A streamlined synthesis for 2,7-diformyl-1,8-naphthalenediol

Article abstract of DOI:10.1055/s-2004-817755

2,7-Diformyl-1,8-naphthalenediol, an extension of the numerously used precursor 2,6-diformylphenol for the synthesis of various ligand systems, has been synthesized by a double Directed ortho Metalation reaction.

Full text of DOI:10.1055/s-2004-817755

LETTER
735
A Streamlined Synthesis for 2,7-Diformyl-1,8-naphthalenediol
S
ynthesis of 2,7
h
-Diformyl-1
o
,8-naphthalen
r
ediol sten Glaser,* Ioannis Liratzis
Institut für Anorganische und Analytische Chemie, Westfälische Wilhelms-Universität Münster, Wilhelm-Klemm-Str. 8, 48149 Münster,
Germany
Fax +49(251)8333108; E-mail: tglaser@uni-muenster.de
Received 8 December 2003
prevent polymerization. Nevertheless, we have not been
Abstract: 2,7-Diformyl-1,8-naphthalenediol, an extension of the
able to isolate 2,7-bis(hydroxymethyl)-1,8-naphthalene-
numerously used precursor 2,6-diformylphenol for the synthesis of
diol by the reaction of the diol 1 with formaldehyde. Even
various ligand systems, has been synthesized by a double Directed
the application of advanced synthetic methodologies via a
Mannich reaction,4 via a Vilsmeier reaction,5 via a Duff
reaction,6 or using benzene boronic acid7 or SnCl4 as
catalyst8 have not been successful. This may be due to a
combined effect of the lack of protection of the positions
para to the hydroxy groups in 1 and the increased reactiv-
ity of naphthalene derivatives as compared to the analo-
gous benzene derivatives. Therefore, we decided to utilize
a Directed ortho Metalation (DoM) reaction9 with meth-
oxymethoxy (MOM)10 as ortho directing metalation
group (DMG).
ortho Metalation reaction.
Key words: aldehydes, lithiation, Directed ortho Metalation,
formylation
In 1970, Robson introduced the symmetrical dialdehyde
2,6-diformylphenol I and its substituted analogues as
precursors for the synthesis of dinucleating ligands (com-
partmental ligands, Robson type ligands).1 Since then,
numerous studies have employed these ligand systems,
either in acyclic or macrocyclic versions. The synthesis of
homo- as well as hetero-dinuclear transition metal com-
plexes allowed detailed investigations of their magne-
tochemical and electrochemical properties. These studies
provided important insight into the molecular and elec-
tronic structure of dinuclear metallo-proteins and into the
cooperativity of such sites in catalysis.2
The introduction of the DMG was readily performed by
the reaction of 1 with NaH and chloromethyl methyl ether
(MOMCl) in DMF–Et2O to give 1,8-bis(meth-
oxymethoxy)naphthalene 2 in 88% yield (Scheme 1). Our
synthetic protocol is improved in comparison to a pub-
lished procedure11 with respect to an increased yield (88%
compared to 56%) and to a decreased amount of the car-
cinogenic MOMCl (2.5 equiv compared to 6.0 equiv). Re-
crystallization from hot n-hexane yielded colorless
crystals. The molecular structure of 2 was established by
single-crystal X-ray diffraction (Figure 2).12 Both MOM
groups are on the same side of the naphthalene ring plane
indicating the absence of steric hindrance between two
MOM substituents in 1,8 position. In this respect, it is
interesting to note that we were not able to isolate the
bis-tetrahydropyranyl (THP) ether derivative of 1, which
we initially intended to use for the DoM reaction. We
could only isolate the mono-THP derivative of 1. The
formation of THP ethers is an equilibrium reaction, which
can be easily manipulated by electronic and steric factors.
Although there seems to be no steric hindrance for two
MOM groups in 1,8 position of 1, there has to be at
least some steric stress for two THP ether rings that is
strong enough to shift the equilibrium to the mono-THP
derivative.
