A new synthesis of 5,8-dimethyl-2-tetralone - A potential intermediate for the synthesis of ring-A aromatic sesquiterpenes. Novel transformation during acetoxylation of 5,8-dimethyldihydronapthalene

Article abstract of DOI:10.1081/SCC-120038516

An efficient synthesis of 5,8-dimethyl-2-tetralone 4 starting from 5,8-dimethyl-1-tetralone 2 is described. It was converted into the unsaturated derivative 3, which on epoxidation followed by acid hydrolysis yielded tetralone 4. Acetoxylation of 3 with manganese(III) acetate and potassium bromide afforded dimethylnaphthalene 8 and derivative 9.

Full text of DOI:10.1081/SCC-120038516

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A New Synthesis of 5,8‐Dimethyl‐2‐tetralone—A
Potential Intermediate for the Synthesis
of Ring‐A Aromatic Sesquiterpenes. Novel
Transformation During Acetoxylation of
5,8‐Dimethyldihydronapthalene
Ajoy K. Banerjee a , William Vera a & Manuel S. Laya a
a Centro de Química, IVIC, Apartado 21827, Caracas, 1020‐A, Venezuela
Version of record first published: 17 Aug 2006.
To cite this article: Ajoy K. Banerjee, William Vera & Manuel S. Laya (2004): A New Synthesis of
5,8‐Dimethyl‐2‐tetralone—A Potential Intermediate for the Synthesis of Ring‐A Aromatic Sesquiterpenes. Novel
Transformation During Acetoxylation of 5,8‐Dimethyldihydronapthalene, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 34:12, 2301-2308
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 12, pp. 2301–2308, 2004
A New Synthesis of 5,8-Dimethyl-2-
tetralone—A Potential Intermediate
for the Synthesis of Ring-A Aromatic
Sesquiterpenes. Novel Transformation
During Acetoxylation of 5,8-
Dimethyldihydronapthalene†
*
Ajoy K. Banerjee, William Vera, and
Manuel S. Laya
´
Centro de Quımica, IVIC, Caracas, Venezuela
ABSTRACT
An efficient synthesis of 5,8-dimethyl-2-tetralone 4 starting from 5,8-
dimethyl-1-tetralone 2 is described. It was converted into the unsaturated
derivative 3, which on epoxidation followed by acid hydrolysis yielded
†Dedicated to the memory of Dr. Marcel Roche, founder and Director of our Institute
(IVIC).
*
´
Correspondence: Ajoy K. Banerjee, Centro de Quımica, IVIC, Apartado 21827,
Caracas 1020-A, Venezuela; Fax: þ58-212-5041350; E-mail: abanerje@ivic.ve.
2301
DOI: 10.1081/SCC-120038516
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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Banerjee, Vera, and Laya
tetralone 4. Acetoxylation of 3 with manganese(III) acetate and potassium
bromide afforded dimethylnaphthalene 8 and derivative 9.
Key Words: Manganese(III) acetate; Friedel–Crafts alkylation;
Occidol; Dimethyl tetralone.
INTRODUCTION
Recently a very lengthy synthetic route to tetralone 4 has been published.[1]
The transformations of compound 4 to eudesmane sesquiterpenes occidol 5
and emmotin-G 6 can easily be carried out by standard organic reactions.[2–4]
Therefore we have developed a practically convenient route to tetralone 4
whose details are described in the present communication (Sch. 1). The present
work has the merit of relative brevity.
RESULTS AND DISCUSSIONS
As starting material we have chosen the commercially available p-xylene,
which via Friedel–Crafts alkylation with 4-chlorobutyric acid yielded acid
Scheme 1. Reagents: (i) PPa; (ii) PTSA, 2,4 pentanediol, toluene; (iii) McPBA,
CH2Cl2; and (iv) H2SO4–H2O.

