Novel access to thioacylsilanes with benzotriazole-mediated methodology

Full text of DOI:10.1021/jo0011585

9206
J . Org. Chem. 2000, 65, 9206-9209
Notes
transformed into silyl sulfines and thioaldehyde S-
Novel Access to Th ioa cylsila n es w ith
Ben zotr ia zole-Med ia ted Meth od ology
oxides11 and be used as spin-trapping agents.12 Enethi-
olizable thioacylsilanes can afford 2-silyl thiacycloalkenes
or Z-R-silyl sulfides, convertable by protiodesilylation into
Z-vinyl sulfides, which are precursors of thioannulated
cyclopentenes and thiofunctionalized enones.13
Alessandro Degl’Innocenti* and Antonella Capperucci
Centro C.N.R. Composti Eterociclici e loro Applicazioni and
Dipartimento di Chimica Organica, via G. Capponi 9,
50121 Firenze, Italy
Novel routes to thioacylsilanes are of considerable
interest, and a general entry was recently reported, using
a hexamethyldisilathiane-based thionation procedure.14,15
We now present an alternative method for the generation
of thioacylsilanes using benzotriazole chemistry.
Daniela C. Oniciu
Alchem Laboratories Corporation,
13305 Rachael Boulevard, Alachua, Florida 32615
Alan R. Katritzky*
Center for Heterocyclic Compounds,
Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200
Resu lts a n d Discu ssion
1-(Benzotriazol-1-yl)-1-phenoxyalkanes 1 and 2 were
prepared as described previously (Scheme 1).16 1-(Ben-
zotriazol-1-yl)-1-methylthioalkanes 7a ,b,f,g were obtain-
ed from (benzotriazol-1-yl)methyl methyl thioether (6a )
by reactions with BuLi followed by alkyl halides or alde-
hydes, as described elsewhere.17 1-(Benzotriazol-1-yl)-1-
thioalkane derivatives 7c and 7e were prepared accord-
ing to known procedures.18-20 Reactions of derivatives 2
and 7a -e with BuLi and subsequent treatment with
trimethylchlorosilane afforded the -trimethylsilyl-benzo-
triazoles 3 and 8a -d , respectively (Schemes 1 and 2).
katritzky@chem.ufl.edu
Received J uly 31, 2000
In tr od u ction
Thioformyl- and thioacetyl-silanes are successful in-
termediates for thiocarbonyl-containing compounds,1-3
and useful building blocks for polyfunctionalized mol-
ecules. Besides being synthetic equivalents of thioalde-
hydes, thioacylsilanes4 are characterized by the high
reactivity of the carbon-sulfur double bond toward
nucleophiles, electrophiles, and cycloaddition reactions,
which lead to various compounds containing the Si-C-S
unit.5 Thus, thioacylsilanes react with organolithium
reagents to yield vinyl sulfides,6 and cycloadd to 1,3-
dipoles,6a,7 dienes,4,6b,8 heterodienes,9 and, under photo-
induced conditions, olefins.10 Silyl thioketones can be
Sch em e 1
(1) Capperucci, A.; Degl’Innocenti, A.; Scafato, P.; Spagnolo, P.
Phosphorus, Sulfur Silicon 1997, 120&121, 165.
(2) Capperucci, A.; Degl’Innocenti, A.; Scafato, P. in Recent Research
Developments in Synthetic Organic Chemistry; Pandalai, S. G., Ed.;
Transworld Research Network: India, 1998; p 171.
(3) Bonini, B. F.; Comes-Franchini, M.; Fochi, M.; Mazzanti, G.;
Ricci, A. J . Organomet. Chem. 1998, 567, 181. Bonini, B. F.; Fochi, M.
in Advances in Sulfur Chemistry; Rayner, C. M., Ed.; J AI: Stamford,
2000; Vol. 2, p 1.
(4) (a) Bonini, B. F.; Fochi, M. Rev. Heteroatom. Chem. 1997, 16,
46-67. (b) Bonini, B. F.; Comes-Franchini, M.; Fochi, M.; Mazzanti,
G.; Ricci, A.; Varchi, G. Tetrahedron Lett. 1999, 40, 6473-6476.
(5) Bonini, B. F. Phosphorus, Sulfur, Silicon 1993, 74, 31-45.
(6) (a) Bonini, B. F.; Mazzanti, G.; Zani, P.; Barbaro, G.; Battaglia,
A.; Giorgianni, P.; Maccagnani, G.; Macciantelli, D. J . Chem. Soc.,
Perkin Trans. 1 1986, 381-385. (b) Bonini, B. F.; Mazzanti, G.; Zani,
P.; Maccagnani, G. J . Chem. Soc., Perkin Trans. 1 1989, 2083-2088.
