Direct formation of α,β-unsaturated dithioacetals from diarylpropynols

Article abstract of DOI:10.1016/j.tetlet.2010.12.021

The acid-catalysed condensation of a series of 1,1-diarylprop-2-yn-1-ols with 2-thionaphthol unexpectedly gave 3,3-diaryl-1,1-bis(2-naphthylthio)prop-2- enes in good yields via a Meyer-Schuster-type rearrangement.

Full text of DOI:10.1016/j.tetlet.2010.12.021

Tetrahedron Letters 52 (2011) 708–710
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Direct formation of
a,b-unsaturated dithioacetals from diarylpropynols
⇑
Ashley J. Curtis, Christopher D. Gabbutt, B. Mark Heron , Colin Kilner
School of Chemistry, University of Leeds, Leeds LS2 9JT, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
The acid-catalysed condensation of a series of 1,1-diarylprop-2-yn-1-ols with 2-thionaphthol unexpect-
edly gave 3,3-diaryl-1,1-bis(2-naphthylthio)prop-2-enes in good yields via a Meyer–Schuster-type
rearrangement.
Received 14 October 2010
Revised 19 November 2010
Accepted 3 December 2010
Available online 9 December 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Dithioacetal
Prop-2-yn-1-ols
Propargylic alcohol
Meyer–Schuster rearrangement
Substituted prop-2-yn-1-ols (propargyl alcohols) are versatile
substrates in organic synthesis enabling access to carbocyclic sys-
tems,1 macrocycles,2 heterocycles3 and transition metal com-
has apparently been overlooked.15 In this Letter we report our ini-
tial observations concerning the acid-catalysed reaction between
2-thionaphthol and a series of 1,1-diarylprop-2-yn-1-ols.
R2 R3
Ar
R1
R1
Ar
Ar
R1
O
O
O
HO
Ar
Ar
R1 Ar
Ar
Ar
Ar
Ar
1
2
3
4
5
plexes.4 Their Meyer–Schuster rearrangement5 results in the
formation of a variety of
,b-unsaturated carbonyl compounds6–8
Heating a stirred equimolar mixture of 2-thionaphthol and 1,1-
a
bis(4-dimethylaminophenyl)prop-2-yn-1-ol (1a) under reflux in
toluene containing suspended acidic alumina, the conditions
which routinely afford naphthopyrans from naphthols, gave after
ca. 2 h, a complex reaction product that contained a major new
component (TLC). Elution of the crude dark red reaction product
from silica gave a single pure product as pale lilac crystals, the
structure of which could not be assigned from routine 1H and 13C
NMR and infrared spectroscopic data. 1H NMR spectroscopy re-
vealed the presence of an AB system (d 5.47, d, 1H and d 5.90, d,
1H) with J = 10.7 Hz and two NMe2 signals at d 2.90 and d 2.97
(each 6H).16 HRMS provided a molecular ion m/z = 597.2389 which
was indicative of a condensate derived from two 2-naphthylthio
units and one propynol 1a, and was clearly not the naphthothiopy-
ran 6. X-ray analysis of a single crystal revealed the dithioacetal
structure 7a (Fig. 1).17
and their Sonogashira reaction with aryl bromides has been shown
to proceed directly to chalcones.9 1,1-Diarylprop-2-yn-1-ols 1 are
key precursors to tetrasubstituted naphthacenes 2 which play an
important role in the molecular electronics arena.10 Treatment of
1 (R1 = H), with acid leads to intensely coloured cationic dyes 3,11
and their acid-catalysed condensation with acidic methylene com-
pounds affords interesting merocyanines 4.12 Our interest stems
from the behaviour of 1 towards naphthols under acidic catalysis
which notably provides access to a diverse range of commercially
important photochromic naphthopyrans 5.13 Whilst a broad range
of substituted 1- and 2-naphthols and carbocyclic- and heterocy-
clic-fused naphthols has been employed in this reaction to afford
structurally diverse naphthopyrans,14 the related reaction of
thionaphthols with 1 to afford presumably naphthothiopyrans 6
The foregoing reaction was repeated employing a reactant ratio
of 2:1 of 2-thionaphthol/propynol 1a which resulted in a 69%
isolated yield of 7a after chromatography and recrystallisation.
