Practical syntheses of neopentyl alcohol and sec-butyl ethyl ether using Marukasol as a solvent

Article abstract of DOI:10.1021/op058003p

By using Marukasol, neopentyl alcohol and sec-butyl ethyl ether have been obtained in good yields with easy operations. Thus, neopentyl alcohol was obtained from tert-butylmagnesium chloride and paraformaldehyde in 76% isolated yield with >99% purity using Marukasol as an effective extraction solvent On the other hand, sec-butyl ethyl ether was obtained from sodium sec-butoxide with ethyl iodide in Marukasol in 67% yield with >99% purity.

Full text of DOI:10.1021/op058003p

Organic Process Research & Development 2005, 9, 825−826
Technical Notes
Practical Syntheses of Neopentyl Alcohol and sec-Butyl Ethyl Ether Using
Marukasol as a Solvent
Yoshifumi Yuasa* and Yasushi Kato
Takasago International Corporation, 1-5-1 Nishiyawata, Hiratsuka, Kanagawa, 254-0073, Japan
Abstract:
By using Marukasol, neopentyl alcohol and sec-butyl ethyl ether
have been obtained in good yields with easy operations. Thus,
neopentyl alcohol was obtained from tert-butylmagnesium
Figure 1. Structure of main component of Marukasol.
chloride and paraformaldehyde in 76% isolated yield with
>99% purity using Marukasol as an effective extraction solvent.
On the other hand, sec-butyl ethyl ether was obtained from
sodium sec-butoxide with ethyl iodide in Marukasol in 67%
yield with >99% purity.
Figure 2. Structures of Neopentyl alcohol 1 and sec-butyl ethyl
ether 2.
Introduction
Marukasol (trade name), produced by Maruzen Petro-
or tert-butyl acetic chloride using lithium aluminum hy-
chemical Co., Ltd., contains 2,2,4,6,6-pentamethylpen-
dride.5,6
tane (iso-dodecane) as the main component (Figure 1) and
In these methods, the use of formaldehyde and tert-
has been employed as a useful solvent in many fields
butylmagnesium chloride is considered suitable for economic
[see homepage of Maruzen Peterochemical Co., Ltd.;
reasons, but the purity and yield of 1 obtained are not
www.chemiway.co.jp/]. We have been studying the practical
satisfactory for large-scale production.
use of Marukasol and now report the efficient syntheses of
sec-Butyl ethyl ether (2) is useful as a flavoring material
for dentrifices and mouthwashes and can be synthesized by
neopentyl alcohol and sec-butyl ethyl ether, both of which
are not sold as reagent grade, using Marukasol as an
the Williamson method.7-9 This classical method is used
extraction or reaction solvent.
more widely in ether synthesis at present; however, an effi-
cient and practical synthesis of 2 has not been yet reported.
We have investigated a more practical synthesis of 1 using
formaldehyde and tert-butylmagnesium chloride with Maruka-
sol as an effective extraction solvent and of 2 using sodium
sec-butoxide with ethyl iodide with Marukasol as the reaction
solvent.
Neopentyl alcohol, 2,2-dimethyl-1-propanol (1), is known
to be a useful raw material (Figure 2).1 Many syntheses of
1 have been previously reported as follows; however, a
practical synthesis of 1 has not been reported.
(i) Conant et al. have reported a method using formal-
dehyde and tert-butylmagnesium chloride in 42-50% yield.2
(ii) Whitemore et al. have reported the synthesis of 1 from
tert-butylmagnesium chloride and tert-butyl acetyl chloride
Results and Discussion
in 71% yield.3
Initially, we attempted the synthesis of 1 from formal-
dehyde and tert-butylmagnesium chloride in diethyl ether
according to the above-described literature.2 The result was
not practically acceptable with regard to the isolated yield
of 1 which included residual water. Also, the use of
formaldehyde and diethyl ether should be avoided for safety
(iii) Adkins et al. have reported the synthesis of 1 from
the hydrogenation of tert-butyl acetic acid ethyl ester over
copper chromate at 250 °C in 88% yield.4
(iv) Nystrom et al. have reported the synthesis of 1 from
the reduction of tert-butyl acetic acid, ethyl tert-butyl acetate,
and environmental reasons. We tried using paraformaldehyde
instead of formaldehyde, and tert-butyl methyl ether and
* To whom correspondence should be addressed. Telephone: 81-(0)463-21-
7516. Fax: 81-(0)463-21-7413. E-mail: yoshifumi_yuasa@takasago.com.
(1) Faith, W. L. Industrial Chemicals, 2nd ed.; Wiley & Sons: New York,
1957; pp 107-114.
(2) Conant, J. B.; Webb, C. N.; Mendum, W. C. J. Am. Chem. Soc. 1929, 51,
1246.
(3) Greenwood, F. L.; Whitmore, F. C.; Crooks, H. M. J. Am. Chem. Soc.
1938, 60, 2028.
(4) Adkins, H.; Folkers, K. J. Am. Chem. Soc. 1931, 53, 1091.
(5) Nystrom, R. F.; Brown, W. G. J. Am. Chem. Soc. 1947, 69, 1198.
(6) Salom, S.; Newman, M. S. J. Am. Chem. Soc. 1956, 78, 5416.
(7) Williamson, W. J. Chem. Soc. 1852, 4, 106, 229.
(8) Vogel, A. I. J. Chem. Soc. 1948, 616.
(9) Patai, S. The Chemistry of the Ether Linkage; Wiley & Sons: New York,
1967; pp 446-448.
10.1021/op058003p CCC: $30.25 © 2005 American Chemical Society
Published on Web 09/08/2005
Vol. 9, No. 6, 2005 / Organic Process Research & Development
•
825