(c) Bonini, B. F.; Maccagnani, G.; Masiero, S.; Mazzanti, G.; Zani, P.
Tetrahedron Lett. 1989, 30, 2677-2680.
(11) Barbaro, G.; Battaglia, A.; Giorgianni, P.; Bonini, B. F.; Mac-
cagnani, G.; Zani, P. J . Org. Chem. 1990, 55, 3744-3748.
(12) (a) Alberti, A.; Bonini, B. F.; Pedulli, G. F. Tetrahedron Lett.
1987, 28, 3737-3740. (b) Alberti, A.; Benaglia, M.; Bonini, B. F.;
Pedulli, G. F. J . Chem. Soc., Faraday Trans. 1 1988, 84, 3347-3358.
(c) Alberti, A.; Benaglia, M.; Vismara, E. Res. Chem. Intermed. 1989,
11, 117-126.
(13) (a) Bonini, B. F.; Comes-Franchini, M.; Mazzanti, G.; Ricci, A.;
Rosa-Fauzza, C.; Zani, P. Tetrahedron 1996, 52, 4803-4816. (b) Bonini,
B. F.; Comes-Franchini, M.; Fochi, M.; Mazzanti, G.; Ricci, A. Tetra-
hedron Lett. 1994, 35, 9227-9228. (c) Bonini, B. F.; Comes-Franchini,
M.; Fochi, M.; Mazzanti, G.; Peri, F.; Ricci, A. J . Chem. Soc., Perkin
Trans. 1 1995, 2039-2044. (d) Bonini, B. F.; Comes-Franchini, M.;
Fochi, M.; Mazzanti, G.; Ricci, A. Tetrahedron 1997, 53, 7897-7910.
(14) (a) Degl’Innocenti, A.; Scafato, P.; Capperucci, A.; Bartoletti,
L.; Spezzacatena, C.; Ruzziconi, R. Synlett 1997, 361. (b) Ricci, A.;
Degl’Innocenti, A.; Capperucci, A.; Reginato, G. J . Org. Chem. 1989,
54, 19-20.
(7) Bonini, B. F.; Maccagnani, G.; Mazzanti, G.; Atwa, A. I. A.; Zani,
P. Heterocycles 1990, 31, 47-57.
(8) (a) Bonini, B. F.; Lenzi, A.; Maccagnani, G.; Barbaro, G.;
Giorgianni, P.; Macciantelli, D. J . Chem. Soc., Perkin Trans. 1 1987,
2643-2646. (b) Bonini, B. F.; Mazzanti, G.; Zani, P.; Maccagnani, G.
J . Chem. Soc. Chem. Commun. 1988, 365-367. (c) Bonini, B. F.; Busi,
F.; de Laet, R. C.; Mazzanti, G.; Thuring, J . W. J . F.; Zani, P.;
Zwanenburg, B. J . Chem. Soc., Perkin Trans. 1 1993, 1011-1018.
(9) (a) Carisi, P.; Mazzanti, G.; Zani, P.; Barbaro, G.; Battaglia, A.;
Giorgianni, P. J . Chem. Soc., Perkin Trans. 1 1987, 2647-2651. (b)
Bonini, B. F.; Masiero, S.; Mazzanti, G.; Zani, P. Tetrahedron Lett.
1991, 32, 2971-2974.
(15) Degl’Innocenti, A.; Capperucci, A.; Scafato, P.; Mecca, T.;
Reginato, G.; Mordini, A. Synlett 1999, 1739.
(16) Katritzky, A. R.; Lang, H.; Wang, Z.; Lie, Z. J . Org. Chem. 1996,
61, 7551.
(10) Bonini, B. F.; Comes-Franchini, M.; Fochi, M.; Mazzanti, G.;
Ricci, A.; Zani, P. J . Chem. Soc., Perkin Trans. 1 1995, 2039-2044.
10.1021/jo0011585 CCC: $19.00 © 2000 American Chemical Society
Published on Web 12/07/2000

Notes
J . Org. Chem., Vol. 65, No. 26, 2000 9207
Sch em e 2
Sch em e 3
Sch em e 4. P r op osed Mech a n ism for th e
F or m a tion of Com p ou n d s 11 a n d 12
Benzotriazole derivatives 3 and 8a -d reacted with
hexamethyldisilathiane (HMDST) in the presence of
TfOTMS or cobalt dichloride hexahydrate as a Lewis acid
to afford the corresponding thioacylsilanes 4 and 9a -d ,
which were trapped with 2,3-dimethyl-1,3-butadiene as
their adducts 5 and 10a -d (Schemes 1 and 2).
