A simple and efficient method for the preparation of 1-benzyloxy-5- hydroxynaphthalene

Article abstract of DOI:10.1055/s-1999-2610

1,5-Dihydroxynaphthalene is a versatile π-electron rich aromatic ring system which has been employed widely for the construction of mechanically- interlocked molecular compounds and supramolecular complexes. A much-needed procedure for its transformation into 1-benzyloxy-5-hydroxynaphthalene has been developed. It involves (i) bisacetylation of 1,5-dihydroxynaphthalene, (ii) reductive removal of one of the two acetyl groups, (iii) benzylation, and (iv) cleavage of the remaining acetyl group.

Full text of DOI:10.1055/s-1999-2610

330
LETTER
A Simple and Efficient Method for the Preparation of 1-Benzyloxy-5-
hydroxynaphthalene
Jan Becher,a Owen A. Matthews,b Mogens B. Nielsen,a,c Françisco M. Raymo,c J. Fraser Stoddartc*
aDepartment of Chemistry, Odense University, Campusvej 55, DK–5230 Odense M, Denmark
bSchool of Chemistry, University of Birmingham, Edgbaston, B15 2TT Birmingham, UK
cDepartment of Chemistry and Biochemistry, University of California, Los Angeles, 405 Hilgard Avenue, Los Angeles,
CA 90095–1569, USA
Fax 1 310 206 1843; E-mail stoddart@chem.ucla.edu
Received 4 January 1998
Abstract: 1,5-Dihydroxynaphthalene is a versatile p-electron rich
aromatic ring system which has been employed widely for the con-
struction of mechanically-interlocked molecular compounds and
supramolecular complexes. A much-needed procedure for its trans-
formation into 1-benzyloxy-5-hydroxynaphthalene has been devel-
oped. It involves (i) bisacetylation of 1,5-dihydroxynaphthalene,
(ii) reductive removal of one of the two acetyl groups, (iii) benzyla-
tion, and (iv) cleavage of the remaining acetyl group.
Key words: 1,5-dihydroxynaphthalene, protection, deprotection
Recently, a number of template-directed synthetic proce-
dures affording 1,5-dioxynaphthalene-containing cat-
enanes,1
double
helices,2
molecular
knots,3
pseudorotaxanes,4 rotaxanes,5 and self-complexing
macrocycles6 have been developed. These procedures all
involve the syntheses of appropriate 1,5-dioxynaphtha-
lene-based polyethers which are employed subsequently
as templates for the construction of molecular assemblies
or supramolecular arrays. Often, the syntheses of these
templates require the monoprotection of 1,5-dihydroxy-
naphthalene. The method of choice3,4a,7 for the monopro-
tection has been the direct monoalkylation of 1,5-dihy-
droxynaphthalene with PhCH2Br in the presence of
K2CO3. However, this procedure is not easy to reproduce7
or to carry out on a reasonable scale7 and, as a result, al-
ternative and low yielding routes, avoiding the monopro-
tection of 1,5-dihydroxynaphthalene, have been devised
and used3,7 for large scale syntheses of templates. Here,
we report a simple and efficient four-step procedure
(Scheme) for the synthesis of 1-benzyloxy-5-hydroxy-
naphthalene.
Acetylation of 1 with Ac2O in C5H5N was carried out8 us-
ing a modification of a literature procedure.9 The resulting
diacetate 2 can be isolated8 in large quantities (ca. 30 g)
and in very high yield (97%). The reductive removal of
one of the two acetyl groups was achieved10 by treating 2
with NaBH4 in a mixture of EtOH and PhMe (1:3) to
afford11 the monoacetate 3 in good yield (59%). The free
hydroxyl group of 3 was alkylated with PhCH2Br in the
presence of K2CO3 in MeCN to afford12 4 in a yield of
86%. The remaining acetyl group of 4 can then be re-
moved, either by reduction, or by hydrolysis. Treating 4
with NaBH4 in a mixture of EtOH and PhMe (1:3) gave13
1-benzyloxy-5-hydroxynaphthalene (5) in a 72% yield.
