Versatile synthesis of 6-alkyl and aryl substituted pyridoxal derivatives

Article abstract of DOI:10.1055/s-2000-6228

A versatile and convenient procedure for the functional derivatization with carbon substituents at the 6-position of pyridoxal using a Grignard reaction upon a protected N-isobutoxycarbonyloxypyridoxal chloride and Heck reactions with protected 6-vinylpyr

Full text of DOI:10.1055/s-2000-6228

PAPER
119
Versatile Synthesis of 6-Alkyl and Aryl Substituted Pyridoxal Derivatives
Yong-Chul Kim, Kenneth A. Jacobson*
Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892-0810,
USA
Fax +1(301)4808422; E-mail:kajacobs@helix.nih.gov
Received 16 July 1999; revised 10 September 1999
a pivaloyl ester to afford 3. Oxidation of 3 with m-CPBA
Abstract: A versatile and convenient procedure for the functional
proceeded smoothly to the N-oxide derivative 4 with an
derivatization with carbon substituents at the 6-position of pyridox-
overall yield of 54% for the 3 steps. The activation of the
al using a Grignard reaction upon a protected N-isobutoxycarbony-
pyridine ring system through the conjugation of 4 with
isobutylchloroformate was followed by a Grignard reac-
tion in situ at –78°C. All three functional moieties, vinyl,
phenyl and benzyl, shown in the Scheme, were success-
fully introduced at the 6-position of protected pyridoxal to
give 6a-c, however, reaction with trimethylsilylthiazole7
gave unidentified mixtures.
loxypyridoxal chloride and Heck reactions with protected 6-
vinylpyridoxal has been developed.
Key words: pyridoxal, 6-substitution, P2 receptors, Grignard reac-
tion, Heck reaction, protecting groups, deprotection, N-oxides, het-
erocycles
Pyridoxal-a5-phosphate-6-phenylazo derivatives based
on the structure of PPADS1(1) (Figure) have been synthe-
sized and characterized as selective antagonists of P2 re-
ceptors,2 at which extracellular nucleotides bind as
neurotransmitters.3 Exploring the role of P2 receptors in
the nervous system will require ligands which are selec-
tive and potent at specific receptor subtypes.
In order to provide a variety of functional groups, 6a was
subjected to a Heck reaction with aromatic halides to give
the corresponding styryl derivatives 8a-c in 40-90%
yield. Finally, deprotection of pivaloyl and monomethyl-
acetal groups was easily accomplished using sequential
aqueous alkaline and acidic conditions to generate the 6-
substituted pyridoxal derivatives 7a-c and 9a-c, as a
mixture of aldehyde and intramolecular hemiacetal forms
in quantitative yields.
O
H
There are few examples of 6-substituted pyridoxal deriv-
atives. 6-Halogenated pyridoxal derivatives have been
prepared through a modified Schiemann reaction from 6-
aminopyridoxine and subsequent oxidation.8 A prepara-
tion of 6-(methyl)pyridoxal utilizing a Diels-Alder reac-
tion was reported.9 The present study reports a general
approach to functional derivatization at the 6-position of
pyridoxal. The phosphorylation of each pyridoxal analog
and the testing in biological systems, including P2 recep-
tor assays, are in progress.
O
P
HO
OH
R
O
1 : R=2,4-disulfonic acid
OH
H3C
N
N
N
Figure Structure of PPADS
In an effort to replace the unstable azo linkage of P2 re-
ceptor antagonists such as 1 with stable carbon bridges,
including the ethenyl moiety, derivatization at the 6-posi-
tion of pyridoxal was studied. Among the approaches
used to derivatize at the 6-position of pyridine com-
pounds, we selected Grignard reactions carried out on an
intermediate, N-isobutoxycarbonyloxypyridinium chlo-
ride4 5a (Scheme), because of its high reactivity and facile
generation of the corresponding pyridine derivatives 6a-
c from the intermediate of 1,6-dihydropyridines 5b. This
is accomplished by simply elevating the reaction temper-
ature (-78 to 25°C), after the substitution reaction at the 6
position without the need for oxidizing agents.5
1H NMR spectroscopy was performed on a Varian GEMINI-300
MHz spectrometer, and spectra were taken in DMSO-d6 or CDCl3.
Unless otherwise noted, chemical shifts are expressed as ppm
downfield from TMS, or relative ppm from DMSO (2.5 ppm).