Reactions of the butyl, benzyl, and cyclopentyl deriva-
tives 8a -c afforded the corresponding silylated cycload-
ducts 10a -c in good yields upon treatment with HMDST
and 2,3-dimethyl-1,3-butadiene in the presence of CoCl2
(Scheme 2). However, the O-derivative 3 required the
addition of the more oxophilic TfOTMS to furnish the
cycloadduct 5 in 51% yield. By contrast, the use of
TfOTMS in the case of 8a led to mixtures of di(1-
trimethylsilyl-1-pentenyl)sulfide (11) and isomers of
1-trimethylsilyl-1-methylthio-1-pentene (12).
Earlier attempts to prepare bis-trimethylsilylthioke-
tone failed: no reactions of disilylated 1,3-dioxanes under
previously reported conditions14 have afforded a bis-silyl
thioketone. R-Bis(trimethylsilyl)benzotriazol-1-ylmethyl
methyl thioether (8d ) reacted smoothly with HMDST in
the presence of 2,3-dimethyl-1,3-butadiene and various
catalysts, such as CoCl2, TfOTMS, TiCl4, and even HCl
in methanol as a solvent. GC/MS analyses of the reaction
mixtures indicated that the bis(trimethylsilyl)dihydrothi-
opyran 10d was the sole or main product, but workup
led to its decomposition.
starting material. However, generation of the thioformyl-
silane 14 and its trapping with 2,3-dimethylbutadiene
to give adduct 15 was achieved efficiently by using HCl
in methanol as the solvent (Scheme 3).
As mentioned above, contrary to what was observed
in other cases, cyclohexadiene was inefficient as a trap-
ping agent in these reactions; in the case of the butyl
derivative 8a , it led to the formation of sulfide 11 as the
main product. Even the stronger Lewis acid TiCl4 with
8a and cyclohexadiene gave the isomeric olefin 12, arising
from benzotriazole elimination, as the only product
isolated. Scheme 4 depicts our rationalization of this
occurrence: reaction of the Bt-derivative 8a in the
present conditions affords initially thioacylsilane 9a ,
which further reacts as its enethiol 9a ′, through a
carbophilic pathway, with more 9a to afford adduct 16.
This pathway was previously described in the literature.4a
Compound 16, upon loss of H2S, gives the isolated divinyl
sulfide 11. The isomers of 1-trimethylsilyl-1-methylthio-
1-pentene (12) arise from benzotriazole elimination in the
starting material (Scheme 4).
Interestingly, compound 13 was rather inert in the
present reaction conditions. Thus, attempted reactions
of 13 with HMDST in the presence of CoCl2, TfOTMS,
or even BF3 etherate or TiCl4 led only to recovery of
As documented in the Experimental Section, upon
standing, the 1-(benzotriazol-1-yl) pent-1-yl ether 8a
partially rearranged into the corresponding (1-benzo-
triazol-2-yl)pent-2-yl analogue. Such rearrangement be-
tween isomeric pairs of compounds of type RX-CH(R1)-
Bt1 / RX-CH(R1)-Bt2 are common.21-25 However, such
(17) Katritzky, A. R.; Oniciu, D. C.; Ghiviriga, I.; Soti, F. J . Org.
Chem. 1998, 63, 2110.
(18) Katritzky, A. R.; Ghiviriga, I.; Oniciu, D. C.; Soti, F. J .
Heterocycl. Chem. 1996, 33, 1927.
(19) Katritzky, A. R.; Perumal, S.; Kuzmierkiewicz, W.; Lue, P.;
Greenhill, J . V. Helv. Chim. Acta 1991, 74, 1924.
(20) Katritzky, A. R.; Afridi, A. S.; Kuzmierkiewicz, W. Helv. Chim.
Acta 1991, 74, 1931.
(21) Smith, J . L. R.; Saad, J . S. J . Chem. Soc., Perkin Trans. 1 1975,
1181.

9208 J . Org. Chem., Vol. 65, No. 26, 2000
Notes
Ta ble 1. Su m m a r y of Resu lts
(60 and 200 MHz) or the solvent as the internal standard for
13C (22.5 and 50 MHz). Tetrahydrofuran was distilled under
nitrogen immediately prior to use from sodium/benzophenone.