Table 1. Effect of extraction solvent upon the yield of 1a
using a Shimadzu GC-17A with an FID detector (Column
1: Neutrabond-1 produced by GL Sciences, Inc., Japan; df
) 0.25 mm ID × 30 m; carrier gas, N2, 0.1 Mpa; oven
temperature, 60-230 °C programmed at 5 °C/min; injection
temperature, 230 °C; detector temperature, 250 °C. 1, tr: 3.84
min. Marukasol, tr: 11.08-12.07 min. Column 2: TC-1, by
GL Sciences, Inc., Japan; df ) 0.25 mm ID × 30 m; carrier
gas, N2, 0.1 Mpa; oven temperature, 40 °C, isothermal 5 min
and then 40-230 °C programmed at 5 °C/min; injection
temperature, 230 °C; detector temperature, 250 °C. 2-Bu-
tanol, tr: 3.40 min. Ethyl iodide, tr: 3.54 min. 2, tr: 4.45
min. Marukasol, tr: 17.71-19.90 min).
Scale-Up Procedure for Neopentyl Alcohol (1). In a
10-L glass vessel, magnesium (252.8 g, 10.4 mol) and THF
(5.55 L) were added, and then tert-butyl chloride (1110.8 g,
12 mol) was added dropwise for 6 h at 35-40 °C. The
mixture was allowed to stand overnight. 95% Paraformal-
dehyde (597.4 g, 9.45 mol) was added at 25 °C and stirred
for 7 h at 45 °C. To the reaction mixture, Marukazol (5.55
L) was added, and 70% weight of THF was removed at
55-70 °C under reduced pressure (250 Torr). 20%
H2SO4 solution (10 L) was added to the residue and stirred
at 20-30 °C for 1 h. The organic layer was separated and
washed with water (5.5 L), 5% Na2CO3 solution (1.5 L),
and twice with 10% NaCl solution (2 L). The organic
solution (6.25 Kg) was distilled at 100-145 °C under
reduced pressure (240-260 Torr) to give neopentyl alcohol
(1) (623.7 g, 75% vs paraformaldehyde). The distilled
product was crystallized as clear white crystals. The purity
was 99.5% by GC.
isolated yield
of 1 (%)
solvent
1
2
3
n-hexane
p-cymene
Marukasol
60
65
75
a t-BuCl (1.3 equiv), Mg (1.1 equiv), and (CH2O)n (1.0 equiv) in THF were
used.
diisopropyl ether instead of diethyl ether were investigated
as reaction replacement solvents, but the reaction did not
proceed. However, the reaction proceeded when using THF.
Next, the amounts of tert-butyl chloride and magnesium for
paraformaldehyde in THF were investigated. The use of 1.3
mol equiv of tert-butyl chloride and 1.1 mol equiv of
magnesium for paraformaldehyde at 45 °C gave the best
results. Neopentyl alcohol, which was obtained by removal
of THF followed by distillation of the reactions, did not have
high purity and included water. An appropriate extraction
solvent is needed after the removal of THF. We tried using
n-hexane, Marukasol, and p-cymeme as extraction solvents,
which have either a low or a high boiling point, because it
was considered that the purification of 1 could easily be
performed by distillation. The results are shown in Table 1.
The result using Marukasol which has a high boiling point
and an effective solvent effect was preferred.
Second, we attempted the synthesis of 2 from sodium sec-
butoxide with ethyl iodide using Marukasol. Metalic sodium
