Addition of thio compounds to (R)-limonene catalyzed by amberlyst-15

Article abstract of DOI:10.1080/10426500490459849

The addition of thioacids and thiophenol to (R)-limonene catalyzed by Amberlyst-15 produced the corresponding 9-thioester- or 9-thioether-p-menthene chemo- and regioselectively.

Full text of DOI:10.1080/10426500490459849

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Phosphorus, Sulfur, and Silicon and the Related
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ADDITION of THIO COMPOUNDS to (R)-LIMONENE
CATALYZED by AMBERLYST-15
Marcio C. S. Mattos a & Antonio M. Sanseverino a
a Universidade Federal do Rio de Janeiro , Rio de Janeiro, Brazil
Published online: 16 Aug 2010.
To cite this article: Marcio C. S. Mattos & Antonio M. Sanseverino (2004) ADDITION of THIO COMPOUNDS to (R)-
LIMONENE CATALYZED by AMBERLYST-15, Phosphorus, Sulfur, and Silicon and the Related Elements, 179:6, 1203-1208, DOI:
10.1080/10426500490459849
To link to this article: http://dx.doi.org/10.1080/10426500490459849
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Phosphorus, Sulfur, and Silicon, 179:1203–1208, 2004
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ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490459849
ADDITION OF THIO COMPOUNDS TO
(R)-LIMONENE CATALYZED BY AMBERLYST-15
Marcio C. S. de Mattos and Antonio M. Sanseverino
Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
(Received May 15, 2003; accepted October 15, 2003)
The addition of thioacids and thiophenol to ( R)-limonene catalyzed by
Amberlyst-15 produced the corresponding 9-thioester- or 9-thioether-p-
menthene chemo- and regioselectively.
Keywords: Amberlyst-15; ion-exchange resin; limonene; thioether;
thioester
The catalyzed addition of thio compounds to alkenes can be with
Markovnikov (using montmorillonite K-10,1 Lewis,2 or protic acids3)
or anti-Markovnikov (using zeolites4 or radical conditions5) selectivity.
Thio compounds derived from limonene are used as flavors or flota-
tion agents.6 The uncatalyzed reaction of thioacetic acid with limonene
(1) is not chemoselective, producing a mixture of addition products to
both double bonds along with diaddition products.7 On the other hand,
the reaction of limonene with thiols catalyzed by boron trifluoride pro-
duces the 9-thio derivatives,8 whereas the reaction of thiophenol cat-
alyzed by HClO4 produces in low yield the 8-thio derivative of difficult
purification9 (Scheme 1).
Continuing our interest in chemo- and regiospecific functionalization
of the 8,9-double bond of (R)-limonene,10 we studied the reaction of
diverse thio compounds catalyzed by Amberlyst-15, a macroreticular
strong acidic sulfonic ion-exchange resin (H0 = −2.2),11 and present
our results here.
RESULTS AND DISCUSSION
The reaction of (R)-limonene (10 mmol) with thioacetic acid (10 mmol)
in dichloromethane at room temperature and catalytic Amberlyst-15
We thank Elizabeth R. Lachter for the kindly donation of Amberlyst-15, and W. Bruce
Kover and David E. Nicodem for helpful discussions. AMS thanks CNPq for a fellowship.
Address correspondence to Marcio C. S. de Mattos, Departamento de Qu´ımica,
Orgaˆnica, Instituto de Qu´ımica, Universidade Federal do Rio de Janeiro, Caixa Postal
68545, 21945-970, Rio de Janeiro, Brazil. E-mail: mmattos@iq.ufrj.br
1203

