Convenient Syntheses of Naturally Occurring Angular and Linear Naphthopvrans

Article abstract of DOI:10.1039/a708718g

A convenient synthesis of naturally occurring angular naphthopyrans and their 6-demethoxy derivatives is described starting from 2-acetyl-1-naphthols along with the synthesis of linear naphthopyrans from 3-acetyl-2-naphthol.

Full text of DOI:10.1039/a708718g

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3
18 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
Convenient Syntheses of Naturally Occurring
1998, 318±319$
Angular and Linear Naphthopyrans$
Madhusudan V. Paradkar,* Himanshu M. Godbole, Anup A. Ranade
and Augustine R. Joseph
Department of Chemistry, Post Graduate & Research Centre, A.G. College, Karve Road,
Pune 411 004, India
A convenient synthesis of naturally occurring angular naphthopyrans and their 6-demethoxy derivatives is described
starting from 2-acetyl-1-naphthols along with the synthesis of linear naphthopyrans from 3-acetyl-2-naphthol.
1
,2-Dimethylnaphtho[1,2-b]pyrans like mollugin, dihydro
2
lapachenole (3a), lapachenole (4a) and their 6-demethoxy
2
3
4
derivatives (3b and 4b) have been isolated from natural
5
sources. Recently 3,4-dihydronaphtho[2,3-b]pyran (7a), a
linear naphthopyran, has also been isolated from the roots
of Withania somnifera.
Although a few approaches have been reported for the
synthesis of angular naphthopyrans (3a, 3b, 4a and 4b),
surprisingly so far no attempt has been made to obtain the
linear naphthopyrans (7a, 7b and 8). The reported methods
for the synthesis of angular naphthopyrans involve (i) con-
densation of 1-naphthol with 3,3-dimethylacrylic acid or its
3
,6±9
derivatives,
ether of 1-naphthol,
with isoprene providing the dihydronaphthopyran and
iv) conversion of the corresponding benzocoumarin into
the dimethyl pyran ring system using methylmagnesium
(ii) Claisen rearrangement of the propargyl
10±12
(iii) condensation of 1-naphthol
13
(
7,14
iodide.
In connection with our interest in the synthesis of various
naturally occurring naphthopyrans and their transform-
ations into other naturally occurring and biologically active
pyranonaphthoquinones, we wanted a common method,
applicable for both angular and linear naphthopyrans. Our
approaches for the synthesis of naphthopyrans (3a, 3b, 4a,
Scheme 1 Reagents and conditions: i, acetone, pyrrolidine,
‡
C
6 6
H
; ii, Zn±Hg/HCl; iii, NaBH , MeOH; iv, H
4
3
O , 65 8C
an internal standard, IR spectra on a Perkin-Elmer FT IR 1600
spectrophotometer.
2
-Acetyl-3-hydroxynaphthalene 5.ÐA solution of the dimethyl-
amide (0.022 mol), obtained from 2-methoxy-3-naphthoyl chloride
0.027 mol) and dimethylamine (40% aqueous solution, 70 ml), in
4
naphthol (1b) was treated with acetone in the presence
b, 7b and 8) are depicted in Schemes 1 and 2. 2-Acetyl-1-
15
(
16
of pyrrolidine
to obtain 3,4-dihydro-2,2-dimethyl-4H-
dry benzene (50 ml) was treated with methylmagnesium iodide,
prepared from methyl iodide (0.05 mol) and magnesium turnings
(0.05 mol) with stirring. The reaction mixture was stirred for 4 h,
then acidi®ed using 1:1 HCl. The solvent layer, after work-up,
provided the 2-acetyl-2-methoxynaphthalene as a dark oil. This
naphtho[1,2-b]pyran-4-one (2b) in 65% yield which on
Clemmensen reduction provided 3b and on reduction
with NaBH4 followed by acid-catalysed dehydration gave
2
,2-dimethylnaphtho[1,2-b]pyran 4b. This strategy was then
(
0.02 mol) was subjected to demethylation by treating it with an
extended for the synthesis of lapachenole 4a and dihydro-
lapachenole 3a from 2-acetyl-l-hydroxy-4-methoxynaphtha-
lene 1a via the intermediacy of 2a (Scheme 1).
