Convenient phosphorus tribromide induced syntheses of substituted 1-arylmethylnaphthalenes from 1-tetralone derivatives

Article abstract of DOI:10.1016/j.tetlet.2005.06.016

A series of 1-arylmethylnaphthalenes 7a-g and 11 have been synthesized conveniently in good yields at room temperature through phosphorus tribromide induced aromatization of 1-aryl-[3,4]-dihydronaphthyl-methanols 6a-g and 10, which were obtained from 1-te

Full text of DOI:10.1016/j.tetlet.2005.06.016

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 5337–5341
Convenient phosphorus tribromide induced syntheses of
substituted 1-arylmethylnaphthalenes from 1-tetralone derivativesq
Shagufta,a Resmi Raghunandan,b Prakas R. Maulikb, and Gautam Pandaa,*
aMedicinal and Process Chemistry Division, Central Drug Research Institute, PO Box 173, Lucknow 226 001, India
bMolecular and Structural Biology Division, Central Drug Research Institute, PO Box 173, Lucknow 226 001, India
Received 4 March 2005; revised 24 May2005; accepted 2 June 2005
Available online 23 June 2005
Abstract—A series of 1-arylmethylnaphthalenes 7a–g and 11 have been synthesized conveniently in good yields at room temperature
through phosphorus tribromide induced aromatization of 1-aryl-[3,4]-dihydronaphthyl-methanols 6a–g and 10, which were
obtained from 1-tetralone derivatives.
ꢀ 2005 Elsevier Ltd. All rights reserved.
Arylnaphthylmethane derivatives are important build-
ing blocks in organic synthesis. These compounds con-
stitute the basic skeleton of manybiologically
important natural products and pharmaceuticals.1
Naphthoyl and naphthylmethyl substituted D8-tetra-
hydrocannabinol analogues 1 and 2 have cannabimi-
metic activity.2 Naphthyl acetamides 3 are used for
inhibiting secreted phospholipase A2 (sPLA2)-mediated
release of fattyacids and in the treatment of conditions
such as septic shock, adult respiratorydistress sny-
drome, pancreatitis, trauma, bronchial asthma, allergic
rhinitis and rheumatoid arthritis (Fig. 1).3
ing substituted 1-arylmethylnaphthalenes, which are also
a class of diarylmethanes. These classes of compounds
have been prepared previouslyusing different methods
such as palladium catalyzed cross coupling between phe-
nyl or naphthyl boronic acids and benzylic bromides,5
copper catalyzed reactions of arylmagnesium derivatives
with benzyl iodides,6 nickel catalyzed cross coupling of
arylphosphates with Grignard and organoaluminium
reagents,7 acid catalyzed rearrangement of cyclobuta-
nols,8 reduction of arylnaphthyl carbinols9 or reduction
of arylnaphthylketones.10 These procedures describe
syntheses of arylmethylnaphthalenes through functional
group transformation or cross coupling reactions
between two aromatic moieties. Additionally1-substituted
naphthalenes can be prepared from a-tetralone in acidic
In continuation of our earlier work on aryl substituted
methane derivatives,4 we became interested in synthesiz-
O
X= O, CH
2
1
2
O
NH2
R1
R , R = H
3
O
R3
R
= H, O(CH ) Y, O(CHMe) Y,
2 n n
OH
OH
O(CHCH CH Ph) Y
2
2
n
Y=CO2H, PO3H2, SO3H
n=2-4
O
X
R2
1
2
3
Figure 1. Structures of some biologically important arylmethylnaphthalene derivatives.
Keywords: Phosphorus tribromide; 1-Arylmethylnaphthalenes.
q CDRI Communication No. 6710.
*
Corresponding author. Tel.: +91 5222364635; fax: +91 5222223938; e-mail addresses: bapi.rm@yahoo.com; gautam_panda@lycos.com
For crystallographic queries.