1204
M. C. S. de Mattos and A. M. Sanseverino
SCHEME 1
(ca. 5% in weight) led to a product 2a along with some unreacted sub-
strate (determined by high-resolution gas chromatography). After low-
pressure distillation, 2a was isolated in 73% yield and its MS spectra
indicated incorporation of one unit of thioacetic acid to limonene (m/z
212 and 214). The IR spectra of the product showed characteristic sig-
nals of thioesters (1693, 1135, and 1109 cm−1) and the disappearance of
the signal of the disubstituted double bond of limonene (890 cm−1), in-
dicating a chemoselectivity to the acyclic double bond of the substrate.
The 1H NMR spectra showed two multiplets at 2.76 and 3.04 ppm (1H
each) of a CH2 linked to thioester, indicating both an anti-Markovnikov
addition and a diastereoisomeric mixture of products. The fact the 2a is
a pair of diastereoisomers (ca. 1:1) is confirmed by two signals of methyl
at 1.70 and 1.71 ppm. The 13C NMR spectrum showed a mixture of di-
astereoisomers too, as there were many signals with very close shifts
(e.g., ring CH at 120.6 and 120.8 ppm, CH3 of isopropyl at 15.9 and
16.3 ppm). Based on these informations the proposed structure for 2a
is shown in Figure 1.
To our surprise, an anti-Markovnikov product was obtained and
it was unexpected, because its formation is consistent with a radical
process.5 Furthermore, the addition of alcohols to limonene catalyzed
by Amberlyst-15 produced regioselectively the 8-substituted terpinyl

Addition of Thio Compounds to (R)-Limonene
1205
FIGURE 1 Selected NMR data for 2a (mixture of diastereoisomers).
ethers.12 Control experiments with freshly distilled limonene,13,∗ rig-
orous exclusion of air, or reaction in the presence of free radicals
inhibitors14 led to the same product 2a in similar yield. On the
other hand, in the absence of the catalyst, the reaction of limonene
with thioacetic acid was incomplete after several hours, producing the
thioester 2a in low yield along with unreacted substrate (in our hands
no mixture of several products was detected as previously described7).
A possible explanation for the formation of the anti-Markovnikov
product could be an initial complexation of limonene with the resin. In
analogy to the case with zeolites,4 due to steric constraints the bulkier
Markovnikov adduct could not be retained in the resin and the attack of
the thioacid occurs at the less hindered primary carbon of the complex,
producing the anti-Markovnikov product.
Based on the above results, it was decided to demonstrate the gener-
ality and utility of the Amberlyst-15 catalyzed reaction of (R)-limonene
with other thio compounds. In all cases the corresponding 9-thio-p-
menthenes were obtained as a ca. 1:1 mixture of diastereoisomers
(Table I summarizes the results).
The reaction of (R)-limonene with thiobenzoic acid produced the
thioester 2b in 65% isolated yield after 20 h [methylene adjacent to
thioester at 2.73 and 3.03 ppm (m, 1H each)]. The reaction of (R)-
limonene with thiophenol produced the thioether 2c in 51% isolated
yield [methylene adjacent to thioester at 2.75 and 3.06 ppm (m, 1H
each)] along with unreacted limonene (ca. 30% recovered), diphenyld-
isulphide (ca. 5%) and diaddition products (ca. 10%).
On the other hand, the reactions of (R)-limonene with 1-propanethiol
and 2-propanethiol were disappointing as the substrate was recovered
∗It is known that limonene produces peroxides quickly.