All reactions with air-sensitive compounds were carried out
under an argon atmosphere. Column chromatography was
conducted with silica gel 230 mesh. TLC was performed on
precoated silica gel 60 F254 plates. Benzotriazol-1-ylalkyl phenyl
ethers 1-3 and 13 were prepared according to the literature
procedures.16 (Benzotriazol-1-yl)methyl methyl thioether (6a )17
and benzotriazole derivatives 7a -g18-20 were prepared by the
procedures previously reported.
2-Meth yl-2-tr im eth ylsilyl-4,5-d im eth yl-3,6-d ih yd r o-2H-
th iop yr a n (5). A mixture of 1-(benzotriazol-1-yl)-1-phenoxy-1-
trimethylsilylethane (3) (30 mg, 0.1 mmol), 2,3-dimethyl-1,3-
butadiene (41 mg, 0.5 mmol), and HMDST (36 mg, 0.2 mmol) in
0.5 mL of CH3CN was treated at room temperature with CF3-
SO3SiMe3 (0.02 mmol, 5 µL) under inert atmosphere. Progress
of the reaction was monitored by GC/MS analysis. After 6 h the
reaction mixture was quenched with saturated NH4Cl, extracted
with diethyl ether, and dried over Na2SO4. After removal of the
solvent, the product was purified by chromatography on silica
gel (cyclohexane) affording 11 mg of pure product (51%). 1H NMR
(CDCl3, 200 MHz) δ: 0.08 (s, 9 H), 1.28 (s, 3 H), 1.66 (bs, 3 H),
1.72 (bs, 3 H), 1.76 (bd, 1 H, partially overlapped with peak at
1.72 ppm), 2.44 (bd, 1 H), 2.71 (bd, 1 H), 3.26 (bd, 1 H). 13C NMR
(CDCl3, 50 MHz) δ: -4.3, 19.7, 20.8, 21.6, 26.4, 36.9, 39.9, 122.1,
125.2. MS m/z (%): 214 (M+, 1), 199 (2), 141 (9), 109 (25), 108
(100), 92 (28), 73 (80). Anal. Calcd for C11H22SSi: C, 61.61; H,
10.34. Found: C, 61.52; H, 10.42.
Gen er a l P r oced u r e for th e Silyla tion of r-Ben zotr ia z-
olyla lk yl Th ioeth er s 7a -d . To a solution of the appropriate
(benzotriazol-1-yl)methyl derivative (50 mmol) in THF (200 mL)
at -78 °C under nitrogen was added BuLi (2.22 M in hexane,
23.6 mL, 52.5 mmol) over a period of 5 min. After 10 min, a
solution of trimethylchlorosilane (60 mmol) in THF (10 mL) was
added. The mixture was stirred at -78 °C for 2 h and then was
allowed to warm to room temperature and stirred for an
additional 12 h. The reaction was quenched with saturated
ammonium chloride (100 mL) and extracted with methylene
chloride (3 × 50 mL), and the combined extracts were washed
with water (2 100 mL) and dried (MgSO4). After the solvent was
removed by rotary evaporation, the residue was subjected to
column chromatography to give the pure product.
isomerization is of little significance from a purely
preparative point of view, as Bt1 and Bt2 isomers of type
RX-CH(R1)-Bt show essentially similar reactivity, par-
ticularly in reactions involving ion pair intermediates of
type RX+dCHR1Bt-.
1-(Ben zot r ia zol-1-yl)-1-t r im et h ylsilylp en t -1-yl Met h yl
Th ioeth er (8a ). 1-(Benzotriazol-1-yl)pent-1-yl methyl thioether
(7a ) (2.35 g, 10 mmol) was dissolved in 50 mL of THF, and a
solution of BuLi 2 N in hexane (5.25 mL, 10.5 mmol) was added
at -78 °C under nitrogen and with stirring. Ten minutes later,
trimethylsilyl chloride (1.20 g, 1.40 mL, 11 mmol) was added,
and the reaction mixture was stirred at -78 °C for 2 h and at rt
for 12 h. The reaction was quenched with 100 mL of sodium
chloride 5%. The layers were separated, and the aqueous layer
was extracted with diethyl ether (3 25 mL). The combined
organic extracts were dried over magnesium sulfate, and the
solvent was removed in vacuo. The residue (3.01 g) was flash
chromatographed on silica gel (175 g) eluting with benzene:ethyl
acetate 95:5. The expected product was separated as an oil (2.54
g) in 84% yield. It partially rearranged on standing at room
temperature to the Bt-2 isomer: 1H NMR 0.35 (s, 9 H), 0.95 (t,
J ) 7.4 Hz, 3 H), 1.20-1.50 (m, 4 H), 2.10 (s, 3 H), 2.15-2.25
(m, 2 H), 7.30-7.40 (m, 2 H), 7.70-7.80 (m, 2 H). Distinct signals
of the Bt-1 isomer (20%): 0.45 (s, 1 H), 0.80 (t, J ) 7.2 Hz, 3 H),
7.35-7.45 (m, 2 H), 8. 10 (d, J ) 8.2 Hz, 2 H), 8. 20 (d, J ) 8.2
Hz, 2 H); 13C NMR 0.91, 13.1, 15.5, 24.7, 29.7, 38.1, 70.6, 115.5,
119.7, 121.8, 127.4, 135.2, 145.2.