⇑
Corresponding author. Tel.: +44 (0) 113 3432925.
E-mail address: b.m.heron@leeds.ac.uk (B. Mark Heron).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.12.021

A. J. Curtis et al. / Tetrahedron Letters 52 (2011) 708–710
709
Figure 1. X-ray crystal structure of 7a (thermal ellipsoids at 50% probability level).
Two further propynols, 1b and 1c, were also examined and gave
related dithioacetals 7b (54%) and 7c,d (combined yield 61%),
respectively (Scheme 1).16 Notably, products 7c and 7d derived
from the unsymmetrically substituted propynol 1c were obtained
as an inseparable mixture of approximately equal amounts of
geometrical isomers, as indicated by the presence of two AB sys-
tems with doublets at ca. d 5.4 and d 5.9 with coupling constants
comparable to those of 7a. The higher field doublet (ca. d 5.4) in
the 1H NMR spectrum of 7a–d was assigned to the methine proton
by comparison with data for the known dithioacetal, (E)-1-phenyl-
3,3-bis(phenylthio)propene in which the methine proton resonates
at d 5.01 and the vinyl proton at d 6.19.18
SNp
Ar
+H+, -H2O
HO
+NpSH
-H+
•
Ar
Ar
Ar
Ar
Ar
1
8
9
+H+
SNp
SNp
SNp
+NpSH, -H+
A postulated mechanism for the formation of 7 is depicted in
Scheme 2 and has similarity to the Meyer–Schuster rearrange-
ment.5 Protonation and elimination of water from the propynol 1
affords the cation 8 which is intercepted by 2-thionaphthol to
afford the allenyl thioether 9,19 protonation of which generates
Ar
Ar
Ar
Ar
10
7
Scheme 2. Postulated mechanism for the formation of compounds 7.
X
SNp
HO
SNp
(i)
(i)
X
Y
S
Y
X
Y
1a
7a
= X = Y = NMe2
= X = Y = NMe2
1b = X = Y = OMe
7b = X = Y = OMe
1c = X = NMe2, Y = OMe
6
7c
= X = NMe2, Y = OMe
7d = X = OMe, Y = NMe2
Reagents and conditions: (i) 2-thionaphthol (NpSH), acidic Al2O3, PhMe, reflux
Scheme 1. Preparation of dithioacetals 7.

710
A. J. Curtis et al. / Tetrahedron Letters 52 (2011) 708–710
toluene (70 mL) was warmed to 50 °C. Acidic alumina (3.0 g, acidic
Brockmann 1, activated, 150 mesh) was added and the mixture was heated
under reflux until examination of the reaction mixture by TLC indicated that no
further reaction had occurred (ca. 2 h). The cooled mixture was filtered and the
spent alumina catalyst was washed with warm toluene (2 Â 50 mL). Removal
of the toluene from the combined washings and filtrate gave a dark red gum
that was eluted from silica with 30% CH2Cl2 in hexane to afford: 3,3-bis(4-
thionium ion 10. Addition of a second mole of 2-thionaphthol and
elimination of H+ completes the sequence.
The transformation of 1 into 7, the formal product of dithioace-
tal formation from a 3,3-diarylprop-2-enal with 2-thionaphthol, is
unusual. The acid-catalysed condensation of a,b-unsaturated alde-
hydes with thiophenols and thionaphthols is not straightforward.