1
7
3
-Acetyl-2-hydroxynaphthalene 5 required for the syn-
thesis of the linear naphthopyrans 7b and 8 was obtained
as delineated below (Scheme 2). The hydroxy ketone 5
on condensation with acetone a€orded 2,2-dimethyl-4H-
naphtho[2,3-b]pyran-4-one 6 in 52% yield. The g-pyrone 6
was then converted into the 2,2-dimethylnaphtho[2,3-b]-
pyran 8 and its dihydro derivative 7b by adopting the above
conditions.
To conclude, a convenient method has been described for
the synthesis of naturally occurring angular naphthopyrans
(4a and 4b), their dihydro derivatives (3a and 3b) and the
new isomeric linear naphthopyrans (7b and 8).
Experimental
1
All melting points are uncorrected.
recorded on a JEOL FX 90 Q instrument in CDCl
H
NMR spectra were
using TMS as
3
*To receive any correspondence.
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).
Scheme 2 Reagents and conditions: i, MeMgI, C
6
H
6
; ii, AlCl
O, ethylene
3
,
CH
glycol, KOH; v, NaBH
2
Cl
2
; iii, acetone, pyrrolidine, C
, MeOH; vi, H
6 6
H
; iv, NH NH
2
2
ÁH
2
‡
4
3
O , 65 8C

View Article Online
J. CHEM. RESEARCH (S), 1998 319
intimate mixture of anhydrous aluminium chloride (0.068 mol) and
dry dichloromethane (50 ml), with vigorous stirring. The reaction
mixture was stirred for 1 h. The excess of dichloromethane was
removed under reduced pressure and the solid residue thus obtained
added portionwise to ice-cold 1:1 HCl (70 ml), when a dark solid
formed. This was ®ltered o€, dried and puri®ed by column chroma-
tography over silica gel using hexane as the eluent. The 2-acetyl-3-
hydroxynaphthalene was obtained as golden yellow ¯akes (70%
2,2-Dimethylnaphthopyrans 4a, 4b and 8.ÐTo
solution of naphthopyran-4-one (0.0022 mol) in methyl alcohol
(10 ml) was added NaBH (0.0026 mol) over a period of 20 min.
Usual work-up provided a semi-solid residue which was dissolved in
a well stirred
4
�
3
methyl alcohol (10 ml), HCl (4 mol dm , 20 ml) added and heated
at 65 8C for about 30 min. The reaction mixture was cooled, poured
into cold water and extracted with ether. Work-up of the ether
layer provided a semi-solid mass which on puri®cation by column
chromatography yielded the desired product.
17
yield); mp 110 8C (lit., 110.0±111.8 8C) (Found: C, 77.38; H, 5.40.
requires C, 77.40; H, 5.4%); ꢀ 2.5 (3 H, s, CH ), 7.0
1 H, s, H-1), 7.1±7.9 (4 H, m, H-5, H-6, H-7, H-8), 8.0 (1 H, s,
H-4), 12.6 (1 H, s, OH).
,2-Dimethylnaphthopyran-4-ones 2a, 2b and 6.ÐA solution of the
7
C
12
H O
10 2
H
3
Compound 4a. (Yield 71%); mp 56 8C (lit., 58 8C) (Found: C,
(
79.96; H, 6.70. C16
H
16
O
2
H
requires C, 79.97; H, 6.71%); d 1.55 [6 H,
s, C(CH ], 3.97 (3 H, s, OCH ), 5.68 (1 H, d, J 11, H-3), 6.43
3
3
)
2
2
(1 H, d, J 11 Hz, H-4), 6.55 (1 H, s, H-5), 7.43±7.65 (2 H, m, H-8
and H-9), 8.10±8.35 (2 H, m, H-7 and H-10).
appropriate o-acetylnaphthol (0.0162 mol), pyrrolidine (0.0080 mol)
and dry acetone (0.0240 mol) in dry benzene (30 ml) was ®rst stirred
at room temperature for about 15 min. It was then re¯uxed using a
Dean Stark separator for about 48 h, then acidi®ed with 1:1 HCl.
The organic solvent layer which separated after work-up provided a
semi-solid which on puri®cation by column chromatography using
silica gel and hexane a€orded the desired ꢁ-pyrone.