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Synthesis of 5,8-Dimethyl-2-tetralone
2303
1 (Sch. 1). On cyclization with polyphosphoric acid (100%, Aldrich) the
known[4] tetralone 2 was obtained in excellent yield, which was converted to
dihydronapthalene 3 by heating in toluene with 2,4-pentanediol and
p-toluenesulphonic acid.[5] Treatment of 3 with m-chloroperbenzoic acid
in dichloromethane for several hours at room temperature, followed by
hydrolysis of the intermediate epoxide with dilute sulphuric acid yielded
tetralone 4 in 46% yield, whose spectroscopic data were consistent with the
data reported.[1]
Originally we planned to obtain tetralone 4 by allylic oxidation of 3
followed by catalytic hydrogenation. This plan, however, failed because
allylic oxidation[6] of 3 with CrO3 2C5H5N or a mixture of CrO3–3,5-
.
dimethylpyrazole, afforded a mixture of products (by TLC), which on chroma-
tographic purification could not be separated and characterized.
As an alternative, compound 3 was treated with manganese(III) acetate and
potassium bromide expecting to yield[6,7] acetate 7, whose transformation to
tetralone 4 can easily be accomplished[6] in three steps (alkaline hydrolysis, cata-
lytic hydrogenation, and oxidation). The desired product 7, however, could not
be isolated. On chromatographic purification of the reaction mixture, two pro-
ducts (8 and 9) were obtained. On the basis of spectroscopic evidence, the major
product (60%), was identified as 1,4-dimethylnaphthalene 8 (Sch. 2).
The spectral data of the other product, isolated in 40% yield, allowed us
assign to it structure 9. Its IR spectrum exhibited an absorption of the ester
carbonyl at 1736 cm21. It had a molecular ion 216 (Mþ 2 HBr) and 174
1
(216 2 CH2CO) (100%). H NMR spectrum exhibited two broad singlets at
d 6.94 (1H) and d 6.91(1H), assignable to protons at C-7 and C-6, respectively.
The signal at d 6.12 (1H) showed a doublet (J ¼ 2.5 Hz) whereas the signal at
d 4.63 (1H) exhibited quartet (J ¼ 2.6 Hz). As expected the 1H NMR spectrum
depicted three signals at d 2.33 (3H, s), d 2.23 (3H, s), and d 2.12 (3H, s),
which corresponds to aromatic methyls and acetate, respectively. These
spectroscopic data excluded structure 7. The above mentioned 1H NMR
data show that acetate and bromine of 9 are at C-1 and C-2, respectively,
and indicate that both the acetate and the bromine occupy pseudo axial con-
figuration.[8] The molecular model of olefin 3 (Fig. 1) indicates that the attacks
of bromine and acetate occurs by axial direction. It is worthwhile to mention
that no experimental evidence was sought to verify the assignments.
We also wish to provide a reasonable explanation for the formation of
compound 8. It is conceivable that compound 7 formed initially and then
under the reaction conditions or during workup underwent rearrangement to
dimethyl naphthalene 8 (Sch. 3).
Reaction of manganese(III) acetate and potassium bromide generates
Br† and OAc† radicals[7] which can add to the double bond of compound 3 yield-
ing compound 9. It is noteworthy that we isolate only one isomer of compound 9.

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Banerjee, Vera, and Laya
.
Scheme 2. Reagents: (i) (MeCO2)3 Mn 2H2O, KBr.
(1H NMR, the signals of CHBr, and CHOAc of the alternate isomer, would
appear in a region[8] completely different from that of compound 9).
In summary, we have achieved a viable synthesis of tetralone 4, an attrac-
tive intermediate for the preparation of occidol and emotin-G. The synthetic
route developed is short compared to the literature procedure,[1] which
involves many steps. Tetralone 2 can be easily prepared in high yield and
its conversion to tetralone 4 has been accomplished only in two steps. Further
the reactions involved are easily adaptable to large scale. These are the special
merits of the present work over the published report.[1]
Acetoxylation of tetralene 3 afforded two compounds 8 and 9 instead of
acetate 7, which was expected on the basis of previous work.[6] To the best
of our knowledge the formations of such side products during acetoxylation
of tetralin were never reported.
EXPERIMENTAL
Unless otherwise stated, IR spectra were taken on Nicolet FT and NMR
spectra recorded on a Brucker AM-390 spectrometer were taken in CDCl3.
Mass spectra were carried out on Dupont 21-492B. The expression workup
indicates that the solution was diluted with water, extracted with ether, washed
with brine, dried (MgSO4), and evaporated under reduced pressure. Column
chromatography was carried out on silica gel 60 (Merck) and TLC plates
were coated with silica gel and the spots were located by
exposing to UV light. Microanalyses were carried out in the Chemistry
Department, IVIC, Caracas.
5,8-Dimethyl-1-tetralone 2. To anhydrous AlCl3 (9.31 g, 69.7 mmol)
in p-xylene (20 mL) cooled to 158C under nitrogen, 4-chlorobutyric acid