Chemical-ionization (CI) mass spectrometry was performed with a
Finnigan 4600 mass spectrometer, and electron-impact (EI) mass
spectrometry with a VG7070F mass spectrometer at 6 kV. Elemen-
tal analyses were performed by Atlantic Microlab Inc. (Norcross,
GA). All melting points were determined with a Unimelt capillary
melting point apparatus (Arthur H. Thomas Co., PA) and are uncor-
rected.
3-Trimethylmethylcarbonylpyridoxal-N-oxide Monomethylac-
etal (4)
Pyridoxal Monomethylacetal of 2
A suspension of pyridoxal hydrochloride 2 (20.0 g, 0.098 mol) in
MeOH (125 mL) was refluxed for 1 h. After cooling, solid NaHCO3
(8.25 g, 0.098 mol) was added, and the mixture refluxed overnight.
The precipitated NaCl was removed by filtration, and the filtrate
Pyridoxal 2, was first protected as the monomethyl cyclic
acetal,6 in order to mask the aldehyde moiety while max-
imizing the accessibility for nucleophilic attack by Grig-
nard reagents, and the 3-hydroxyl group was protected as
Synthesis 2000, No. 1, 119–122 ISSN 0039-7881 © Thieme Stuttgart · New York

120
Y.-C. Kim, K. A. Jacobson
PAPER
O
H3CO
O
H3CO
O
H
O
O
O
O
iii
i, ii
HO
OH
H3C
N
H3C
N
H3C
N
O
2
3
4
H3CO
O
H3CO
O
H3CO
O
O
O
O
O
O
O
iv
Cl-
+
H3C
N
H3C
N
R1
H3C
N
R1
O
O
R1
6a : vinyl
COOiBu
COOiBu
6b : phenyl
6c : benzyl
5a
5b
v
O
H3CO
O
H
O
O
O
H
HO
H3C
v
vi
OH
6a
HO
OH
N
H3C
N
H3C
N
R1
R2
R2
R2
8a : phenyl
8b : 4-methoxyphenyl
8c : 4-methoxycarbonylphenyl 9c : 4-methoxycarbonylphenyl
R2
9a : phenyl
9b : 4-methoxyphenyl
R1
7a : vinyl
7b : phenyl
7c : benzyl
Reagents and conditions: i) MeOH/NaHCO3, reflux, 96%; ii) Pivaloyl-Cl/TEA/CH2Cl2, r. t., 98%; iii) m-CPBA/CH2Cl2, r. t., 57%; iv) isobutyl
chloroformate/ R1MgBr in THF, -78°C to r.t., 60-85%; v) 2% KOH in MeOH, r.t.; 10% H2SO4/acetone, 85°C, 80-100%; vi) R2X (X = I or
Br)/tri-O-tolylphosphine/Pd(OAc)2/TEA/MeCN, 100°C, 40-90%
Scheme
was concentrated causing crystallization of the product. Filtration of
the product gave 17.7 g of the pyridoxal monomethylacetal.
Oxidation of 3 to 4
A solution of crude 3 (24.5 g) and of m-CPBA (31.1 g, 0.108 mol)
in CH2Cl2 (150 mL) was stirred for 2 h at 25°C. The mixture was
sequentially washed with 1.0 M NaHSO3 and 1.0 M NaHCO3 solu-
tion, dried (Na2SO4), concentrated to dryness and the product was
crystallized in hexanes/EtOAc to give 15.0 g (54% for 3 steps) of 4
as a white solid; mp 125°C.
+
MS (CI, NH3): m/z = 182 (M+ + 1), 199 (M + NH4 ).
1H NMR (CDCl3): d = 2.53 (3 H, s, CH3), 3.45 (3 H, s, OCH3), 5.16
(2 H, ABq, J = 12.7, 41.3 Hz, CH2O), 6.27 (1 H, s, CH), 8.07 (1 H,
s, H-6).
MS (CI, NH3): m/z = 282 (M+ + 1).
3-Trimethylcarbonylpyridoxal Monoacetal 3
To a suspension of the pyridoxal monoacetal (18 g, 0.097 mol) ob-
tained as above and Et3N (20.8 mL, 0.149 mol) in anhyd CH2Cl2
(150 mL) was added pivaloyl chloride (13.6 mL, 0.0109 mol) at
0°C. After the complete addition, the mixture became a clear color-
less solution. The stirring was continued for an additional 1 h at
25°C, and the mixture was washed with brine, dried (Na2SO4) and
concentrated to dryness to give 24.5 g of crude 3, which was suffi-
ciently pure for the next step.
