Synthesis of 5-(ω-sulfhydrylalkyl)salicylaldehydes as precursors for the preparation of alkanethiol-modified metal salens

Article abstract of DOI:10.1016/S0040-4039(01)01178-9

Using multistep syntheses, we obtained two alkanethiol-modified salicylaldehydes, namely 5-(2-sulfhydrylethyl)salicylaldehyde and 5-(6-sulfhydrylhexyl)salicylaldehyde. These compounds are precursors for the preparation of alkanethiol-substituted metal sal

Full text of DOI:10.1016/S0040-4039(01)01178-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 6065–6067
Synthesis of 5-(v-sulfhydrylalkyl)salicylaldehydes as precursors
for the preparation of alkanethiol-modified metal salens
Chang Ji and Dennis G. Peters*
Department of Chemistry, Indiana University, Bloomington, IN 47405, USA
Received 8 June 2001; accepted 18 June 2001
Abstract—Using multistep syntheses, we obtained two alkanethiol-modified salicylaldehydes, namely 5-(2-sulfhydrylethyl)-
salicylaldehyde and 5-(6-sulfhydrylhexyl)salicylaldehyde. These compounds are precursors for the preparation of alkanethiol-sub-
stituted metal salens, which can potentially be used to form surface-modified gold electrodes. © 2001 Elsevier Science Ltd. All
rights reserved.
For both fundamental and practical reasons, the behav-
ior of surface-modified electrodes has been of consider-
able interest.1 Among the many methods used to
prepare surface-modified electrodes, the gold–alkane-
thiol self-assembly method is particularly attractive.2
Recently, our group has investigated the catalytic
reduction of halogenated organic compounds by elec-
trogenerated low-valent metal salens.3–8 We thought it
would be interesting to synthesize alkanethiol-substi-
tuted metal salens so that we can use these compounds
to prepare and study surface-modified gold electrodes.
salicylaldehyde (4) was formed via the use of Grignard
reagent, paraformaldehyde, and triethylamine;10 the
product was purified by silica-gel column chromatogra-
phy (5% ethyl acetate–95% hexanes) and was recrystal-
lized from ethanol. Finally, 4 was converted to 5 in
high yield through the use of thiourea to afford the
isothiuronium salt, followed by treatment with base.11
All key compounds were characterized by means of
GC–MS and NMR spectrometry.12
Scheme 2 shows the synthetic route to 5-(6-sulfhydryl-
hexyl)salicylaldehyde (10). We prepared 4-(6-bromo-
hexyl)phenol (8) via Friedel–Crafts acylation of anisole
with 6-bromohexanoyl chloride (Aldrich, 97%), fol-
lowed by reduction of the carbonyl group2 and conver-
sion of the anisole to the phenol.13 Subsequent synthetic
steps are similar to those for 5-(2-sulfhydrylethyl)-
salicylaldehyde. GC–MS and NMR data were collected
for compounds 6–10.14 Since v-haloalkanoyl halides
are commercially available, one can obtain 5-(v-
sulfhydrylalkyl)salicylaldehydes with up to eight meth-
ylene groups.
A general procedure to synthesize metal salens involves
reacting salicylaldehyde with ethylenediamine to give
the salen ligand, which is subsequently treated with a
metal acetate to form the metal salen. To prepare an
alkanethiol-modified metal salen, one must begin with
an v-sulfhydrylalkyl-substituted salicylaldehyde. In this
paper, we describe procedures for the high-yield synthe-
sis of salicylaldehydes with alkanethiol side chains of
various lengths, and these approaches have been used
to obtain two previously unreported compounds—
namely, 5-(2-sulfhydrylethyl)salicylaldehyde and 5-(6-
sulfhydrylhexyl)salicylaldehyde.
In conclusion, we have synthesized 5-(2-sulfhy-
drylethyl)salicylaldehyde and 5-(6-sulfhydrylhexyl)-
salicylaldehyde as precursors for the preparation of
alkanethiol-modified metal salens (which can be poten-
tially used to modify the surfaces of gold electrodes),
and we have demonstrated the feasibility of an
approach consisting of simple steps to afford the
desired products in relatively high yields. It should be
convenient for one to obtain other 5-(v-sulfhydryl-
alkyl)salicylaldehydes by choosing suitable v-haloalkan-
oyl halides with various numbers of methylene groups
as the starting compounds.
Synthesis of 5-(2-sulfhydrylethyl)salicylaldehyde (5) was
carried out by the method outlined in Scheme 1. We
prepared 4-(2-iodoethyl)phenol (2) by refluxing a mix-
ture of 4-methoxyphenethyl alcohol (1, Aldrich, 99%)
and 47% hydriodic acid.9 Then 5-(2-iodoethyl)-
Keywords: 5-(v-sulfhydrylalkyl)salicylaldehydes; alkanethiol-modified
metal salens; surface-modified electrodes.
* Corresponding author. Tel.: +1-812-8559671; fax: +1-812-8558300;
e-mail: peters@indiana.edu
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01178-9

