphine was observed (the reaction proceeds via
inversion at the chiral center). Thus, menthyl chloride is the major product
formed from the halogenation reaction.
(3) Norris, J. F.; Taylor, H. B. J. Am. Chem. Soc. 1907, 38, 627.
(4) Norris, J. F.; Taylor, H. B. J. Am. Chem. Soc. 1924, 46, 753.
(5) Lucas, H. J. J. Am. Chem. Soc. 1930, 52, 802.
(8) March, J. AdVanced Organic Chemistry; Interscience: New York, 1985;
(6) Smith, J. G.; Wright, G. F. J. Org. Chem. 1952, 17, 1116.
pp 876-877.
10.1021/op0200266 CCC: $25.00 © 2003 American Chemical Society
Published on Web 12/31/2002
Vol. 7, No. 2, 2003 / Organic Process Research & Development
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