and 3.3 mol equiv of sec-butanol were heated at 100 °C for
5 h to give sodium sec-butoxide. Excess sec-butanol was
removed, and Marukazol was then added. Ethyl iodide was
added dropwise at 85 °C for 1 h and allowed to react at
85-100 °C for 7 h. Ethyl iodide was found to be consumed
completely by GC. After the workup, a high purity of 2 was
obtained in 67% yield by distillation. When not using a
solvent such as Marukazol, it is difficult to purify 2 from
sec-butanol and ethyl iodide by distillation.
Bp 83-84 °C/245 Torr (lit.2 112-114 °C, lit.3 106-112
°C/737 mm). Mp 53 °C (lit.2 47-49 °C, lit.3 50 °C). The
NMR, IR, and EI-MS data are identical with the ones from
the literature.
Scale-Up Procedure for sec-Butyl Ethyl Ether (2). In
a 3-L glass vessel, sec-butanol (532 g, 7.18 mol) was charged
and heated at 55 °C. Metalic sodium (50 g, 2.175 mol) was
introduced over 35 min at the same temperature. The mixture
was stirred at 100 °C for 5 h. The reaction mixture was
cooled to 55 °C, and 60% weight of sec-butanol was removed
at 55-75 °C under reduced pressure (100 Torr). Marukazol
(1.1 L) was added to the residue, and ethyl iodide (305.3 g,
1.957 mol) was then added dropwise at 85 °C for 1 h. The
reaction mixture was stirred at 85-100 °C for 9 h. Ethyl
iodide was found to be consumed completely by GC. The
reaction mixture was cooled to 10 °C, and ice water (300
mL) was added. The organic layer was separated and washed
with ice water (500 mL × 4). The organic solution was dried
with anhydrous MgSO4 and distilled by column distillation
with a helipak No. 3 to give sec-butyl ethyl ether (2) (147.6
g, 67% vs metalic sodium). The purity was 99.4% by GC.
Bp 79-80 °C (lit.10 81°C). The NMR, IR, and EI-MS
data are identical with the ones from the literature.
In a large-scale production, we have already produced
700 g of 1 with 99.5% purity in 75% yield from 1 kg of
paraformaldhyde and 150 g of 2 with 99% purity in 67%
yield from 50 g of metalic sodium using the above-described
methods without difficulty.
Experimental Section
Marukasol was purchased from Maruzen Petrochemical
Co., Ltd. All reagents and other solvents were obtained from
commercial sources and used without further purification.
For determining the melting points, a Yanagimoto mi-
cromelting apparatus was used, and the values are uncor-
rected values. Boiling points: uncorrected. NMR: Bruker
DRX-500. 1H and 13C NMR were measured at 500 and 125
MHz, respectively. The NMR spectra were recorded in
CDCl3 with TMS as the internal standard. The chemical shifts
were given in δ (ppm). IR: Nicolet Avatar 360 FT-IR. MS:
Hitachi M-80A mass spectrometer at 70 eV. GLC was done
Received for review April 14, 2005.
OP058003P
(10) Lide, D. R.; Milne, G. W. A. Handbook of Data on Organic Compounds,
3rd ed.; CRC Press: 1993; p 1825.
826
•
Vol. 9, No. 6, 2005 / Organic Process Research & Development