1206
M. C. S. de Mattos and A. M. Sanseverino
TABLE I Yields of 2 Obtained
Entry
R
Time (t/h)
Yield of 2 (%)a
a
b
c
d
e
CH3C(O)
PhC(O)
Ph
Pr
i-Pr
18
20
48
>60
>48
73
65
51
b
—
b
—
aYield of pure product based on limonene.
bLimonene recovered.
and no product was detected by the analytical techniques employed
1
(high-resolution gas chromatography, H and 13C NMR spectroscopy).
Several attempts to perform the reaction changing the conditions (re-
action time, temperature, and addition of more catalyst) proved unsuc-
cessful too.
The fact that thiophenol added to limonene while alkylthiols fail-
ured could be explained in terms of the proton affinity of these thio
compounds. The proton affinity of alkylthiols is 3 kcal/mol higher than
thiophenol (189.3 vs 186.3 kcal/mol15) and consequently the more ba-
sic∗ alkylthiols could be protonated by the acidic resin (H0 = −2.211).
Hence, a nucleophilic attack of thiophenol to the limonene-resin com-
plex is possible while protonated alkylthiols do not react at all.
In summary, we have developed a very attractive route to 9-thio-p-
menthanes. As in the case of related monoterpene sulfides,16 the prod-
ucts offer great potentials as starting materials for multistep prepara-
tion of bisabolanes.
EXPERIMENTAL
(R)-Limonene (Dierberger) was distilled at 177◦C (lit.17 178◦C) and
stored in a freezer. Amberlyst-15 (Rohm & Haas), thio compounds
∗As the solvent (CH2Cl2) does not efficiently solvate the thiols, the basicity in the gas
phase can be assumed to be the same as in solution.

Addition of Thio Compounds to (R)-Limonene
1207
(Aldrich) and other chemicals were used without further purifica-
1
tion. H NMR and 13C NMR spectra were acquired on a Bruker AC-
200 (200 MHz and 50 MHz respectively) spectrometer in CDCl3 solu-
tions with TMS as internal standard. IR spectra were recorded on a
Perkin-Elmer 1600 FT-IR spectrometer (KBr film). MS were obtained
on a Hewlett-Packard HP 5896-A HRGC-MS using electron impact
(70 eV). Analyses by high-resolution gas chromatography were per-
formed on a HP 5890-II gas chromatograph with FID by using a 25
m (length), 0.53 mm (ID) and 0.50 µm (phase thickness) RTX-5 silica
capillary column (Restek Co.) and He (flow rate 50 cm/s) as carrier gas
(split 1:20).
General Procedure for the Addition of Thio Compounds
to Limonene Catalyzed by Amberlyst-15
To a stirred solution of (R)-limonene (10 mmol) and the thio compound
(10 mmol) in CH2Cl2 (25 ml) was added Amberlyst-15 (70 mg) at room
temperature. After the time shown in Table I, the catalyst was filtered
off and washed with CH2Cl2 (10 ml). The combined liquid was washed
with water (10 ml), 5% NaHCO3 (10 ml), water (10 ml) and then dried
(Na2SO4). After evaporation of the solvent, the residue was distilled at
reduced pressure.
(2RS, 3ꢀR)-1-[4ꢀ-Methylcyclohex-3ꢀ-enyl)propylthio]ethan-
1-one (2a) ca. 1:1 Mixture of Diastereoisomers
It was obtained 1.54 g (73%), b.p. 120–122◦C/1 Torr. δH 0.92 (m, 3H),
1.25 (m), 1.70 (s, CH3), 1.71 (s, CH3), 2.35 (s), 2.76 (m, 1H), 3.04 (m,
1H), 5.37 (broad s, 1H) ppm. δC 15.9, 16.3, 23.6, 25.5, 27.3, 27.8, 29.4,
30.4, 30.6, 30.8, 34.1, 34.3, 37.8, 37.9, 38.0, 120.5, 120.6, 134.2, 196.3
ppm. νmax 2961, 2924, 2836, 1693, 1451, 1354, 1135, 1109, 955, 800, 629
cm−1. m/z 214 (M++2), 212 (M+), 173, 171, 136 (100%), 123, 121, 107,
94, 79.
(2RS, 3ꢀR)-2-(4ꢀ-Methylcyclohex-3ꢀ-enyl)propylthio Phenyl
Ketone (2b) ca. 1:1 Mixture of Diastereoisomers
◦
It was obtained 1.75 g (65%), b.p. 185–187 C/1 Torr. δH 1.03 (m,
3H), 1.61–1.84 (m), 1.70 (s, CH3), 1.92–1.96 (m), 2.73 (m, 1H), 3.03
(m, 1H), 5.37 (broad s, 1H), 7.45–8.00 (m) ppm. δC 16.1, 23.6, 30.4, 30.6,
31.6, 34.2, 38.2, 38.3, 38.4, 41.4, 120.2, 120.3, 128.7, 129.7, 131.1, 137.3,
137.7, 139.3, 197.0 ppm.