Scheme
Similarly, reaction of 4 with KOH in a mixture of H2O and
dioxane (2:3) afforded14 the benzyl ether 5 in a quantita-
tive yield. In both instances, the benzyl group ‘survived’
the reaction conditions required for the deprotection.
1-Benzyloxy-5-hydroxynaphthalene can be now prepared
in an overall yield of 49% starting from the commercially
available 1,5-dihydroxynaphthalene. Thus, this procedure
offers the possibility of preparing rapidly and efficiently
large quantities of such an indispensable intermediate for
the construction of 1,5-dihydroxynaphthalene-based
polyethers, both acyclic and cyclic.
References and Notes
(1) For recent examples of catenanes based on macrocyclic com-
ponents containing 1,5-dioxynaphthalene ring systems, see:
a) Asakawa, M.; Ashton, P. R.; Balzani, V.; Credi, A.;
Hamers, C.; Mattersteig, G.; Montalti, M.; Shipway, A. N.;
Spencer, N.; Stoddart, J. F.; Tolley, M. S.; Venturi, M.; White,
A. J. P.; Williams, D. J. Angew. Chem. Int. Ed., 1998, 37, 333;
b) Ashton, P. R.; Boyd, S. E.; Menzer, S.; Pasini, D.; Raymo,
F. M.; Spencer N.; Stoddart, J. F.; White, A. J. P.; Williams,
Synlett 1999, No. 3, 330–332 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
A Simple and Efficient Method for the Preparation of 1-Benzyloxy-5-hydroxynaphthalene
331
D. J.; Wyatt, P. G. Chem. Eur. J., 1998, 4, 299; c) Ballardini,
(8) A solution of 1 (20 g) in Ac2O (100 mL) and C5H5N (110 mL)
was heated for 7 h at 100°C under an atmosphere of N2. After
cooling down to room temperature, the remaining Ac2O was
destroyed by adding carefully H2O. The resulting mixture was
poured into H2O (1 L) and stirred for 20 min. The precipitate
was filtered off, washed with H2O, air dried, and passed
through a plug of SiO2 using CH2Cl2/Me2CO (99:1) as eluant
to afford 2 (29.5 g, 97%) as a yellow solid. M.p. = 158–
159°C. EIMS: m/z (%) = 244 (53) [M]+, 202 (100), 160 (49),
131 (10). 1H–NMR (CDCl3): δ = 2.47 (6H, s), 7.30 (2H, dd,
J = 7 and 1 Hz), 7.51 (2H, dd, J = 8 and 7 Hz), 7.79 (2H, dd,
J = 8 and 1 Hz). 13C–NMR (CDCl3): δ = 21.0, 118.8, 119.3,
126.0, 128.1, 129.0, 146.7, 169.3. Anal. calcd for C14H12O4:
C = 68.85, H = 4.95; found: C = 68.67, H = 5.10.
R.; Balzani, V., Gandolfi, M. T.; Gillard R. E.; Stoddart, J. F.;
Tabellini, E. Chem. Eur. J., 1998, 4, 449; d) Amabilino, D. B.;
Ashton, P. R.; Stoddart, J. F. White, A. J. P.; Williams, D. J.
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4, 590; f) D. B. Amabilino, P. R. Ashton, S. E. Boyd, J. Y. Lee,
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(11) A mixture of 2 (5.0 g), NaBH4 (0.38 g), EtOH (25 mL), and
PhMe (75 mL) was stirred for 6 h at room temperature under
an atmosphere of N2. The solution was diluted with Et2O (200
mL) and washed with H2O (2 × 100 mL). The organic layer
was dried (MgSO4) and concentrated under reduced pressure.
The residue was purified by column chromatography (SiO2,
hexane/ CH2Cl2/Me2CO 15:4:1) to yield 3 (2.46 g, 59%) as a
white solid. M. p. = 145–147.5°C. EIMS: m/z (%) = 202 (75)
[M]+, 160 (100), 131 (60), 103 (11). 1H–NMR (CDCl3): δ =
2.47 (3H, s), 5.53 (1H, s), 6.74 (1H, dd, J = 8 and 1 Hz), 7.24–
7.31 (2H, m), 7.39–7.46 (2H, m), 8.04 (1H, dd, J = 9 and 1
Hz). 13C–NMR (CDCl3): δ = 21.0, 109.2, 113.6, 118.7, 120.0,
124.6, 125.8, 126.6, 128.0, 146.4, 151.6, 169.9. Anal. calcd
for C12H10O3: C = 71.28, H = 4.98; found: C = 71.30, H = 5.04.