6066
C. Ji, D. G. Peters / Tetrahedron Letters 42 (2001) 6065–6067
Scheme 1.
Scheme 2.

C. Ji, D. G. Peters / Tetrahedron Letters 42 (2001) 6065–6067
6067
References
13. Landini, D.; Montanari, F.; Rolla, F. Synthesis 1978,
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14. Product 6: GC–MS (70 eV) m/z 286, M+ (0.3%); 284, M+
(0.3%); 205, [M−Br]+ (2%); 163, [M−(CH2)3Br]+ (2%);
150, [M−CH2ꢀCH(CH2)2Br]+ (68%); 135, [M−(CH2)5Br]+
(100%); 107, [M−CO(CH2)5Br]+ (6%); 92, [M−
1. Molecular Design of Electrode Surfaces; Murray, R. W.
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3. Butler, A. L.; Peters, D. G. J. Electrochem. Soc. 1997,
144, 4212–4217.
4. Bhattacharya, D.; Samide, M. J.; Peters, D. G. J. Elec-
troanal. Chem. 1998, 441, 103–107.
5. Alleman, K. S.; Peters, D. G. J. Electroanal. Chem. 1998,
451, 121–128.
6. Alleman, K. S.; Peters, D. G. J. Electroanal. Chem. 1999,
460, 207–213.
7. Samide, M. J.; Peters, D. G. J. Pharm. Biomed. Anal.
1999, 19, 193–203.
8. Klein, L. J.; Alleman, K. S.; Peters, D. G.; Karty, J. A.;
Reilly, J. P. J. Electroanal. Chem. 2000, 481, 24–33.
9. Cheng, C.-S.; Ferber, C.; Bashford, Jr., R. I.; Grillot, G.
F. J. Am. Chem. Soc. 1951, 73, 4081–4084.
10. Wang, R. X.; You, X. Z.; Meng, Q. J.; Mintz, E. A.; Bu,
X. R. Synth. Commun. 1994, 24, 1757–1760.
11. Cossar, B. C.; Fournier, J. O.; Fields, D. L.; Reynolds,
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1
CO(CH2)5Br−CH3]+ (9%); H NMR (CDCl3): l 7.94 and
6.94 (2 d, 2H each, ArH), 3.87 (s, 3H, OCH3), 3.43 (t,
2H, CH2Br), 2.94 (t, 2H, COCH2), 1.92 (q, 2H,
CH2CH2Br), 1.76 (q, 2H, CH2CH2CH2Br), 1.53 (q, 2H,
COCH2CH2). Product 7: GC–MS (70 eV) m/z 272, M+
(8%); 270, M+ (8%); 121, [M−(CH2)5Br]+ (100%); 1H
NMR (CDCl3): l 7.08 and 6.82 (2 d, 2H each, ArH), 3.78
(s, 3H, OCH3), 3.39 (t, 2H, CH2Br), 2.55 (t, 2H, ArCH2),