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Synthesis of 5,8-Dimethyl-2-tetralone
2305
Figure 1. Molecular model of olefin 3.
(4 mL, 40.8 mmol) was added dropwise. The resulting suspension was stir-
red for 2 hr at room temperature, and further heated (45–508C) slowly for
1 hr. The resulting mixture was cooled, conc. hydrochloric acid (10 mL)
was added, and the mixture was extracted with chloroform. The organic
extract was washed several times with dil.sodium hydroxide (5%). The
alkaline extract was cooled to 108C, acidified with dil. hydrochloric acid
(10%) and extracted with chloroform. The workup yielded a brown liquid
which on distillation afforded acid 1 (7.21 g, 92%); bp 164–1688C
(1 mmHg); nmax/cm21 3400–2000 (OH), 1701 (CO); m/z 192 (Mþ,
82%), 132 (100, Mþ 2 MeCOOH); d 11.49 (1H, br, s, OH), 7.14–7.01
(2H, m, J ¼ 7.5 Hz), 6.88 (1H, s) (aromatic protons), 2.68 (2H, t,
J ¼ 7.5 Hz, C6H5CH2), 2.45 (2H, t, J ¼ 7.5 Hz, CH2COOH), 2.37 (6H, s,
2Me), 2.07–1.97 (m, 2H, CH2). (Found: C, 75.33; H, 10.31. C12H16O2
requires C, 74.97; H, 8.39%).
Colorless polyphosphoric acid (10 g, 100%, Aldrich) was stirred and
heated in an oil bath at 808C for 15 min. Acid 1 (2.01 g, 10.4 mmol) was
Scheme 3.

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Banerjee, Vera, and Laya
added dropwise. The mixture was heated at 100–1108C for 2 hr, the resulting
material was cooled and poured on cold water, and extracted with ether several
times. The combined ethereal extracts were washed with saturated
aq.NaHCO3 and dried. Removal of solvent and subsequent distillation
afforded the reported[4] tetralone 2 (1.74 g, 96%); bp 136–1388C (2 mmHg)
(Ref.[4] 160–1628C/1595 Pa); nmax/cm21 1674 (CO); m/z 174 (Mþ, 88%);
dH 7.16 (1H, d, J ¼ 7.5 Hz), 6.97 (1H, d, J ¼ 7.5 Hz) (ArH), 2.87 (2H, t,
J ¼ 6 Hz, CH2CO), 2.59 (3H, s), 2.28 (3H, s), (5,8-Me), and 2.08–1.99
(2H, m, CH2) (Found: C, 82.98; H, 8.28. C12H14O requires C, 82.72; H,
8.10%). [(Lit.[4] d 200 MHz) 2.90 (2H, t, J ¼ 7 Hz, CH2CO), 2.60 (3H, s,
Me), 2.28 (3H, s, Me)].
5,8-Dimethyl-1,2-dihydronaphthalene 3. A solution of tetralone 2
(1.21 g, 6.91 mmol), p-toluenesulfonic acid (35 mg), 2,4-pentanediol (3 mL,
27.6 mmol) in dry toluene (60 mL) was refluxed in a Dean–Stark water
separator for 48 hr. The reaction mixture was cooled to room temperature
(258C) and poured into dilute sodium bicarbonate solution (50 mL, 5%)
and extracted with toluene. The organic extract was washed several times
with saturated sodium chloride solution, dried, evaporated, and the residue
was distilled to obtain the dihydronaphthalene 3 (981 mg, 90%); as an oil,
bp 96–988C (1 mmHg); nmax/cm21 3100–3001 (ArH) and 1600 (C55C);
m/z 158 (Mþ. 100%); d 6.89–6.85 (2H, m, ArH), 6.76–6.71 (1H, dt,
J ¼ 9.8 Hz and 1.6 Hz); 6.16–6.13 (1H, dt, J ¼ 9.8 Hz and 4.1 Hz) (olefinic
protons, 1-H and 2-H), 2.78 (2H, t, J ¼ 8 Hz, 4-H) 2.36 (3H, s), and 2.31
(3H, s) (ArCH3) (Found: C, 91.35; H, 9.14. C12H14 requires C, 91.08; H,
8.92%).
5,8-Dimethyl-2-tetralone 4. To a solution of m-chloroperbenzoic acid
(Aldrich, 79% purity) (6.39 g, 28.5 mmol) in dichloromethane (70 mL),
cooled to 0–58C, was added dropwise a solution of compound 3 (3.09 g,
18.9 mmol) dissolved in dichloromethane (20 mL). The resulting mixture
was stirred at 0–58C for 6 hr and then filtered. The filtrate was washed
with dilute sodium hydroxide solution (50 mL, 10%), dried and evaporated
to yield an oil which was dissolved in ethanol (25 mL), treated with aqueous
sulphuric acid (25 mL, 60%), and heated (608C) for 3 hr. The dark brown
solution was diluted with water and extracted with ether. The workup
followed by chromatographic purification (hexane : Et2O 9 : 1) yielded the
reported[1] tetralone 4 (1.57 g, 46%); nmax/cm21 1716 (CO); m/z 174
(Mþ, 100%); 132 (81); dH 6.93 (2H, bs) (ArH), 3.53–3.49 (2H, m),
3.05–3.02 (2H, m) (1-H and 4-H), 2.62–2.57 (2H, m, 3-H), 2.33 (3H, s),
and 2.24 (3H, s) (ArMe) (Found: C; 82.91; H, 8.02. C12H14O requires C,
82.72; H, 8.10%). [(Lit[1] nmax/cm21 1710(CO); d (90 MHz) 2.08 (s, 3H)
(ArMe), 2.22 (s,3H) (ArH), 6.82 (bs, 2H) (ArH)].