HRMS (EI): m/z calcd for C14H19NO5: 281.1263; found: 281.1271.
1H NMR (CDCl3): d = 1.41 [9 H, s, (CH3)3], 2.37 (3 H, s, CH3), 3.39
(3 H, s, OCH3), 5.13 (2 H, ABq, J = 12.7, 41.3 Hz, CH2O), 6.04 (1
H, s, CH), 8.19 (1 H, s, H-6).
3-Trimethylmethylcarbonyl-6-(vinyl)pyridoxal Monomethyl-
acetal (6a); Typical Procedure for Grignard Reaction
+
MS (CI, NH3): m/z = 266 (M+ + 1), 283 (M + NH4 ).
To a stirred solution of 4 (11 g, 0.0391 mol) in anhyd THF (100 mL)
at –78°C was added isobutylchloroformate (5.17 mL, 0.391 mol)
under N2. After stirring for 30 min, a 1.0 M solution of vinylmagne-
sium bromide in THF (78.2 mL, 0.782 mol) was added rapidly to
the mixture, and the stirring was continued for 1 h at –78°C and for
1 h at 25°C. The mixture was partitioned between Et2O and satd aq
1H NMR (CDCl3): d = 1.42 [9 H, s, C(CH3)3], 2.46 (3 H, s, CH3),
3.39 (3 H, s, OCH3), 5.18 (2 H, ABq, J = 12.7, 41.3 Hz, CH2O), 6.10
(1 H, s, CH), 8.37 (1 H, s, H-6).
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PAPER
Versatile Synthesis of 6-Alkyl and Aryl Substituted Pyridoxal Derivatives
121
NaHCO3, and the Et2O layer was dried (Na2SO4) and concentrated
to dryness. The crude product was purified by silica gel flash col-
umn chromatography with an elution of hexanes/EtOAc (10:1) to
give 6.4 g (56%) of 6a as a white solid; mp 83°C.
(23 mg, 0.076 mmol), 60 mg (40%) of 8b was obtained as a white
solid; mp 165°C.
MS (CI, NH3): m/z = 398 (M+ + 1).
Anal. Calcd for C23H27NO5: C 69.50, H 6.85, N 3.52. Found: C
69.69, H 6.97, N 3.43.
MS (CI, NH3): m/z = 292 (M+ + 1).
Anal. Calcd for C16H21NO4: C 65.96, H 7.27, N 4.81. Found: C
65.96, H 7.19, N 4.76.
1H NMR (CDCl3): d = 1.41 [9 H, s, C(CH3)3], 2.45 (3 H, s, CH3),
3.38 (3 H, s, OCH3), 5.22 (2 H, ABq, J = 12.7, 41.3 Hz, CH2O), 5.56
(1 H, d, J = 11.4 Hz, =CH2), 5.99 (1 H, d, J = 17.5 Hz, =CH2), 6.09
(1 H, s, CH), 6.72 (1 H, dd, J = 11.4, 17.5 Hz, CH= ).
1H NMR (CDCl3): d = 1.41 [9 H, s, C(CH3)3], 2.47 (3 H, s, CH3),
3.38 (3 H, s, OCH3), 3.85 (3 H, s, OCH3), 5.28 (2 H, ABq, J = 12.7,
45.0 Hz, CH2O), 6.12 (1 H, d, J = 1.95 Hz, CH), 6.85 (1 H, d,
J = 16.3 Hz, =CH), 6.92 (2 H, d, J = 8.6 Hz, C6H5), 7.44 (1 H, d,
J = 16.0 Hz, =CH), 7.52 (2 H, d, J = 8.7 Hz, C6H5).
3-Trimethylmethylcarbonyl-6-{(E)-[2-(4-methoxycarbon-
yl)phenyl]ethenyl}pyridoxal Monomethylacetal (8c)
Starting with 6a (290 mg, 1.0 mmol), methyl 4-iodobenzoate (270
mg, 1.0 mmol), Pd(OAc)2 (13 mg, 0.057 mmol), and tri-O-
tolylphosphine (70 mg, 0.228 mmol), 180 mg (42%) of 8b was ob-
tained as a white solid; mp 149°C.