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.06.016

5338
Shagufta et al. / Tetrahedron Letters 46 (2005) 5337–5341
or basic medium bya xanthate mediated addition–cycli-
zation sequence11 and bromination of 1,1-dibenzyl tetra-
It was anticipated that transforming the hydroxyl func-
tionalityin allyl alcohols 6a–g and 10 into a leaving
group might enforce aromatization through elimination
of the leaving group from the a0-position of the dihydro-
naphthalene ring. Attempts to convert the hydroxyl
functionalityinto a p-toluenesulfonyl group with p-TsCl
were unsuccessful. Instead, PBr3 was reacted with 6a–g
and 10 to transform the hydroxyl functionality into an
–OPBr2 group, which has been reported to effect aroma-
tization13 providing access to arylmethylnaphthalenes.
To our delight, when allyl alcohols 6a–g and 10 were
reacted with PBr3 at 0 ꢁC, the reaction proceeded
smoothly and efficiently, providing good yields of
1-arylmethylnaphthalenes 7a–g and 11 (Table 1). The
reaction was veryfast and complete within 5–10 min
and did not require anyheating or drastic conditions.
lin derivatives.12 We herein report
a new and
straightforward synthetic approach towards 1-arylmeth-
ylnaphthalene and its derivatives through facile aromati-
zation of 1-aryl-[3,4]-dihydronaphthyl-methanols.
Treatment of 6-methoxy-1-tetralone 4 and 1-tetralone 8
with PBr3 in drybenzene at 80 ꢁC for 2–3 h furnished
bromo derivatives 5 (60%) and 9 (50%), respectively.
The lithio derivatives of 5 and 9 were synthesized by
treatment with n-BuLi at ꢀ78 ꢁC for 1 h in dryTHF.
The anion thus generated was reacted with several alde-
hydes (R2CHO, R2 = aryl and heteroaryl) to furnish a
series of 1-aryl-3,4-dihydronaphthyl-methanols 6a–g
and 10 in 50–60% yields (Table 1).
Table 1. Synthesis of 1-arylmethylnaphthalenes 7a–g and 11
HO
R2
PBr3 (1.5 eq.)
R2
Br
O
n-BuLi (1.1 eq.)
PBr3 (1.5 eq.)
Benzene,
R2CHO (1 eq.)
R1
R1
R1
R1
-78 oC, 1-2 h
80 oC, 2-3 h,
50-60 %
1
1
1
1
1
4, R =OCH
8, R =H
5, R =OCH
9, R =H
6a-g, R =OCH
3
3
7a-g, R =OCH
3
3
1
1
1
11, R =H
10, R =H
EntrySubstrate
R
2CHO
Carbinol yield (%)
Reaction conditions
{PBr3 (1.5 equiv)
in drybenzene}
1-Arylmethylnaphthalene
yield (%)
OCH3
OCH3
CHO
Br
HO
a
0 ꢁC, 5 min
H3CO
5
OCH3
CHO
H3CO
H3CO
H3CO
6a (60%)
7a (65%)
Br
HO
b
0 ꢁC, 8 min
H3CO
5
H3CO
7b (63%)
7c (49%)
6b (55%)
Br
HO
O
S
O
S
c
0 ꢁC, 6 min
CHO
O
H3CO
H3CO
H3CO
H3CO
5
6c (58%)
Br
HO
d
0 ꢁC, 6 min
CHO
S
H3CO
H3CO
5
6d (50%)
7d (42%)
H3CO
OCH3
H3CO
HO
OCH3
CHO
Br
OCH3
e
0 ꢁC, 5 min
H3CO
5
OCH3
H3CO
H3CO
6e (53%)
7e (67%)

Shagufta et al. / Tetrahedron Letters 46 (2005) 5337–5341
5339
Table 1 (continued)
EntrySubstrate
R
2CHO
Carbinol yield (%)
Reaction conditions
{PBr3 (1.5 equiv)
in drybenzene}
1-Arylmethylnaphthalene
yield (%)
Br
CHO
HO
f
0 ꢁC, 5 min
H3CO
5
5
H3CO
H3CO
6f (56%)
7f (61%)
OCH3
OCH3
OCH3
OCH3
CHO
Br
HO
OCH3
OCH3
g
0 ꢁC, 5 min
H3CO
OCH3
OCH3
H3CO
H3CO
H3CO
7g (55%)
6g (53%)
OCH3
OCH3
CHO
Br
HO
h
0 ꢁC, 5 min
9
OCH3
10 (60%)
11 (59%)
From close inspection of structures of 6a–g and 10, it
was clear that the substituent R2 could be an aryl or het-
eroaryl group. The reaction was independent of the sub-
stituent R1 on the dihydronaphthalene ring of 6a–g and
10. Dehydrogenation of hydronaphthalenes is well
known and is frequentlythe last step in the synthesis
of aromatic hydrocarbons and their derivatives. The
use of Pd/C, sulfur, selenium, DDQ and chloranil to
effect aromatization is well established.14 A catalyst,
The structure of one of the 1-arylmethylnaphthalenes 7a
was confirmed through single crystal X-ray diffraction
analysis.17 Figure 2 shows the crystal structure and its
conformation with the atomic numbering scheme used.