12
Compound 4b. (Yield 73%); mp 42 8C (lit., 44 8C) (Found: C,
85.66; H, 6.70. C15 14O requires C, 85.68; H, 6.71%); d 1.48 [6 H,
s, C(CH ], 5.58 (1 H, d, J 10, H-3), 6.42 (1 H, d, J 10, H-4), 7.11
H
H
3 2
)
(1 H, d, J 9, H-5), 7.33 (1 H, d, J 9, Hz, H-6), 7.34±7.51 (2 H, m,
H-8 and H-9), 7.58±7.82 (1 H, m, H-7), 8.06±8.31 (1 H, m, H-10).
Compound 8. (Yield 62%); mp 91 8C (Found: C, 85.59; H, 6.69.
7
Compound 2a. (Yield 60%); mp 124 8C (lit., 121 8C) (Found: C,
15 H 3 2
C H14O requires C, 85.68; H, 6.71%); d 1.48 [6 H, s, C(CH ) ],
7
s, C(CH ], 2.67 (2 H, s, CH
H-5), 7.13±7.40 (2 H, m, H-8 and H-9), 7.76±8.00 (2 H, m, H-7 and
H-10).
Compound 2b. (Yield 65%); Oil (lit., Oil) (Found: C, 79.60; H,
4.96; H, 6.27. C16
H
16
O
3
requires C, 74.98; H, 6.29%); d
H
1.49 [6 H,
), 3.82 (3 H, s, OCH ), 6.82 (1 H, s,
5.82 (1 H, d, J 10, H-3), 6.51 (1 H, d, J 10 Hz, H-4), 7.14 (1 H, s,
H-10), 7.20±7.40 (2 H, m, H-7 and H-8), 7.42 (1 H, s, H-5), 7.58±
7.72 (2 H, m, H-6 and H-9).
3
)
2
2
3
6
We thank Dr A. S. Inamdar, Principal, A.G. College,
Pune for providing the necessary facilities, Professor R. S.
Mali, University of Pune for useful discussions and
University of Pune for the spectral and elemental analyses.
H. M. Godbole (SRF) and A. R. Joseph (JRF) thank CSIR
for providing the ®nancial assistance.
6
.23. C15
C(CH ], 2.85 (2 H, s, CH
4 H, m, H-7, H-8, H-9, H-10), 8.33 (1 H, d, J 9, H-6 Hz).
Compound 6. (Yield 52%); mp 96 8C (Found: C, 79.61; H, 6.22.
requires C, 79.62; H, 6.24%); d 1.49 [6 H, s, C(CH ],
), 7.25±7.45 (2 H, m, H-7 and H-10), 7.45±7.60
1 H, m, H-8), 7.73 (1 H, br, J 6, H-6), 7.90 (1 H, br, J 6 Hz, H-9),
.50 (1 H, s, H-5).
,4-Dihydro-2,2-dimethylnaphthopyrans 3a, 3b.ÐWater (20 ml)
was added to a mixture of zinc powder (2.00 g) and HgCl (0.10 g).
H
14
O
2
requires C, 79.62; H, 6.24%); d
H
1.60 [6 H, s,
3
)
2
2
), 7.38 (1 H, d, J 9, H-5), 7.48±7.90
(
C
15
H
14
O
2
H
3 2
)
2
.84 (2 H, s, CH
2
(
8
3
Received, 3rd December 1997; Accepted, 9th February 1998
Paper E/7/08718G
2
The resulting slurry was shaken thoroughly for 5 min. To it was
added HCl (50%, 10 ml) and the mixture again shaken vigorously
when zinc amalgam was obtained. To this zinc amalgam was added
the ꢁ-naphthopyrone (0.0022 mol) and HCl (80%, 25 ml) and
the contents were re¯uxed for 3 h. After completion of the reaction
References
(
Monitored by TLC) the contents were extracted with diethyl
1 L. Hari, L. F. De Buyck and H. L. De Pooter, Phytochemistry,
1991, 1726.
ether. Work-up of the organic layer provided a product which
on puri®cation using column chromatography yielded the desired
dihydronaphthopyrans.
2 A. R. Burnett and R. H. Thomson, J. Chem. Soc. C, 1968, 850.
3 R. Livingstone and M. C. Whiting, J. Chem. Soc., 1955, 3631.
4 A. R. Burnett and R. H. Thomson, J. Chem. Soc. C, 1968, 854.
5 A. S. R. Anjaneyulu and Rao D. Satyanarayana, Indian J.
Chem., Sect. B, 1997, 36, 424.