For example, treatment of cinnamaldehyde with 4-toluenethiol
in 1,2-dichloroethane containing 4-TsOH affords 4-arylthio-3,4-
dihydro-2H-[1]benzothiopyrans,20 whereas addition of thiophenol
to cinnamaldehyde, either under solvent-free catalysis with
dimethylaminophenyl)-1,1-bis(2-naphthylthio)prop-2-ene
(7a),
as
lilac
microcrystals from hexane/CH2Cl2, 69% (5.11 g), mp 123–124 °C, mmax (neat)
2886, 2801, 1608, 1588, 1516, 1353, 1195, 1063, 945, 808, 739, 471 cmÀ1, dH
(400 MHz) 2.90 (6H, s, NMe2), 2.97 (6H, s, NMe2), 5.47 (1H, d, J = 10.7 Hz, 1-H),
5.90 (1H, d, J = 10.7 Hz, 2-H), 6.52 (2H, m, Ar-H), 6.58 (2H, m, Ar-H), 6.96 (4H,
m, Ar-H), 7.44 (6H, m, Ar-H), 7.62 (4H, m, Ar-H), 7.77 (2H, m, Ar-H), 7.81 (2H, s,
Ar-H), dC (100 MHz) 40.4, 40.5, 55.2, 111.7, 121.5, 126.0, 126.2, 126.9, 127.57,
127.62, 128.1, 128.76, 128.79, 129.8, 130.0, 130.7, 131.2, 131.7, 132.4, 133.6,
144.2, 149.8, 150.1. HRMS: m/z Calcd for C39H36N2S2: 597.2393 [M+H]+. Found:
597.2389. Anal. Calcd for C39H36N2S2: C, 78.5; H, 6.1; N, 4.7. Found: C, 78.3; H,
5.9; N, 4.5. The following compounds were obtained using this protocol:
(i) 3,3-Bis(4-methoxyphenyl)-1,1-bis(2-naphthylthio)prop-2-ene (7b) [from 2-
thionaphthol and 1,1-bis(4-methoxyphenyl)prop-2-yn-1-ol (1b)] as pale
orange microcrystals from hexane/CH2Cl2, 54% (3.85 g), mp 79–80 °C, mmax
21
Ce(OTf)3 or with P2O5 in CH2Cl2, results in dithioacetal forma-
tion.18 There are apparently no accounts of the direct formation
of dithioacetals from 3,3-diarylprop-2-enals. Further investigations
of this interesting reaction of 1 with either arenethiols or aliphatic
dithiols, together with the application of the resulting dithioacetals
in traditional dithioacetal transformations22 are ongoing.
(neat) 2931, 2834, 1603, 1354, 1288, 1172, 1030, 831, 811, 742, 579, 472 cmÀ1
,
dH (400 MHz) 3.62 (3H, s, OMe), 3.69 (3H, s, OMe), 5.36 (1H, d, J = 10.8 Hz, 1-H),
6.04 (1H, d, J = 10.8 Hz, 2-H), 6.69 (4H, m, Ar-H), 6.79 (2H, m, Ar-H), 6.96 (2H,
m, Ar-H), 7.36 (4H, m, Ar-H), 7.41 (2H, m, Ar-H), 7.56 (4H, m, Ar-H), 7.65 (2H,
m, Ar-H), 7.83 (2H, s, Ar-H), dC (100 MHz) 55.7, 56.1, 114.2, 124.7, 126.1, 127.0,
127.1, 127.3, 128.1, 128.3, 128.9, 129.5, 130.7, 131.4, 131.6, 131.7, 132.7, 133.2,
134.1, 134.6, 143.5, 159.7, 160.0. HRMS: m/z Calcd for C37H30O2S2: 571.1765
[M+H]+. Found: 571.1762. Anal. Calcd for C37H30O2S2: C, 77.9; H, 5.3. Found: C,
77.5; H, 5.2.
Acknowledgements
The authors thank the University of Leeds, Rothschild Commu-
nity of Excellence for a studentship to A.J.C. and the EPSRC for ac-
cess to the National Mass Spectrometry Service (Swansea). The
Worshipful Company of Clothworkers’ of the City of London is
thanked for a millennium grant for the purchase of a Bruker
Avance NMR spectrometer.