Figure 1
Herein, we report a streamlined synthesis for the previ-
ously unknown dialdehyde 2,7-diformyl-1,8-naphthal-
enediol II, which is an extension of the dialdehyde I
(Figure 1). The naphthalene-extended precursor molecule
has been designed for the development of novel trinucle-
ating ligand systems.
In order to prepare II, we have chosen 1,8-naphthalene-
diol (1) as starting material. Our first attempts to introduce
the 2,7-functionality in 1 involved the bis-ortho-hy-
droxymethylation in analogy to the synthesis of 2,6-
bis(hydroxymethyl)phenol derivatives.3 However, the re-
action of phenols with formaldehyde is the established
procedure to prepare insoluble phenol-formaldehyde res-
ins. Sophisticated protocols have been established espe-
cially in the case of 4-substituted phenol derivatives to
The key step in the synthesis of II is the double-lithiation
of 2 in one step. Poirier et al. applied a sequential reaction
scheme (mono-lithiation, addition of electrophile, re-lithi-
ation, addition of electrophile) for the introduction of me-
thyl-, phenyl-, and trimethylsilyl-substituents in 2,7-
position.11 However, a sequential reaction scheme may
not be effective when DMF is the electrophile, because
the mono-adduct could react with the second equivalent of
lithiation reagent. Scanning several parameters of the
SYNLETT 2004, No. 4, pp 0735–0737
Advanced online publication: 10.02.2004
DOI: 10.1055/s-2004-817755; Art ID: G34303ST
© Georg Thieme Verlag Stuttgart · New York
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9.
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3.
2
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0
4

736
T. Glaser, I. Liratzis
LETTER
diffraction (Figure 3).12 In comparison to the molecular
structure of 2, the two MOM groups are located on differ-
ent sides of the naphthalene ring. The formyl groups are
almost coplanar to the plane of the naphthalene ring with
the C=O function tilted away from the MOM group. This
results in H···O contacts between the hydrogen atoms of
the formyl groups and the oxygen atoms O1 and O2 (2.43
and 2.41 Å, respectively).
Deprotection of the hydroxy groups was performed by
dissolving 3 in CH2Cl2 under an argon-blanketed atmo-
sphere and adding a solution of HCl in i-PrOH at 0 °C.
The resulting solution was warmed in the course of 4
hours. Removing of volatiles under reduced pressure re-
sulted in pure II in 97% yield (Scheme 1). The IR spec-
trum of II exhibits a C=O vibration at 1664 cm–1 in
comparison to 1686 cm–1 observed for 3. This indicates a
rotation of the formyl substituents by ca. 180° and the for-
mation of hydrogen bonds between the hydroxyl proton
and the oxygen atom of the formyl group in the unprotect-
ed dialdehyde II.
Scheme 1 Synthesis of II. a) 2.5 equiv NaH, 2.5 equiv MOMCl,
Et2O, DMF, 25 °C, 88%; b) 3 equiv n-BuLi, 3 equiv TMEDA, Et2O,
5 h, 0 °C; c) 6 equiv DMF, 4 h, 0 °C → 25 °C; d) HCl, 66%; e)
CH2Cl2, HCl–i-PrOH, 4 h, 0 °C → 25 °C, 97%.
reaction conditions (n-, sec-, or tert-BuLi, equivalents of
BuLi, equivalents of TMEDA, solvent, reaction tempera-
ture, reaction time, sequence of addition, stirring time,
temperature of DMF addition), we found a protocol for
the double-lithiation of 2 in one step.
Figure 3 Molecular structure of 3.