1.84 (q, 2H, CH2CH2Br), 1.59 (q, 2H, ArCH2CH2), 1.45
(q, 2H, CH2CH2CH2Br), 1.34 (q, 2H, ArCH2CH2CH2).
Product 8: GC–MS (70 eV) m/z 258, M+ (7%); 256, M+
1
(7%); 107, [M−(CH2)5Br]+ (100%); H NMR (CDCl3): l
7.03 and 6.75 (2 d, 2H each, ArH), 3.39 (t, 2H, CH2Br),
2.53 (t, 2H, ArCH2), 2.06 (s, 1H, OH), 1.84 (q, 2H,
CH2CH2Br), 1.58 (q, 2H, ArCH2CH2), 1.45 (q, 2H,
CH2CH2CH2Br), 1.33 (q, 2H, ArCH2CH2CH2). Product
9: GC–MS (70 eV) m/z 286, M+ (9%); 284, M+ (9%); 135,
[M−(CH2)5Br]+ (100%); 1H NMR (CDCl3): l 10.86 (s, 1H,
ArOH), 9.87 (s, 1H, CHO), 7.36–7.34 and 6.92 (m and d,
2H and 1H, respectively, ArH), 3.41 (t, 2H, CH2Br), 2.60
(t, 2H, ArCH2), 1.86 (q, 2H, CH2CH2Br), 1.63 (q, 2H,
ArCH2CH2), 1.48 (q, 2H, CH2CH2CH2Br), 1.35 (q, 2H,
ArCH2CH2CH2). Product 10: GC–MS (70 eV) m/z 238,
M+ (12%); 187, [M−H2O–SH]+ (5%); 173, [M−H2O–
CH2SH]+ (5%); 135, [M−(CH2)5SH]+ (100%); 1H NMR
(CDCl3): l 10.86 (s, 1H, ArOH), 9.87 (s, 1H, CHO),
7.36–7.33 and 6.91 (m and d, 2H and 1H, respectively,
ArH), 2.60 (t, 2H, ArCH2), 2.52 (q, 2H, CH2SH), 1.61 (q,
4H, ArCH2CH2 and CH2CH2SH), 1.46–1.30 (2 m, 2H
and 3H, respectively, ArCH2CH2CH2, CH2CH2CH2SH,
and SH).
12. Product 2: mp 111–112°C; GC–MS (70 eV) m/z 248, M+
(9%); 121, [M−I]+ (100%); 107, [M−CH2I]+ (19%); 1H
NMR (CDCl3): l 7.06 and 6.78 (2 d, 2H each, ArH), 4.76
(s, 1H, OH), 3.31 (t, 2H, CH2I), 3.10 (t, 2H, ArCH2).
Product 4: mp 78–79°C; GC–MS (70 eV) m/z 276, M+
(15%); 149, [M−I]+ (100%); 135, [M−CH2I]+ (14%); 121,
1
[M−CH2CH2I]+ (7%); H NMR (CDCl3): l 10.96 (s, 1H,
ArOH), 9.89 (s, 1H, CHO), 7.38–7.36 and 6.96 (s and 2 d,
1H each, ArH), 3.35 (t, 2H, CH2I), 3.16 (t, 2H, ArCH2).
Product 5: GC–MS (70 eV) m/z 182, M+ (24%); 164,
[M−H2O]+ (17%); 135, [M−CH2SH]+ (100%); 1H NMR
(CDCl3): l 10.91 (s, 1H, ArOH), 9.89 (s, 1H, CHO),
7.38–7.37 and 6.96 (dd and 2 d, 1H each, ArH), 2.92 (t,
2H, ArCH2), 2.79 (q, 2H, CH2SH), 1.36 (t, 1H, CH2SH).
.