The molecule contains a planar naphthalene with a
methoxygroup substituted at C3 and a 4-methoxy
hydrogen acceptor, acidic conditions, high temperatures
15,16
and long reaction times are usuallyrequired.
In
these procedures, aromatization occurred through elimi-
nation of hydrogen or the leaving group from the di- or
tetrahydro aromatic rings. Under our conditions, elimi-
nation of the leaving group from the a0-position of the
ring B enforced aromatization furnishing 7a–g and 11.
The reaction can be thought to proceed via the forma-
tion of an intermediate 12, formed through the reaction
of allyl alcohols 6a–g and 10 with PBr3 followed byelimi-
nation of HBr, the intermediate 12 rearranging into the
reactive quinoid 13. Finally, 13 transforms into the more
stable conjugated aromatic species 7a–g or 11 (Scheme
1).
Figure 2. ORTEP diagram showing the molecular structure of 7a.
R2
H
R2
PBr3
-HBr
H
R2
Br2PO
A
R2
HO
H
H
H
B
A
A
A
B
B
B
R1
R1
R1
R1
H
H
6a-g, R1 =OCH3
7a-g, R1 =OCH3
11, R1 =H
12
10, R1 =H
13
Scheme 1. Possible reaction mechanism.

5340
Shagufta et al. / Tetrahedron Letters 46 (2005) 5337–5341
10. Gribble, G. W.; Kelly, W. J.; Emery, S. E. Synthesis 1978,
10, 763–765.
11. Vargas, A. C.; Martin, I. P.; Sire, B. Q.; Zard, S. Z. Org.
Biomol. Chem. 2004, 2, 3018–3025.
12. Miller, B.; Shi, X. Tetrahedron 1992, 48, 4919–4928.
13. Nampalli, S.; Binde, R. S.; Nakai, H. Synth. Commun.
1992, 22, 1165–1167.
14. (a) Phillips, D. D.; Chatterjee, D. N. J. Am. Chem. Soc.
1958, 80, 4360–4364; (b) Fieser, L. F.; Hershberg, E. B.;
Long, L.; Newman, M. S. J. Am. Chem. Soc. 1937, 59,
475–478; (c) Buu-Noi, N. P.; Lavit, D.; Lamy, J. J. Chem.
Soc, Perkin Trans. 2 1959, 1845–1849; (d) Wolthuis, E.
J. Org. Chem. 1961, 26, 2215–2220; (e) Hertz, W.; Caple,
G. J. Org. Chem. 1964, 29, 1691–1699; (f) Harvey, R. G.;
Fu, P. P.; Cortez, C.; Pataki, J. Tetrahedron Lett. 1977, 40,
3533–3536.
benzyl group at C9. The naphthalene and methoxy
group at C3 are nearlyplanar while the twist angle
between the least-squares mean plane of the 4-methoxy
benzyl group and naphthalene ring is 79.9(1)ꢁ.
In summary, we have demonstrated that 1-arylmethyl-
naphthalenes 7a–g and 11 can convenientlybe synthe-
sized from 1-tetralone and its derivatives in good
yields. The procedure involves readily available inexpen-
sive starting materials and a rare example of aromatiza-
tion under extremelymild conditions (0 ꢁC, 5–8 min).
The procedure can be applied to combinatorial synthesis
of various 1-arylmethylnaphthalenes and work towards
this direction is underway.
15. Fu, P. P.; Harvey, R. G. Chem. Rev. 1978, 78, 317.
16. Jha, A.; Padmanilayam, M. P.; Dimmock, J. Synthesis
2002, 4, 463–465.
