The reactivity of potassium carbanions with epoxides

Article abstract of DOI:10.1080/00397911.2012.702291

Cyclohexene oxide reacted with n-butylpotassium unexpectedly to produce 2-butylcyclohexanone in a 10% isolated yield of its semicarbazone derivative. Based on previous literature, a three-part mechanism is proposed that implies that a yield greater than 33% is not possible. Copyright

Full text of DOI:10.1080/00397911.2012.702291

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The Reactivity of Potassium Carbanions
with Epoxides
Christina Dorado a & James M. Salvador a
a Department of Chemistry , University of Texas at El Paso , El Paso ,
Texas , USA
Published online: 03 Jun 2013.
To cite this article: Christina Dorado & James M. Salvador (2013) The Reactivity of
Potassium Carbanions with Epoxides, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 43:17, 2314-2318, DOI:
10.1080/00397911.2012.702291
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Synthetic Communications1, 43: 2314–2318, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2012.702291
THE REACTIVITY OF POTASSIUM CARBANIONS
WITH EPOXIDES
Christina Dorado and James M. Salvador
Department of Chemistry, University of Texas at El Paso, El Paso,
Texas, USA
GRAPHICAL ABSTRACT
Abstract Cyclohexene oxide reacted with n-butylpotassium unexpectedly to produce
2-butylcyclohexanone in a 10% isolated yield of its semicarbazone derivative. Based on
previous literature, a three-part mechanism is proposed that implies that a yield greater
than 33% is not possible.
Supplemental materials are available for this article. Go to the publisher’s online edition
of Synthetic Communications1 to view the free supplemental file.
Keywords 2-Butylcyclohexanone; carbanions; a-cumylpotassium; epoxides; organometallic
reagents; semicarbazone
INTRODUCTION
The literature describes the combination of a potassium alkoxide and n-butyl-
lithium as a ‘‘superbase’’ or LiCKOR reagent with metalating capabilities.[1] Alkyl
potassiums[2–4] prepared in a similar manner[1] have also been reacted with ferro-
cene,[2] a-olefins,[5] toluene, cross-linked polystyrene derivatives,[3] and saturated
ethers to produce metalated products.[2–5] In particular, the reaction of n-butylpotas-
sium with cyclohexene oxide was expected to produce cyclohex-2-en-1-ol just as
n-butyllithium does when reacted with cyclohexene oxide,[6] but the reaction of
a-cumylpotassium with cyclohexene oxide to produce trans-cumylcyclohexanol by
nucleophilic substitution[7] (Scheme 1) indicated that organopotassium species are
not simply metalating agents but can be effective nucelophiles.
Received May 14, 2012.
Address correspondence to Christina Dorado, Department of Chemistry, University of Texas at El
Paso, 500 W. University Ave., El Paso, TX 79968, USA. E-mail: calvarado4@miners.utep.edu
2314

REACTIVITY OF POTASSIUM CARBANIONS WITH EPOXIDES
2315
Scheme 1. Synthesis of racemic trans-cumylcyclohexanol.
DISCUSSION
The reaction of n-butylpotassium with cyclohexene oxide was studied. If
n-butylpotassium were to react with cyclohexene oxide by the same substitution
mechanism as a-cumylpotassium, the expected product would be trans-2-
butylcyclohexan-1-ol (Scheme 2). The reaction of 1.2 equivalents of potassium-
tert-amylate and 1 equivalent of n-butyllithium and cyclohexene oxide afforded
not only the expected elimination product (cyclohex-2-en-1-ol) but also new signals
corresponding to 2-butylcyclohexanone by 13C NMR that agreed with the literature
values,[8] but there was no evidence of the predicted substitution product. To verify
the identity and quantify this unique product, 2-butylcyclohexanone was isolated in
a 2% yield by radial chromatography and mass analyzed. Noting the volatility of this
spearmint-scented ketone, semi-carbazide was added to the crude reaction mixture to
give a 10% yield of the semicarbazone with a melting point for the recrystallized pro-
duct in ethanol of 134 ꢀC (lit. 138.5–150 ꢀC[9–12]). 13C NMR data for the semicarba-
zone could not be found in the literature, but the 13C NMR of the synthesized
semicarbazone, included in the Supporting Information (available online), agreed
with a simulated spectrum calculated using 13C NMR Predictor Software from
ACD Labs. A review of the literature gave insight into the mechanism for the con-
version of cyclohexene oxide to 2-butylcyclohexanone. First, the work done by
Hodgson et al. describes that in the presence of a strong base epoxides can rearrange
to enolates through a carbene intermediate[13] (Scheme 3). Second, work conducted
by Oku et al. describes that ketones can be produced when carbenes react with sec-
ondary alkoxides by hydride abstraction[14] (Scheme 4). The literature led us to pos-
tulate the following three-step mechanism: First, 2-butylcyclohexanone is produced
by opening the epoxide ring of cyclohexene oxide by an SN2 substitution with
Scheme 2. Predicted product of reaction of n-butylpotassium and cyclohexene oxide, racemic trans-
2-butylcyclohexanol.