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Synthesis of 5,8-Dimethyl-2-tetralone
2307
1,4-dimethylnaphthalene 8 and 5,8-dimethyl-1-acetoxy-2-bromo-
tetradihydronaphthalene 9. A solution of manganese(III) acetate dihydrate
(2.22 g, 8.3 mmol) in acetic acid (25 mL) was heated to 708C and olefin 3
(1.72 g, 10.8 mmol) and potassium bromide (112 mg) was added. The resulting
mixture was stirred at 708C for 6 hr, cooled, and then extracted with chloro-
form. The workup followed by chromatographic purification (hexane), gave
1,4-dimethylnaphthalene 8 (680 mg, 60%); bp 45–508C (2 mmHg) (bp
262–2648C, Aldrich); m/z 156 (Mþ, 100%); d 7.78 (2H, m), 7.38 (2H, m)
(ArH), 7.12 (2H, s) (ArH), and 2.72 (6H, s) (ArMe). Further elution
(hexane : Et2O 8 : 2) gave 9 (931 mg, 40%), mp 131–1338C (from Et2O);
nmax/cm21 1736 (CO); m/z 216 (Mþ-HBr, 26%), 174 (216 2 CH2CO,
100%), 159 (174 2 Me, 39%); dH 6.94 (1H, s), 6.91 (1H, s) (6-H and 7-H),
6.12 (1H, d, J ¼ 2.5 Hz), (CHOAc), 4.63(1H, q, J ¼ 2.6 Hz, CHBr), 2.33
(3H, s), 2.23 (3H, s) (ArMe), and 2.11 (3H, s, OAc) (Found: C, 56.85; H,
6.18. C14H17O2Br requires C, 56.56; H, 5.72%).
ACKNOWLEDGMENTS
The authors thank Professor Miguel E. Alonso, University of Los Andes,
Merida, Venezuela, for suggestions and comments to our work on acetoxyl-
´
ation. We also like to give thanks to Lic. P. Poon for discussions and reading
the manuscript.
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tetralon & 7-methoxy-1,4-dimethytetralol to emmotin G via their
Vilsmeier reaction. Indian J. Chem. 1981, 20B, 351.
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6. Gilmore, J.R.; Mellor, S.M. Oxidation of olefins by manganese(III) acetate
to give allylic acetates. J. Chem. Soc. 1971, 2355.

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7. Banerjee, A.K.; Vera, W.; Laya, M. Alternative procedure for the synthesis
of tavacpallescencine precursor. Russ. J. Org. Chem. 2002, 38, 855.
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Received in the USA March 3, 2004

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