3-Trimethylmethylcarbonyl-6-(phenyl)pyridoxal Monomethyl-
acetal (6b)
Starting with 4 (1 g, 3.56 mmol), isobutylchloroformate (0.45 mL,
3.37 mmol) and 2.0 M solution of phenylmagnesium chloride in
THF (3.55 mL, 7.10 mmol), 1.03 g (85%) of 6b was obtained as a
white solid; mp 103°C (dec.).
MS (CI, NH3): m/z = 426 (M+ + 1).
MS (CI, NH3): 342 (M+ + 1).
Anal. Calcd for C24H27NO6: C 67.75, H 6.40, N 3.29. Found: C
67.71, H 6.42, N 3.27.
Anal. Calcd for C20H23NO4: C 70.36, H 6.79, N 4.10. Found: C
70.45, H 6.81, N 4.16.
1H NMR (CDCl3): d = 1.42 [9 H, s, C(CH3)3], 2.51 (3 H, s, CH3),
3.42 (3 H, s, OCH3), 5.32 (2 H, ABq, J = 13.6, 67.4 Hz, CH2O), 6.11
(1 H, s, CH), 7.38-7.49 (3 H, m, C6H5), 7.70 (2 H, d, J = 6.8 Hz,
C6H5).
1H NMR (CDCl3): d = 1.41 [9 H, s, C(CH3)3], 2.48 (3 H, s, CH3),
3.40 (3 H, s, OCH3), 3.93 (3 H, s, OCH3), 5.30 (2 H, ABq, J = 13.7,
43.0 Hz, CH2O), 6.12 (1 H, d, J = 1.95 Hz, CH), 7.07 (1 H, d,
J = 15.6 Hz, =CH), 7.54 (1 H, d, J = 15.6 Hz, =CH), 7.63 (2 H, d,
J = 8.8 Hz, C6H5), 8.05 (2 H, d, J = 8.8 Hz, C6H5).
3-Trimethylmethylcarbonyl-6-(benzyl)pyridoxal Monomethyl-
acetal (6c)
Starting with 4 (1g, 3.56 mmol), isobutylchloroformate (0.45 mL,
3.37 mmol) and 2.0 M solution of benzylmagnesium chloride in
THF (3.55 mL, 7.10 mmol), 0.77 g (61%) of 6c was obtained as a
colorless oil.
6-(Vinyl)pyridoxal (7a); Typical Procedure for Deprotection
A solution of 6a (50 mg, 0.172 mmol) in 2% methanolic KOH so-
lution (1 mL) was stirred for 2 h at 25°C. The mixture was diluted
with CH2Cl2 (10 mL), passed through silica gel (10 mL) and washed
with CH2Cl2/MeOH (10:1). The filtrate was concentrated to dry-
ness, and the crude product was dissolved in 1% H2SO4 (2 mL) in
acetone/H2O and heated at 85°C for 24 h. After cooling, the solution
was applied to a ion-exchange column of Amberlite CG-50 (H+
form). The resin was washed with H2O until free of H2SO4 acid and
the product was eluted with 10% AcOH in H2O to give after
evaporation 27 mg of 7a (81%) as a light yellow solid; mp 128°C
(dec.).
MS (CI, NH3): m/z = 356 (M+ + 1).
Anal. Calcd. for C21H25NO4: C 70.96, H 7.09, N 3.94. Found: C
71.09, H 7.07, N 3.94.
1H NMR (CDCl3): d = 1.39 [9 H, s, C(CH3)3], 2.45 (3 H, s, CH3),
3.33 (3 H, s, OCH3), 4.09 (2 H, s, CH2Ph), 4.78 (2 H, ABq, J = 12.7,
38.09 Hz, CH2O), 6.00 (1 H, m, CH), 7.18-7.31 (5 H, m, C6H5).
HRMS (EI): m/z Calcd for C10H11NO3: 193.0739, found: 193.0730.
1H NMR (DMSO-d6): d = 2.37 (3 H, s, CH3), 5.03 (2 H, ABq,
J = 12.7, 52.7 Hz, CH2O), 5.33 (1 H, d, J = 10.7 Hz, =CH2), 5.76 (1
H, d, J = 17.6 Hz, =CH2), 6.40 (0.5 H, d, J = 5.9 Hz, CH of hemiac-
etal form, ratio of acetaldehyde/acetal form), 6.62 (1 H, dd,
J = 10.7, 17.6 Hz, CH=), 9.71 (0.5 H, s, CHO).