(ii) Mixture of E- and Z-3-(4-dimethylaminophenyl)-3-(4-methoxyphenyl)-1,1-
bis(2-naphthylthio)prop-2-ene (7c,d) [from 2-thionaphthol and 1-(4-
dimethylaminophenyl)-1-(4-methoxyphenyl)prop-2-yn-1-ol (1c)] as
a pale
yellow powder from hexane/CH2Cl2, 61% (4.45 g), mp 69–70 °C, mmax (neat)
2886, 2799, 1607, 1588, 1518, 1352, 1169, 1129, 1062, 807, 739, 471 cmÀ1, dH
(400 MHz) (mixture) 2.91 (6H, s, NMe2), 2.97 (6H, s, NMe2), 3.75 (3H, s, OMe),
3.79 (3H, s, OMe), 5.29 (1H, d, J = 10.8 Hz, 1-H), 5.49 (1H, d, J = 10.8 Hz, 1-H),
5.90 (1H, d, J = 10.8 Hz, 2-H), 5.98 (1H, d, J = 10.8 Hz, 2-H), 6.52 (2H, m, Ar-H),
6.58 (2H, m, Ar-H), 6.69 (2H, m, Ar-H), 6.70 (2H, m, Ar-H), 6.84 (2H, m, Ar-H),
6.95 (6H, m, Ar-H), 7.43 (12H, m, Ar-H), 7.65 (8H, m, Ar-H), 7.76 (4H, m, Ar-H),
7.81 (4H, m, Ar-H), dC (100 MHz) (mixture) 40.36, 40.42, 55.0, 55.2, 55.7, 111.7,
113.3, 122.2, 123.2, 126.1, 126.2, 126.3, 127.56, 127.6, 127.8, 128.16, 128.2,
128.5, 129.1, 129.8, 130.2, 130.7, 130.8, 131.2, 131.3, 131.4, 131.5, 132.0,
132.45, 132.55, 133.5, 134.7, 143.3, 143.8, 149.9, 150.1, 158.9, 159.3. HRMS: m/z
Calcd for C38H33NOS2: 584.2076 [M+H]+. Found: 584.2070. Anal. Calcd for
References and notes
1. Chatterjee, P. N.; Roy, S. J. Org. Chem. 2010, 75, 4413–4423.
2. Miki, K.; Fujita, M.; Inoue, Y.; Senda, Y.; Kowada, T.; Ohe, K. J. Org. Chem. 2010,
75, 3537–3540.
3. (a) Kothandaraman, P.; Rao, W.; Foo, S. J.; Chan, P. W. H. Angew. Chem., Int. Ed.
2010, 49, 4619–4623; (b) Konno, T.; Morijasu, K.; Kinugawa, R.; Ishihara, T. Org.
Biomol. Chem. 2010, 8, 1718–1724; (c) Liu, X.-T.; Hao, L.; Lin, M.; Chen, L.; Zhan,
Z.-P. Org. Biomol. Chem. 2010, 8, 3064–3072; (d) Ji, K.-G.; Zhu, H.-T.; Yang, F.;
Shu, X.-Z.; Zhao, S.-C.; Liu, X.-Y.; Shaukat, A.; Liang, Y.-M. Chem. Eur. J. 2010, 16,
6151–6154.
4. (a) Busetto, L.; Marchetti, F.; Mazzoni, R.; Salmi, M.; Zacchini, S.; Zanotti, V.
Chem. Commun. 2010, 46, 3327–3329; (b) Chen, J.; He, G.; Sung, H. H.-Y.;
Williams, I. D.; Lin, Z.; Jia, G. Organometallics 2010, 29, 2693–2701.
5. Engel, D. A.; Dudley, G. B. Org. Biomol. Chem. 2009, 7, 4149–4158.
6. Cadierno, V.; Francos, J.; Gimeno, J. Tetrahedron Lett. 2009, 50, 4773–4776.
7. Engel, D. A.; Dudley, G. B. Org. Lett. 2006, 8, 4027–4029.
8. Gabbutt, C. D.; Heron, B. M.; Kilner, C.; Kolla, S. B. Org. Biomol. Chem. 2010, 8,
4874–4883.
9. Braun, R. U.; Ansorge, M.; Müller, T. J. J. Chem. Eur. J. 2006, 12, 9081–9094.
10. (a) Essenfeld, A. P. Eur. Pat. Appl. 1989, 302195A1 (Chem. Abstr. 1989, 111,
114890).; (b) Begley, W. J.; Rajeswaran, M.; Andrievsky, N. US. Pat. Appl. 2006,
2006025618A1 (Chem. Abstr. 2006, 144, 170799).
11. (a) Akiyama, S.; Yoshida, K.; Hayashida, M.; Nakashima, K.; Nakatsuji, S.; Iyoda,
M. Chem. Lett. 1981, 311–314; (b) Muramatsu, H.; Okumura, A.; Shibata, K.;
Matsui, M. Chem. Ber. 1994, 127, 1627–1632.
12. (a) Gabbutt, C. D.; Hepworth, J. D.; Heron, B. M.; Partington, S. M.; Thomas, D. A.