Attempts to use 2,7-diacetyl-1,8-dihydroxy-3,6-dimethyl-
naphthalene, which was obtained via a self-condensation
reaction of diacetylacetone, as building block for 2,7-di-
Schiff base derivatives of 1,8-naphthalenediol have been
reported to be unsuccessful.14 Only mono-Schiff base
products are formed upon condensation with mono-pri-
mary amines in either metal-free reactions or in the pres-
ence of Cu(II) or Pd(II). These problems might be
attributed to the relatively unreactive ketone functions in
2,7 position. In general, ketones react more slowly than al-
dehydes with amines to form imines. By using ketones, it
is often necessary to employ higher temperatures and
longer reaction times and to remove the water formed to
shift the equilibrium to the ketimine. Aldehydes react
more readily with amines to form aldimines. We have
tested the reactivity of the aldehyde functions of II by the
successful formation of 2,7-bis[(2-pyridinylmethyl)imi-
nomethyl]-1,8-naphthalinediol from the reaction of II and
2-aminomethylpyridine in a MeOH–CHCl3 mixture. In
this respect, our streamlined synthesis of the more reac-
tive dialdehyde II enables the investigation of di-Schiff
base formation. We are currently examining the potential
Figure 2 Molecular structure of 2.
Our first attempts involved the use of up to 8 equivalents
of n-BuLi because the di-lithiation of one ring-system was
thought to need strong conditions but this led only to an
unidentified mixture of products. Three equivalents of n-
BuLi and TMEDA were found to be sufficient if a rela-
tively dilute solution of 2 in Et2O was added dropwise at
0 °C to a highly concentrated solution of n-BuLi and
TMEDA in Et2O. After keeping this solution for 5 hours
at 0 °C, 6 equivalents of anhydrous DMF were added and
the resulting mixture was stirred for another 4 hours. After
careful adjustment of the pH to 7–8 by dilute deareated
HCl and standard workup, we obtained the pure dialde-
hyde 3 in 66% yield (Scheme 1).13 Recrystallization from
hot EtOH–n-hexane (10:1) gave large brown crystals of 3.
The structure of 3 was confirmed by single-crystal X-ray
Synlett 2004, No. 4, 735–737 © Thieme Stuttgart · New York

LETTER
Synthesis of 2,7-Diformyl-1,8-naphthalenediol
737
of dialdehyde II as building block for novel ligand sys-
tems to allow the preparation of trinuclear transition metal
complexes with interesting magnetic properties and cata-
lytic behavior.
References
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1,8-Bis(methoxymethoxy)naphthalene (2)
IR (KBr): 3056, 2954, 2956, 2925, 2853, 1580, 1461, 1372, 1262
(Car–O), 1155, 1047 (Cal–O), 971, 940, 920, 827, 762 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.49 (dd, J = 8.3, 1.0 Hz, 2 H, H4,
H5), 7.33 (dd, J = 8.3, 7.7 Hz, 2 H, H3, H6), 7.08 (dd, J = 7.7, 1.0
Hz, 2 H, H2, H7), 5.29 (s, 4 H, CH2), 3.60 (s, 6 H, CH3).
13C NMR (75 MHz, CDCl3): d = 153.6 (C1, C8), 137.5 (C4a), 126.1
(C3, C6), 122.7 (C4, C5), 119.3 (C8a), 112.8 (C2, C7), 96.5
(OCH2O), 56.3 (OCH3).
MS: m/z (%) = 248 (8) [M+], 172 (65), 115 (22), 45 (100).
Anal. Calcd for C14H16O4: C, 67.33; H, 6.50. Found: C, 67.51; H,
7.93.
2,7-Diformyl-1,8-bis(methoxymethoxy)naphthalene (3)
IR (KBr): 3076, 3055, 2978, 2957, 2936, 2881, 2830, 1686 (C=O),
1613, 1506, 1365, 1340, 1244 (Car–O), 1159, 1047 (Cal–O), 1064,
1016, 904, 855, 775 cm–1.
(3) See for example: Glaser, T.; Lügger, T. Inorg. Chim. Acta
2002, 337, 103; and references cited therein.
(4) (a) Crisp, G. T.; Turner, P. D. Tetrahedron 2000, 56, 407.
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J. Org. Chem. 2002, 67, 904.
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(b) Larrow, J. F.; Jacobsen, E. N.; Gao, Y.; Hong, Y.; Nie,
X.; Zepp, C. M. J. Org. Chem. 1994, 59, 1939.