2316
C. DORADO AND J. M. SALVADOR
Scheme 3. Rearrangement of an epoxide in the presence of a strong base.
Scheme 4. Conversion of secondary alkoxide to ketone via hydride abstraction.
n-butylpotassium to make the alkoxide of trans-2-butylcyclohexan-1-ol (1) as
predicted. Next, a second equivalent of n-butylpotassium reacts with cyclohexene
oxide to produce a carbene alkoxide (2) as postulated by Hodgson. Finally, the
carbene alkoxide (2) oxidizes the alkoxide of trans-2-butylcyclohexan-1-ol (1) to
2-butylcyclohexanone (3) as observed in Oku’s chemistry, which is then converted
to the corresponding enolate (4) by a third equivalent of n-butylpotassium
(Scheme 5). In addition to the volatility of 2-butylcyclohexanone, the incomplete iso-
lation of its semicarbazone after recrystallization, and the competing elimination of
cyclohexene oxide to cyclohex-2-en-1-ol, the proposed mechanism also explains why
a yield greater than 33% is not possible. We continue to study the range of the
Scheme 5. Proposed mechanism for the production of 2-butylcyclohexanone.

REACTIVITY OF POTASSIUM CARBANIONS WITH EPOXIDES
2317
reactivity of organopotassium species with epoxides, including how to isolate the
proposed initial ring-opening products.
EXPERIMENTAL
Synthesis of 2-Butylcyclohexanone
To a clean and dry 100-mL, round-bottom flask with magnetic stir bar and rub-
ber septum were added 40 mL of 1.2 M potassium tert-amylate (48 mmol) and 16 mL
of 2.5 M n-butyllithium (40 mmol) dropwise via syringe under nitrogen gas. After
15 min, the reaction formed a white precipitate and 3.74 g of cyclohexene oxide
(38.1 mmol) was added dropwise. The reaction was stirred a further 2 h, and then
30 mL of deionized water were added and the yellow organic layer was washed with
more water (2 ꢁ 30 mL). The combined aqueous layers were extracted with dichloro-
methane (3 ꢁ 30 mL), and the combined organic layers were dried over potassium car-
bonate and decanted into a round-bottom flask. The solvent was removed via vacuum
distillation on a rotary evaporator, and the remaining light yellow oil was distilled
bulb to bulb utilizing a Kugelrohr apparatus to give 1.18 g of crude product. Radial
chromatography was performed on the distillate to identify and quantify the percent-
age yield of 2-butyl cyclohexanone as follows: A 5% ethyl acetate=hexane solution
was prepared and utilized to moisten the 0.25 in rotating silica plate. To the moistened
silica plate was added 0.28 g of crude sample. An ultraviolet light was utilized to
observe and collect the first band as it eluted from the plate. The solvent was evapo-
1
rated utilizing aspirator pressure giving 0.03 g (2%) of isolated product. The H
NMR, 13C NMR, and mass spectrum analysis coincide with the literature data.[8]
Synthesis of 2-Butylcyclohexanone Semicarbazone
To a clean and dry 100-mL round-bottom flask with magnetic stir bar and rub-
ber septum were added 10 mL of 1.2 M potassium tert-amylate (12 mmol) and 0.99 g
of cyclohexene oxide (10.1 mmol) via syringe under nitrogen gas. To the flask was
added 4 mL of 2.5 M n-butyllithium (10 mmol) dropwise. The reaction was stirred
for a further 1 h, and then 30 mL of deionized water was added and the yellow
organic layer was washed with more water (2 ꢁ 30 mL). The combined aqueous
layers were extracted with hexane (3 ꢁ 30 mL), and the combined organic layers were
poured into a 250-mL, round-bottom flask. To the flask were added 1.57 g of sodium
acetate and 0.98 g semi-carbazide, and it was shaken vigorously until a white solid
formed. The remaining solvent was evaporated via vacuum distillation on a rotary
evaporator and the remaining light yellow oil was allowed to cool until crystals
formed. The remaining crystals were then washed with cold ethanol to give 0.19 g
of semicarbazone or 0.154 g of 2-butylcyclohexanone (10%). The semicarbazone
was recrystallized using ethanol to give fine white crystals: mp 134 ꢀC (lit. mp.
138.5–139.5 ꢀC) 13C NMR (CDCl3) d ¼ 14.105, 22.867, 23.754, 25.144, 26.306,
29.458, 30.700, 33.018, 43.996, 155.652, 157.915.
SUPPORTING INFORMATION
1H and 13C NMR spectra can be found online in the Supporting Information
for this article.

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C. DORADO AND J. M. SALVADOR
ACKNOWLEDGMENTS
We gratefully acknowledge the support of the Department of Chemistry and
Graduate School of the University of Texas at El Paso and the funding provided
by the Louis Stokes Alliance for Minority Participation Bridge to the Doctorate
Fellowship (HRD-0832951). We also acknowledge the generous donation of potass-
ium tert-amylate by BASF.
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