3-Trimethylmethylcarbonyl-6-[(E)-(2-phenyl)ethenyl]pyridox-
al Monomethylacetal (8a); Typical Procedure for Heck Reac-
tion
A suspension of 6a (120 mg, 0.41 mmol), iodobenzene (47 mL, 0.41
mmol), Pd(OAc)2 (4.7 mg, 0.021 mmol), and tri-O-tolylphosphine
(25 mg, 0.084 mmol) in Et3N (1 mL) and MeCN (1 mL) in a tightly
sealed test tube was heated at 100°C for 48 h. After cooling, the
mixture was diluted in CHCl2 (25 mL) and filtered through a Celite
bed. The filtrate was concentrated and purified by preparative TLC
with hexanes/EtOAc (2:1) to give 0.14 g (93%) of 8a as a white sol-
id; mp 91°C.
6-(Phenyl)pyridoxal (7b)
Starting with 6b (50 mg, 0.146 mmol), 39 mg (~ 100%) of 7b was
obtained as a light yellow solid ; mp 174°C (dec.).
HRMS (EI): m/z Calcd for C14H13NO3: 243.0895, found: 243.0893.
1H NMR (DMSO-d6): d = 2.46 (3 H, s, CH3), 5.17 (2 H, ABq,
J = 12.7, 98.6 Hz, CH2O), 6.44 (0.75 H, s, CH of hemiacetal form,
ratio of aldehyde/acetal form, 1:3), 7.33-7.47 (3 H, m, C6H5), 7.70
(2 H, d, J = 7.8 Hz, C6H5), 9.70 (0.25 H, s, CHO).
MS (CI, NH3): m/z = 368 (M+ + 1).
Anal. Calcd for C22H25NO4: C 71.91, H 6.86, N 3.81. Found: C
71.89, H 6.94, N 3.74.
6-(Benzyl)pyridoxal (7c)
Starting with 6c (50 mg, 0.141 mmol), 38 mg (~ 100%) of 7c was
obtained as a light yellow solid ; mp 116°C.
1H NMR (CDCl3): d = 1.40 [9 H, s, C(CH3)3], 2.47 (3 H, s, CH3),
3.38 (3 H, s, OCH3), 5.29 (2 H, ABq, J = 12.7, 45.0 Hz, CH2O), 6.11
(1 H, d, J = 1.95 Hz, CH), 6.98 (1 H, d, J = 16.6 Hz, =CH), 7.30-
7.40 (3 H, m, C6H5), 7.49 (1 H, d, J = 16.6 Hz, =CH), 7.56 (2 H, d,
J = 7.8 Hz, C6H5).
HRMS (EI): m/z Calcd for C15H15NO3: 257.1052, found: 257.1042.
1H NMR (DMSO-d6): d = 2.35 (3 H, s, CH3), 3.89 (1 H, s, CH2),
4.76 (2 H, ABq, J = 12.7, 45.9 Hz, CH2O), 6.36 (0.4 H, d, J = 5.9
Hz, CH of hemiacetal form, ratio of aldehyde/acetal form, 1:1.5, ),
7.18-7.29 (5 H, m, C6H5), 9.34 (0.6 H, s, CHO).
3-Trimethylmethylcarbonyl-6-{(E)-[2-(4-methoxy)phenyl]ethe-
nyl}pyridoxal Monomethylacetal (8b)
Starting with 6a (110 mg, 0.38 mmol), p-iodoanisole (89 mg, 0.38
mmol), Pd(OAc)2 (4.3 mg, 0.019 mmol), and tri-O-tolylphosphine
Synthesis 2000, No. 1, 119–122 ISSN 0039-7881 © Thieme Stuttgart · New York

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Y.-C. Kim, K. A. Jacobson
PAPER
6-[(E)-2-(Phenyl)ethenyl]pyridoxal (9a)
Starting with 8a (50 mg, 0.136 mmol), 40 mg (~ 100%) of 9a was
obtained as a yellow solid; mp 145°C (dec.).
References
(1) Lambrecht, G.; Ardanuy, U.; Bäumert, H.G.; Bo, X.; Hoyle,
C.H.V.; Nickel, P.; Pfaff, O.; Ralevic, V.; Windschief, U.;
Ziganshin, A.U.; Ziyal, R.; Mutschler, E.; Burnstock, G. In
Perspectives in Receptor Research; Giardinà, D., Piergentili,
S.; Pigini, M., Eds.; Elsevier: Amsterdam, 1996; p 337.