Acknowledgements
17. Crystal data for 7a: C19H18O2, M = 278.33, Monoclinic,
˚
This research project was supported bythe Department
of Science and Technology(SR/FTP/CSA-05/2002),
New Delhi, India. Shagufta and Resmi Raghunandan
thank the CSIR for providing fellowships.
P21/n, a = 9.805(2), b = 5.482 (1), c = 27.984(4)ꢀA1,
3
˚
b = 91.74(1)ꢁ, V = 1503.5(5) A , Z = 4, Dc = 1.230 g cm
,
l(Mo-Ka) = 0.078 mmꢀ1, F(000) = 592, colourless crys-
tal, size: 0.6 · 0.35 · 0.4 mm, 3857 reflections measured
(1071 unique), Rw = 0.2002 for all data, R = 0.0891
wR2 = 0.2405 for 2663 on F values of reflections with
I > 2r(I), S = 1.037 for all data and 193 parameters. Unit
cell determination and intensitydata collection (2 h = 50ꢁ)
were performed on a Bruker P4 diffractometer at 293(2) K.
The structure was solved bydirect methods and refine-
ments were made byfull-matrix least-squares methods on
F2. Programs: XSCANS [(Siemens Analytical X-ray
Instrument Inc.: Madision, WI, USA, 1996) was used
for data collection and data processing], SHELXTL-NT
[(Bruker Axs Inc.: Madison, WI, USA, 1997) was used for
structure determination, refinements and molecular graph-
ics]. Further details of the crystal structure investigation
can be obtained from the Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge, CB21EZ, UK
(CCDC deposition No: 272578).
Supplementary data
Supplementarydata associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.2005.
06.016.
References and notes
1. (a) Gopalsamy, A.; Lim, K.; Ellingboe, J. W.; Mitsner, B.;
Nikitenko, A.; Upeslacis, J.; Mansour, T. S.; Olson, M.
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62, 721–725; (c) Meyers, A. I.; Willemsen, J. J. Tetra-
hedron Lett. 1996, 37, 791–792.
Typical procedure for 7a–g and 11: To a solution of
carbinol 6a–g or 10 {0.100 g (1 equiv)} in drybenzene
(5 mL) at 0 ꢁC was added PBr3 (1.5 equiv) and the mixture
was stirred at room temperature. After completion of
reaction, the mixture was poured into ice-cold water and
extracted with ethyl acetate. Column chromatography of
the crude product over silica gel (ethyl acetate/hexane)
furnished compounds 7a–g and 11.
2. Papahatjis, P.; Kourouli, T.; Makriyanis, A. J. Heterocycl.
Chem. 1996, 33, 559–562.
3. (a) Goodson, T., Jr.; Harper, R. W.; Herson, D. K. Chem.
Abstr. 1997, 127, 108778q; (b) Goodson, T., Jr.; Harper,
R. W.; Herson, D. K. Chem. Abstr. 1997, 127, 108779r.
4. (a) Panda, G.; Shagufta; Mishra, J. K.; Chaturvedi, V.;
Srivastava, A. K.; Srivastava, R.; Srivastava, B. S. Bioorg.
Med. Chem. 2004, 12, 5269–5276; (b) Panda, G.; Mishra,
J. K.; Sinha, S.; Gaikwad, A. K.; Srivastava, A. K.;
Srivastava, R.; Srivastava, B. S. Arkivoc 2005, 2, 29–45; (c)
Das, S. K.; Shagufta; Panda, G. Tetrahedron Lett. 2005,
46, 3097–3102.
5. (a) Nobre, S. M.; Monteiro, A. L. Tetrahedron Lett. 2004,
45, 8225–8228; (b) Chowdhury, S.; Georghiou, P. E.
Tetrahedron Lett. 1999, 40, 7599–7603.
6. Ku, Y. Y.; Patel, R. R.; Sawick, D. P. Tetrahedron Lett.
1996, 37, 1949–1952.
Selected spectral data:
2-(6-Methoxynaphthalen-1-ylmethyl)furan 7c: IR (Neat):
2928, 2365, 1220, 1025, 769 cmꢀ1 1H NMR (200 MHz,
.