1208
M. C. S. de Mattos and A. M. Sanseverino
(2RS, 3ꢀR)-2-(4ꢀ-Methylcyclohex-3ꢀ-enyl)propylthio]benzene
(2c) ca. 1:1 Mixture of Diastereoisomers
It was obtained 1.24 g (51%), b.p. 150–153◦C/1 Torr. δH 1.00 (dd), 1.63
(s, CH3), 1.77 (m), 2.75 (m, 1H), 3.06 (m, 1H), 5.36 (broad s, 1H), 7.29
(m) ppm. δC 15.9, 16.4, 23.6, 25.5, 29.7, 30.8, 30.9, 37.3, 37.4, 39.0, 39.1,
120.8, 127.3, 129.0, 129.2, 137.2, 137.7, 196.2 ppm. m/z 248 (M+ + 2),
246 (M+), 136 (100%), 123, 107, 94, 79.
REFERENCES
[1] S. Kanagasabapathy, A. Sudalai, and B. C. Benicewicz, Tetrahedron Lett., 42, 3791
(2001).
[2] M. Belley and R. Zamboni, J. Org. Chem., 54, 1230 (1989).
[3] C. G. Screttas and M. Micha-Screttas, J. Org. Chem., 44, 713 (1979).
[4] P. Kumar, R. K. Pandey, and V. R. Hedge, Synlett, 1921 (1999).
[5] K. Griesbaum, Angew. Chem. Int. Ed. Engl., 9, 273 (1970).
[6] A. F. Thomas and Y. Bessiere, Nat. Prod. Rep., 6, 291 (1989).
[7] G. R. Davletina, E. K. Kazakova, and S. G. Vul’fson, Zh. Org. Khim., 29, 1632 (1993).
[8] V. A. Morgunova, L. E. Nikitina, V. V. Plemenkov, M. G. Fazylaeva, and Y. B.
Chugunov, Russ. J. Org. Chem., 36, 489 (2000).
[9] J. D. Fourneron, L. M. Harwood, and M. Julia, Tetrahedron, 38, 693 (1982).
[10] a) M. C. S. de Mattos, R. B. Coelho, and A. M. Sanseverino, Synth. Commun., 34,
541 (2004); b) M. C. S. de Mattos, S. P. L. de Souza, and S. M. Elias, Heterocycl.
Commun., 9, 247 (2003); c) M. C. S. de Mattos, S. P. L. de Souza, and S. M. Elias,
Heterocycl. Commun., 7, 249 (2001); d) A. M. Sanseverino, M. C. S. de Mattos, and
W. B. Kover, J. Chem. Res. (S), 346 (2000).
[11] J. Tejero, F. Cunill, M. Iborra, J. F. Izquierdo, and C. Fite´, J. Mol. Catal. A: Chem.,
182–183, 541 (2002).
[12] M. J. L. Rao, S. Nagarajan, and K. N. Gurudutt, J. Sci. Ind. Res., 58, 682 (1999).
[13] W. F. Newhall, J. Org. Chem., 23, 1274 (1958).
[14] E. T. Denisov and I. V. Khudyakov, Chem. Rev., 87, 1313 (1987).
[15] G. A. DiLabio, D. A. Pratt, A. D. LoFaro, and J. S. Wright, J. Phys. Chem. A, 103,
1653 (1999).
[16] O. Smitt and H.-E. Hogberg, J. Chem. Res. (S), 527 (2002).
[17] R. C. Weast (Ed.), Handbook of Chemistry and Physics (CRC Press, Boca Raton,
1985), 65th ed.