6 A. S. R. Anjaneyulu, Row L. Ramachandra, Krishna C. Sri and
C. Shrinivasulu, Curr. Sci., 1968, 37, 513.
7 R. Livingstone and R. B. Watson, J. Chem. Soc., 1956, 3701.
8 L. Elhadi, M. Laurence and Z. Henri, Synth. Commun., 1993,
23, 3019.
9 V. K. Tandon, M. Vaish, S. Jain, D. S. Bhakuni and R. C.
Srimal, Indian J. Pharm. Sci., 1991, 53, 22.
10 A. S. R. Anjaneyulu and B. Isaa, J. Chem. Soc., Perkin Trans.
1, 1991, 2089.
11 J. Hlubucek, E. Ritchie and W. C. Taylor, Tetrahedron Lett.,
1969, 17, 1369.
12 B. K. Rohatgi, R. S. Gupta and R. N. Khanna, Indian J.
Chem., Sect. B, 1981, 20, 505.
14
Compound 3a. (Yield 78%); mp 73 8C (lit., 76 8C) (Found: C,
9.29; H, 7.47. C16 requires C, 79.31; H, 7.49%); d 1.43 [6 H,
s C(CH ], 1.90 (2 H, t, J 6, CH CH Ar), 2.90 (2 H, t, J 6,
CH CH Ar), 3.95 (3 H, s, OCH ), 6.50 (1 H, s, H-5), 7.30±7.60
2 H, m, H-8 and H-9), 8.05±8.25 (2 H, m, H-7 and H-10).
7
H O
18 2
H
3
)
2
2
2
2
2
3
(
12
Compound 3b. (Yield 80%); Oil (lit., Oil) (Found: C, 84.85; H,
.40. C15 16O requires C, 84.87; H, 7.60%); d 1.48 [6 H, s,
], 1.95 (2 H, t, J 6, CH CH Ar), 2.93 (2 H, t, J 6,
Ar), 7.20 (1 H, d, J 9, H-5), 7.28 (1 H, d, J 9, H-6), 7.35±
.50 (2 H, m, H-8 and H-9), 7.70±7.80 (1 H, m, H-7), 8.20±8.35
1 H, m, H-10).
,4-Dihydro-2,2-dimethylnaphtho[2,3-b]pyran 7b.ÐA mixture of
,2-dimethyl-4H-naphtho[2,3-b]pyran-4H-one 6 (0.0022 mol), hydra-
7
H
H
C(CH
CH CH
7
(
3
)
2
2
2
2
2
3
2
zine hydrate (0.5 ml) and ethylene glycol (10 ml) was re¯uxed for
5 min. To this hot solution KOH pellets (0.0053 mol) were added
1
in portions over a period of 10 min, then re¯uxed for 1 h. After
cooling, the reaction mixture was made acidic and extracted with
ether. Work-up of the organic solvent layer provided a sticky mass
which was further puri®ed by column chromatography yielding the
desired dihydronaphthopyran 7b (60% yield); mp 110 8C (Found:
13 V. K. Ahluwalia, P. K. Hira and R. S. Jolly, Indian J. Chem.,
Sect. B, 1982, 21, 961.
14 A. K. Das Gupta, R. M. Chatterje and T. P. Bhowmic,
Tetrahedron, 1969, 25, 4207.
C, 84.86; H, 7.51. C15
6 H, s, C(CH ], 1.92 (2 H, t, J 7, CH
CH CH Ar), 7.17 (1 H, s, H-5), 7.22±7.36 (2 H, m, H-7 and H-8),
.55 (1 H, s, H-10) and 7.63±7.69 (2 H, m, H-6 and H-9).
H
16O requires C, 84.87; H, 7.60%); ꢀ
H
1.39
15 I. R. Green, J. Chem. Educ., 1982, 59, 698.
16 H. J. Kabbe and A. Widdig, Angew. Chem., Int. Ed. Engl., 1982,
21, 247.
[
3
)
2
2
CH Ar), 3.01 (2 H, t, J 7,
2
2
2
7
17 I. M. Hunsberger, J. Am. Chem. Soc., 1950, 72, 5626.