One-pot synthesis from 1,4-cyclohexadiene of (±)-1,4/2,5-cyclohexanetetrol, a naturally occurring cyclitol derivative

Article abstract of DOI:10.1016/S0008-6215(98)00073-1

SeO₂-catalyzed direct hydroxylation of 1,4-cyclohexadiene with two molar equivalents of 30% H₂O₂ afforded (±)-1,4/2,5-cyclohexanetetrol, a naturally occurring cyclitol derivative, as the sole product in a good yield (88%).

Full text of DOI:10.1016/S0008-6215(98)00073-1

Carbohydrate Research 308 (1998) 435±437
Note
One-pot synthesis from 1,4-cyclohexadiene of
(‹)-1,4/2,5-cyclohexanetetrol, a naturally
occurring cyclitol derivative
Ahmet Maras, Mesut Erden, Hasan Secen*, Yasar Sutbeyaz*
,
Department of Chemistry, Faculty of Arts and Sciences, Ataturk University, 25240 Erzurum, Turkey
Received 1 August 1997; accepted 20 December 1997
Abstract
SeO2-catalyzed direct hydroxylation of 1,4-cyclohexadiene with two molar equivalents of 30%
H2O2 a€orded (‹)-1,4/2,5-cyclohexanetetrol, a naturally occurring cyclitol derivative, as the sole
product in a good yield (88%). # 1998 Elsevier Science Ltd. All rights reserved
Keywords: (‹)-1,4/2,5-Cyclohexanetetrol; 1,4-Cyclohexadiene; Selenium dioxide
For many years the cyclitols [1,2] have been
recognized as a small group of natural products,
but nowadays their status has changed as a result
of extensive chemical and biochemical investiga-
tions. In this context, cyclohexanetetrols, a class of
cyclitols, are worthy of attention. So far, only three
naturally occurring cyclohexanetetrol isomers have
been reported: Betitol [3], d-(+)-1,4/2,5-cyclohex-
anetetrol [4,5] (2a), and toxocarol [6]. Betitol was
reported to be present in very small amounts in
sugarbeet molasses. The proposed structure of
Subsequently, they isolated tetrol 2a from an alga
of the genus Porphyridium [5]. Toxocarol isolated
from a plant source (Toxocarpus himalensis Falc.
Ex Hook. f.) was reported to be 1,4/2,3-cyclohex-
anetetrol [6]. One of the stereospeci®c syntheses for
toxocarol started from 1,3-cyclohexadiene, and
was reported in our previous study [7].
The ®rst synthesis of tetrol 2a presumably was
performed by Zelinsky and Titowa [8]. They con-
verted 1,4-cyclohexadiene (1) into a dioxide (mp
ꢀ
110 C) which was hydrolyzed to a tetrol (mono-
ꢀ
ꢀ
betitol (mp 224 C) is mainly based on elemental
hydrate, mp 195 C). This product probably cor-
analyses, a negative response to Fehling's reagent,
and its conversion to quinone by oxidation with
KMnO4 and H2SO4. However, the occurrence of
betitol has never been con®rmed and the structure
remains uncertain [2]. Craigie and collaborators [4]
isolated tetrol 2a from the marine alga Monochrysis
lutheri and described most of the physical data.
responds to tetrol 2a. Tetrol 2a was also prepared
by hydrogenolytic reduction of inositol dibromo-
hydrins by McCasland and Horswill [9]. McCas-
land et al. [10,11] also synthesized tetrol 2a beside a
small proportion of meso-1,5/2,4-cyclohexanetetrol
(3) by trans-hydroxylation of 1,4-cyclohexadiene
(1), or of trans-cyclohexene-4,5-diol dibenzoate
using the Prevost method. Craig et al. [12] also
synthesized tetrol 2a as a sole product by acidic
* Corresponding authors.
0008-6215/98/$19.00 # 1998 Elsevier Science Ltd. All rights reserved
PII S0008-6215(98)00073-1