(12) A degassed solution of 3 (1.0 g) in MeCN (20 mL) was added
slowly to a degassed suspension of PhCH2Br (1.0 g), K2CO3
(0.8 g), and 18-crown-6 (ca. 50 mg) in MeCN (20 mL) man-
tained at 50°C under an atmosphere of N2. The mixture was
heated for a further 3 h at 50°C and, after cooling down to
room temperature, was concentrated under reduced pressure.
The residue was partitioned between H2O and Et2O (contain-
ing a small amount of Me2CO). The organic layer was dried
(MgSO4) and concentrated under reduced pressure to afford 4
(1.3 g, 86%), after washing with hexane, as a white solid. M.p.
= 131–132°C. EIMS: m/z (%) = 292 (38) [M]+, 250 (32), 159
(9), 131 (5), 91 (100). 1H–NMR (CDCl3): δ = 2.46 (3H, s),
5.26 (2H, s), 6.92 (1H, d, J = 7 Hz), 7.27 (1H, dd, J = 8 and 1
Hz), 7.36–7.54 (8H, m), 8.26 (1H, dd, J = 9 and 1 Hz). 13C–
NMR (CDCl3): δ = 21.0, 70.2, 105.8, 113.6, 118.8, 120.4,
124.7, 126.6, 127.1, 127.4, 127.9, 128.0, 128.6, 136.8, 146.4,
154.6, 169.5. Anal. calcd for C19H16O3: C = 78.06, H = 5.52;
found: C = 78.06, H = 5.50.
(13) A mixture of 4 (4.53 g), NaBH4 (0.68 g), EtOH (25 mL), and
PhMe (75 mL) was stirred for 6 h at room temperature under
an atmosphere of N2. The solution was diluted with Et2O (200
mL) and washed with H2O (2 × 200 mL). The organic layer
was dried (MgSO4) and concentrated under reduced pressure.
The residue was purified by column chromatography [SiO2,
(i) CH2Cl2, (ii) Me2CO] to yield 5 (2.79 g, 72%) as a white so-
lid. M. p. = 135.5°C. EIMS: m/z (%) = 250 (57) [M]+, 159
(18), 131 (24), 103 (11), 91 (100). 1H–NMR (CDCl3): δ =
5.21 (1H, s), 5.26 (2H, s), 6.86 (1H, dd, J = 8 and 1 Hz), 6.93
(1H, d, J = 8 Hz), 7.29–7.45 (5H, m), 7.53–7.55 (2H, m), 7.78
(1H, d, J = 8 Hz), 7.96 (1H, dd, J = 9 and 1 Hz). 13C–NMR
(CDCl3): δ = 70.1, 105.9, 109.5, 113.9, 115.0, 125.2, 125.2,
125.4, 127.1, 127.3, 127.9, 128.6, 137.1, 151.1, 154.4. Anal.
calcd for C17H14O2: C = 81.58, H = 5.64; found: C = 81.40, H
= 5.82.
(3) Ashton, P. R.; Matthews, O. A.; Menzer, S.; Raymo, F. M.;
Spencer, N.; Stoddart, J. F.; Williams, D. J. Liebigs Ann./Re-
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M. Z.; Spencer, N.; Stoddart, J. F.; Williams, D. J. Tetrahe-
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332
J. Becher et al.
LETTER
(14) A solution of KOH (2.00 g) in H2O (50 mL) was added to a
degassed solution of 4 (1.95 g) in dioxane (50 mL) and the
mixture was heated for 2 h under reflux and an atmosphere of
N2. After cooling down to room temperature, the solution was
diluted with H2O (300 mL) and extracted with CH2Cl2 (2 ×
300 mL). The combined organic phases were dried (MgSO4)
and the solvent was removed under reduced pressure to afford
5 (1.67 g, 100%) as a white solid.
Synlett 1999, No. 3, 330–332 ISSN 0936-5214 © Thieme Stuttgart · New York