Con clu sion s
Table 1 summarizes the experimental results. The
methodology described in this paper provides a general
method for the synthesis of silylated thiocarbonyl com-
pounds, and represents an extension to the synthesis of
silylated thioaldehydes by the reaction of hexamethyl-
disilathiane with silyl acetals.14 The pathway described
above enables the direct preparation of silylated thioke-
tones and eliminates the tedious synthesis of their silyl
acetal precursors. Other significant advantages of the
present methodology over previous methods include the
readily available starting materials and simple proce-
dures.
Exp er im en ta l Section
Gen er a l. Melting points were determined with a hot-stage
apparatus and are uncorrected. NMR spectra were recorded in
CDCl3 with tetramethylsilane as the internal standard for 1H
Gen er a l P r oced u r e for th e Syn th esis of Th ioa cylsila n e
Ad d u cts 10a -d Sta r tin g fr om 1-(Ben zotr ia zol-1-yl)-1-tr i-
m eth ylsilylm eth yl Th ioeth er s 8a -d . A solution containing
the appropriate 1-(benzotriazol-1-yl)-1-trimethylsilyl methyl
thioether (0.1 mmol), 2,3-dimethyl-1,3-butadiene (0.5 mmol), and
HMDST (0.2-0.4 mmol) in CH3CN (0.5 mL) was treated at room
temperature in inert atmosphere with a solution of CoCl2‚6H2O
(0.1 mmol) in CH3CN (0.5 mL). Progress of the reaction was
monitored by GC/MS analysis. The reaction mixture was
quenched with saturated NH4Cl, extracted with diethyl ether,
and dried (Na2SO4) and the solvent removed under vacuum. The
(22) Katritzky, A. R.; Yannakopoulou, K.; Kuzmierkiewicz, W.;Au-
rrecoechea, J . M.; Palenik, G. J .; Koziol, A. E.; Szczesniak, M.;
Skarjune, R. J . Chem. Soc., Perkin Trans. 1 1989, 225.
(23) Katritzky, A. R.; Rachwal, S.; Rachwal, B.; Steel, P. J . J . Org.
Chem. 1992, 57, 4932.
(24) Katritzky, A. R.; Kuzmierkiewicz, W.; Perumal, S. Helv. Chim.
Acta 1991, 74, 1936.
(25) Katritzky, A. R.; Perumal, S.; Fan, W.-Q. J . Chem. Soc., Perkin
Trans. 2 1990, 2059.

Notes
J . Org. Chem., Vol. 65, No. 26, 2000 9209
crude product was then purified by preparative TLC on silica
gel using hexane as an eluent.
(4), 150 (19), 107 (31), 95 (35), 73 (100). Anal. Calcd for C14H28
SSi: C, 65.55; H, 11.00. Found: C, 65.40; H, 11.12.
-
2-Bu t yl-2-t r im et h ylsilyl-4,5-d im et h yl-3,6-d ih yd r o-2H -
th iop yr a n (10a ). Following the general procedure, starting from
30 mg (0.1 mmol) of 8a , 16 mg of pure 10a were obtained (64%).
1H NMR (CDCl3, 200 MHz) δ: 0.09 (s, 9H), 0.89 (bt, 3H), 1.25-
1.33 (m, 4H), 1.51-1.55 (m, 2H), 1.67 (bs, 3H), 1.71 (bs, 3H),
1.89 (bd, 1H), 2.41 (bd, 1H), 2.68 (bd, 1H), 3.12 (bd, 1H). 13C
NMR (CDCl3, 50 MHz) δ: -2.7, 14.0, 19.4, 20.7, 23.5, 26.9, 28.8,
30.2, 35.3, 38.6, 122.3, 125.5. MS m/z (%): 256 (M+, 0.1), 183
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and 1H and 13C NMR and GC/MS spectral data for
compounds 8b-d , 10b-d , 13, and 15. This material is
available free of charge via the Internet at http://pubs.acs.org.
J O0011585