436
A. Maras et al./Carbohydrate Research 308 (1998) 435±437
hydrolysis of cis- and trans-1,4-cyclohexadiene
dioxide similar to Zelinsky's method. We now pre-
sent a new and more ecient method to give tetrol
2a by direct hydroxylation of 1,4-cyclohexadiene (1).
In our approach we focused on the hydroxyla-
tion of 1,4-cyclohexadiene (1) with H2O2 in the
presence of SeO2 (Scheme 1). By this method, the
formation of a trans-diol was directly accomplished
[13] presumably via a perselenious acid species.
Recently, we reported on the synthesis of proto-
quercitol and vibo-quercitol by hydroxylation of
cyclohex-5-ene-1,4/2-triol [14] without anchimeric
assistance using this method.
According to studies of Craig et al. [12], both cis-
and trans-1,4-cyclohexadiene dioxide give only
tetrol 2a. We assumed that the SeO2-catalyzed
hydoxylation method also proceeded by an in situ
epoxidation followed by acidic hydrolysis, gen-
erating tetrol 2a directly by this method.
Indeed, hydroxylation of 1,4-cyclohexadiene (1)
with two molar equivalents of 30% H2O2 in the
presence of SeO2 gave tetrol 2a in a good yield
(88%) as a sole product. Although compound 3 is
also a possibly expected product as a result of the
reaction, NMR analysis of the crude product did
not show any signal that belongs to meso-1,5/2,4-
cyclohexanetetrol (3). The structural assignment of
2a was easily made by comparison of the 1H NMR
[11] and physical data with those previously pub-
lished. Tetrol 2a was converted to its tetraacetate
2b for further structural proof; the NMR and
physical data of 2b were also in agreement with
published values.
In conclusion, even though the SeO2-catalyzed
hydroxylation method with H2O2 has very restric-
ted examples in the literature, in our present study,
a new and very versatile application has been
shown by synthesis of the racemic form of natural
tetrol 2a in only one step.
1. Experimental
(‹)-1,4/2,5-Cyclohexanetetrol
(2a).ÐTo
a
stirred solution of selenium dioxide (5.6 mg,
0.63 mmol) in t-BuOH (7.5 mL) was added 1,4-
cyclohexadiene (1) (2.00 g, 25 mmol). To the result-
ing mixture 30% H2O2 (5.60 g, 50 mmol) was added
dropwise over 20 min at room temperature. Addi-
tionally, the mixture was stirred for 24 h at room
temperature, then NaHSO3 (500 mg) was added to
reduce possibly unreacted H2O2. The solid pre-
cipitate was ®ltered, then washed with EtOH. The
®ltrates were combined and concentrated under
reduced pressure to give a syrup. Hot EtOH
(50 mL) was added to the syrup, and after ®ltration
EtOH was evaporated to give 1,4/2,5-cyclohex-
anetetrol (2a) (3.26 g, 88%). Compound 2a was
recrystalized from absolute EtOH to a€ord a col-
ꢀ
orless crystalline product (mp 194±196 C; lit. [4]
[(+)-isomer] mp 205±207 ꢀC ꢀ(with decomp.), lit. [5]
[(+)ꢀ-isomer] mp 202±204.5 C, lit. [9] mp 207.5±
ꢀ
208 C, lit. [10]ꢀmp 208 C, lit. [12] mp from 191±
193 to 196±197 C). 1H NMR (200 MHz, CD3OD):
ꢀ 3.73 (m, 4 H), 1.84 (m, 4 H); 13C NMR (50 MHz,
CD3OD): ꢀ 73.47, 37.53. 1H NMR (200 MHz,
D2O): ꢀ 3.71 (m, 4 H), 1.78 (m, 4 H); 13C NMR
(50 MHz, D2O): ꢀ 74.42, 38.30. IR (KBr): ꢁ 3285,
3004, 2953, 2927, 2493, 2417, 1497, 1370, 1217,
1
1063, 910 cm .
(‹)-1,4/2,5-Cyclohexanetetrol tetraacetate (2b).Ð
Tetrol 2a was acetylated with Ac2O-pyridine as
described in our published procedure for the synth-
esis of conduritol-E tetraacetate [15] to give 2b;
Yield: 86%; colorless syrup; mp 144±145 ꢀC, recrys-
tallized from CH2Cl2±hexane, lit. [10,11] mp 148 ꢀC.
1H NMR (200 MHz, CDCl3): ꢀ 5.03 (m, 4 H), 2.03
(m, 4 H; s, 12 H). 13C NMR (50 MHz, CDCl3): ꢀ
171.65, 71.09, 32.15, 22.90. IR (KBr): ꢁ 2978, 1753,
1
1446, 1395, 1248, 1191, 1038, 936, 910 cm .
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