1H NMR (300 MHz, CDCl3): d = 10.61 (d, J = 0.8 Hz, 2 H, CHO),
7.99 (d, J = 8.7 Hz, 2 H, H3, H6), 7.70 (dd, J = 8.7, 0.8 Hz, 2 H, H4,
H5), 5.23 (s, 4 H, CH2), 3.58 (s, 6 H, CH3).
13C NMR (90 MHz, CDCl3): d = 190.1 (CHO), 158.9 (C1, C8),
143.4 (C4a), 128.2 (C2, C7), 126.0 (C4, C5), 125.8 (C3, C6), 121.2
(C8a), 102.4 (OCH2O), 58.5 (OCH3).
MS: m/z (%) = 304 (13) [M+], 259 (40), 228 (100), 213 (58), 200
(92), 172 (59), 115 (38), 45 (46), 29 (17).
(7) Nagata, W.; Okada, K.; Aoki, T. Synthesis 1979, 365.
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Anal. Calcd for C16H16O6: C, 63.15; H, 5.30. Found: C, 63.34; H,
5.02.
2,7-Diformyl-1,8-naphthalenediol (II)
IR (KBr): 3349 (O–H), 3033, 2970, 2878, 1664 (C=O), 1640, 1576,
1415, 1225 (Car–O), 1200, 1141, 1048, 842, 820, 616, 590 cm–1.
(12) CCDC 220283 (2) and CCDC 220284 (3) contain the
supplementary crystallographic data of these structures.
These data can be obtained free of charge via
1H NMR (400 MHz, CDCl3): d = 12.65 (br s, 2 H, OH), 10.17 (s, 2
H, CHO), 7.74 (d, J = 8.6 Hz, 2 H, H3, H6), 7.30 (d, J = 8.6 Hz, 2
H, H4, H5).
13C NMR (100 MHz, CDCl3): d = 193.2 (CHO), 164.11 (C1, C8),
143.0 (C4a), 130.3 (C2, C7), 119.8 (C4, C5), 116.4 (C3, C6), 113.9
(C4a).
www.ccdc.cam.ac.uk/conts/retrieving.html [or from the
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK;
fax:+44(1223)336033; e-mail:deposit@ccdc.cam.ac.uk].
(13) 2,7-Diformyl-1,8-bis(methoxymethoxy)naphthalene (3).
A solution of 2 (2.00 g, 8.06 mmol) in Et2O (90 mL) was
added dropwise over a period of 3 h to a solution of n-BuLi
(2.5 M, 9.67 mL, 24 mmol) and TMEDA (3.63 mL, 24
mmol) in Et2O (10 mL) at 0 °C. After stirring the reaction
mixture for 5 h at r.t., DMF (3.76 mL, 24.17 mmol) was
added at 0 °C and the resulting mixture stirred for another 4
h at r.t. After addition of water (40 mL) and stirring for 1 h
at r.t., the pH of the reaction solution was raised to 7–8 by
addition of dilute HCl. Standard workup and column
chromatography gave 1.62 g (66%) of 3 as a brownish
yellow solid.
MS: m/z (%) = 216 (100) [M+], 187 (66), 142 (28), 114 (40).
Anal. Calcd for C12H8O4: C, 66.67; H, 3.73. Found: C, 66.75; H,
3.75.
Acknowledgment
This work was supported by the Fonds der Chemischen Industrie,
the Deutsche Forschungsgemeinschaft (priority program ‘Molecu-
lar Magnetism’), and the Dr. Otto Röhm Gedächtnisstiftung. The
continued support of Prof. Dr. F. E. Hahn is gratefully acknowled-
ged. Thanks are due to Tania Pape for skilful technical assistance.
(14) Hoskins, B. F.; McKenzie, C. J.; Robson, R. J. Chem. Soc.,
Dalton Trans. 1992, 3083.
Synlett 2004, No. 4, 735–737 © Thieme Stuttgart · New York