(2) Kim, Y.-C.; Camaioni, E.; Ziganshin, A. U.; Ji, X. D.; King,
B. F.; Wildman, S. S.; Rychkov, A.; Yoburn, J.; Kim, H.O.;
Mohanram, A.; Harden T. K.; Boyer, J. L.; Burnstock, G.;
Jacobson, K. A. Drug Develop. Res. 1998, 45, 52.
(3) Barnard, E. A.; Simon, J.; Webb, T. E. Mol. Neurobiol. 1997,
15, 103.
(4) Webb, T. R. Tetrahedron Lett. 1985, 26, 3191.
(5) An attempt to employ the N-methoxycarbonylpyridinium
chloride from compound 3 as a substrate for the
Grignard reaction was not successful:
Yamaguchi, Y.; Nakazono, Y.; Kawanisi, M. Tetrahedron
Lett. 1983, 24, 1801.
(6) Heyl, D.; Luz, E.; Harris, S. A.; Folkers, K. J. Am. Chem. Soc.
1951, 73, 3430.
HRMS (EI): m/z Calcd for C16H15NO3: 269.1052, found: 269.1065.
1H NMR (DMSO-d6): d = 2.51 (3 H, s, CH3), 5.25 (2 H, ABq,
J = 13.7, 42.0 Hz, CH2O), 6.51 (1 H, s, CH of hemiacetal form),
7.17 (1 H, d, J = 16.6 Hz, =CH), 7.32 (1 H, d, J = 16.6 Hz, CH=),
7.25-7.45 (3 H, m, C6H5), 7.67 (2 H, d, J = 7.8 Hz, C6H5).
6-{[(E)-2-(4-Methoxy)phenyl]ethenyl}pyridoxal (9b)
Starting with 8b (50 mg, 0.125 mmol), 41 mg (~ 100%) of 9b was
obtained as a orange solid ; mp >300°C.
HRMS (EI): m/z Calcd for C17H17NO4: 299.1157, found: 299.1151.
1H NMR (DMSO-d6): d = 2.57 (3 H, s, CH3), 3.81 (3 H, s, OCH3),
5.31 (2 H, ABq, J = 13.7, 42.0 Hz, CH2O), 6.57 (1 H, s, CH of hemi-
acetal form), 7.03 (2 H, d, J = 7.8 Hz, C6H5), 7.09 (1 H, d, J = 16.6
Hz, CH=), 7.27 (1 H, d, J = 16.6 Hz, =CH), 7.65 (2 H, d, J = 7.8 Hz,
C6H5).
6-{(E)-2-(4-Methoxycarbonyl)phenyl]ethenyl}pyridoxal (9c)
Starting with 8c (50 mg, 0.117 mmol), 37 mg (97%) of 9c was ob-
tained as a light yellow solid; mp 263°C (dec.).
(7) Dondoni, A.; Dall’Occo, T.; Galliani, G.; Mastellari, A.;
Medici, A. Tetrahedron Lett. 1984, 25, 3637.
HRMS (EI): m/z Calcd for C18H17NO5: 327.1107, found: 327.1119.
(8) Korytnyk, W.; Srivastava, S. C. J. Med. Chem. 1973, 16, 638.
(9) Doktorova, N. D.; Ionova, L. V.; Karpeisky, M. YA.;
Padyukova, N. SH.; Turchin, K. F.; Florentiev, V. L.
Tetrahedron 1969, 25, 3527.
1H NMR (DMSO-d6): d = 2.42 (3 H, s, CH3), 3.85 (3 H, s, OCH3),
5.16 (2 H, ABq, J = 13.7, 42.0 Hz, CH2O), 6.43 (0.3 H, s, CH of
hemiacetal form, ratio of aldehyde/acetal form, 1:2), 7.22 (1 H, d,
J = 16.6 Hz, =CH), 7.37 (1 H, d, J = 16.6 Hz, =CH), 7.78 (2 H, d,
J = 8.8 Hz, C6H5), 7.94 (2 H, d, J = 8.8 Hz, C6H5), 9.86 (0.7 H, s,
CHO).
Article Identifier:
1437-210X,E;2000,0,01,0119,0122,ftx,en;M01799SS.pdf
Acknowledgement
The authors would like to thank to Noel Whittaker for mass spectro-
scopic measurements.
Synthesis 2000, No. 1, 119–122 ISSN 0039-7881 © Thieme Stuttgart · New York