Dyes Pigments 2001, 49, 65–74; (b) Borge, J.; Cadiero, V.; Díez, J.; García-
Garrido, S. E.; Gimeno, J. Dyes Pigments 2010, 87, 209–217.
C
38H33NOS2: C, 78.2; H, 5.7; N, 2.4. Found: C, 77.9; H, 5.4; N, 2.3.
17. X-ray crystallographic data for 7a: size 0.29 Â 0.25 Â 0.16 mm; crystal
morphology pale violet fragment; T 150(2) K; wavelength 0.71073 Å [Mo K ];
crystal system triclinic, space group P1, unit cell dimensions a = 11.2303(11) Å,
a
ꢀ
a
= 80.053(5)°,
= 64.741(4)°; volume 1597.7(3) Å3; Z 2; density (calculated) 1.241 Mg/m3;
F(0 0 0) 632; data collection range
b = 11.9071(11) Å,
b = 73.146(5)°,
c = 13.8263(14)
Å,
c
absorption coefficient 0.197 mmÀ1
;
1.89 6 h 6 30.21°; index ranges À15 6 h 6 15, À16 6 k 6 16, À19 6 l 6 19;
reflections collected 45,074; independent reflections 9312 [R(int) = 0.0517];
observed reflections 7834 [I > 2
and min. transmission 0.9692 and 0.8085; refinement method full; data/
restraints/parameters 9312/0/392; goodness of fit 1.031, final indices
r(I)]; absorption correction multi-scan; max.
R
[I > 2r(I)] R1 = 0.0376, wR2 = 0.0978; R indices (all data) R1 = 0.0469,
wR2 = 0.1043; largest diff. peak and hole 0.385 and À0.232 e ÅÀ3
.
Crystallographic data (excluding structure factors) for the structure in this
paper have been deposited with the Cambridge Crystallographic Data Centre as
supplementary publication number CCDC795951. Copies of the data can be
obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2
1EZ, UK, (fax: +44-(0)1223-336033 or e-mail: deposit@ccdc.cam.ac.uk).
18. Hunter, R. Tetrahedron 1994, 50, 9377–9398.
13. Hepworth, J. D.; Heron, B. M. In Functional Dyes; Kim, S.-H., Ed.; Elsevier:
Amsterdam, 2006; pp 85–135.
19. Allenyl phenylthioethers have been isolated from simple propargyl alcohols in
two steps involving metallation and quenching with PhSCl and subsequent
addition of MeLi, see: Cutting, I.; Parsons, P. J. J. Chem. Soc., Chem. Commun.
1983, 1209–1210.
20. Ishino, Y.; Mihara, M.; Kawai, H. Synlett 2001, 1317–1319.
21. Kumar, A.; Rao, M. S.; Rao, V. K. Aust. J. Chem. 2010, 63, 135–140.
22. (a) Gröbel, B.-T.; Seebach, D. Synthesis 1977, 357–402; (b) Yus, M.; Nájera, C.;
Foubelo, F. Tetrahedron 2003, 59, 6147–6212; (c) Smith, A. B., III; Adams, C. M.
Acc. Chem. Res. 2004, 37, 365–377.
14. Hepworth, J. D.; Heron, B. M. In Progress in Heterocyclic Chemistry; Gribble, G.
W., Joule, J. A., Eds.; Elsevier: Amsterdam, 2005; Vol. 17, pp 33–62.
15. (a) Ingall, A. H. In Comprehensive Heterocyclic Chemistry; Boulton, A. J., McKillop,
A., Eds.; Pergamon Press: Oxford, 1984; Vol. 3, pp 885–942; (b) Ingall, A. H. In
Comprehensive Heterocyclic Chemistry II; McKillop, A., Ed.; Elsevier: Amsterdam,
1996; Vol. 5, pp 501–618; (c) Hepworth, J. D.; Heron, B. M. In Comprehensive
Heterocyclic Chemistry III; St, C., Black, D., Eds.; Elsevier: Amsterdam, 2008; Vol.
7, pp 931–932.
16. General method for the preparation of dithioacetals 7a–d: A stirred solution of 2-
thionaphthol (25 mmol) and the 1,1-diarylprop-2-yn-1-ol (12.5 mmol) in