CDCl3): d 3.90 (s, 3H, OCH3), 4.36 (s, 2H, ArCH2), 5.89
(d, 1H, J = 2.9 Hz, furyl H), 6.25 (dd, 1H, J1 = 3.0 Hz,
J2 = 1.9 Hz, furyl H), 7.15–7.24 (m, 3H, ArH), 7.32–7.41
(m, 2H, furyl H, ArH), 7.65 (d, 1H, J = 8.1, ArH), 7.9 (d,
1H, J = 9.4, ArH); 13C NMR (50 MHz, CDCl3): d 34.7,
56.0, 105.7, 110.4, 118.2, 124.1, 125.1, 125.3, 126.9, 128.4,
133.9, 134.6, 141.5, 152.5, 157.4. MS (FAB): m/z (%) 238
(100), [M+], 171 (55), [M+ꢀC4H3O]. Anal. C16H14O2;
Calcd: C, 80.65; H, 5.92. Found: C, 80.92; H, 5.99.
7. Hayashi, T.; Katsuro, Y.; Okamoto, Y.; Kumada, M.
Tetrahedron Lett. 1981, 22, 4449–4452.
1-(2,4-Dimethoxybenzyl)-6-methoxynaphthalene 7e: IR
(KBr): 3009, 3938, 1611, 1506, 1260, 1213, 1156, 1041,
8. (a) Ruff, E. L.; Hopkinson, A. C.; Moghaddam, H. K.;
Gupta, B.; Katz, M. Can. J. Chem. 1982, 60, 154–159; (b)
Ruff, E. L.; Hopkinson, A. C.; Moghaddam, H. K.;
Duperrouzel, P.; Gupta, B.; Katz, M. Tetrahedron Lett.
1981, 22, 4917–4920.
758 cmꢀ1 1H NMR (200 MHz, CDCl3): d 3.75 (s, 3H,
.
OCH3), 3.84 (s, 3H, OCH3), 3.90 (s, 3H, OCH3), 4.29 (s,
2H, ArCH2Ar), 6.29 (dd, 1H, J1 = 2.4 Hz, J2 = 8.2 Hz,
ArH), 6.50 (d, 1H, J = 2.2 Hz, ArH), 6.70 (d, 1H,
J = 8.4 Hz, ArH), 7.15–7.10 (m, 3H, ArH), 7.35 (t, 1H,
J = 7 Hz, ArH), 7.62 (d, 1H, J = 8.2 Hz, ArH), 7.88 (d,
1H, J = 9 Hz, ArH); 13C NMR (50 MHz, CDCl3): d 32.3,
9. Gribble, G. W.; Leese, R. M.; Evans, B. E. Synthesis 1977,
3, 172–176.

Shagufta et al. / Tetrahedron Letters 46 (2005) 5337–5341
5341
55.7, 55.8, 98.7, 104.3, 106.9, 118.7, 121.8, 125.3, 126.1,
126.4, 126.6, 128.2, 130.6, 135.5, 137.4, 157.6, 158.3, 159.7;
MS (FAB): m/z (%) 308 (100), [M+], 171 (70),
[M+ꢀ(OCH3)2C6H3], Anal. C20H20O3; Calcd: C, 77.90;
H, 6.54. Found: C, 77.95; H, 6.58.
1-(4-Methoxybenzyl)naphthalene 11: IR (KBr): 3435,
.
1597, 1507, 1244, 1029, 796 cmꢀ1 1H NMR (200 MHz,
CDCl3): d 3.76 (s, 3H, OCH3), 4.38 (s, 2H, ArCH2Ar),
6.79 (d, 2H, J = 8.6 Hz, ArH), 7.11 (d, 2H, J = 8.54, ArH),
7.26 (d, 1H, J = 6.6 Hz, ArH), 7.47–7.41 (m, 3H, ArH),
7.74 (d, 1H, J = 8.2 Hz, ArH), 7.84 (m, 1H, ArH), 7.99 (m,
1H, ArH); 13C NMR (50 MHz, CDCl3): d 38.5, 55.6,
114.3, 124.7, 125.3, 126.3, 127.5, 130.1, 132.5, 133.1, 134.3,
137.5, 158.3; MS (FAB): m/z (%) 248 (100), [M+], 141 (80),
[M+ꢀOCH3C6H4] Anal. C18H16O; Calcd: C, 87.06; H,
6.49. Found: C, 87.10; H, 6.45.