Microwave Assisted Improved Synthesis of 6-Formylpterin and Other Heterocyclic Mono- and Di-aldehydes

Article abstract of DOI:10.1081/SCC-120015779

2-Pivaloylamino-6-formylpterin (1a) and a series of other important heterocyclic aldehydes (2a, 3a, 4a, 6a, and 7a) have been synthesized in good yield by microwave assisted selenium dioxide oxidation. Interestingly, 2-methylpyrazine gives 2-pyrazinecarboxylic acid (5a) under the similar condition.

Full text of DOI:10.1081/SCC-120015779

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Microwave Assisted Improved Synthesis of 6-
Formylpterin and Other Heterocyclic Mono- and Di-
aldehydes
a
a
Shyamaprosad Goswami & Avijit Kumar Adak
a
Department of Chemistry , Bengal Engineering College(Deemed University) , Howrah, West
Bengal, India
Published online: 17 Aug 2006.
To cite this article: Shyamaprosad Goswami & Avijit Kumar Adak (2003) Microwave Assisted Improved Synthesis of 6-
Formylpterin and Other Heterocyclic Mono- and Di-aldehydes, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 33:3, 475-480, DOI: 10.1081/SCC-120015779
To link to this article: http://dx.doi.org/10.1081/SCC-120015779
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Õ
SYNTHETIC COMMUNICATIONS
Vol. 33, No. 3, pp. 475–480, 2003
Microwave Assisted Improved Synthesis of
-Formylpterin and Other Heterocyclic Mono-
and Di-aldehydes
6
Shyamaprosad Goswami* and Avijit Kumar Adak
Department of Chemistry, Bengal Engineering College
(
Deemed University), Howrah, West Bengal, India
ABSTRACT
2
-Pivaloylamino-6-formylpterin (1a) and a series of other important
heterocyclic aldehydes (2a, 3a, 4a, 6a, and 7a) have been synthesized
in good yield by microwave assisted selenium dioxide oxidation.
Interestingly, 2-methylpyrazine gives 2-pyrazinecarboxylic acid (5a)
under the similar condition.
Key Words: Selenium dioxide; 6-formylpterin; Heterocyclic alde-
hyde; Microwave.
*
Correspondence: Shyamaprosad Goswami, Department of Chemistry, Bengal
Engineering College (Deemed University), Howrah-711 103, West Bengal, India;
Fax: 091336682916; E-mail: spgoswamical@yahoo.com.
4
75
DOI: 10.1081/SCC-120015779
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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76
Goswami and Adak
Microwave assisted organic reactions have been widely studied in
[
1]
various chemical reactions e.g., condensation, addition, cross-coupling
reaction, cyclo-addition, aromatic substitution, esterification, oxidation
and reduction etc. However, selenium dioxide oxidation of allylic methyl
to aldehyde group in heterocyclic compounds in solvent free condition
remains unexplored. Heterocyclic aldehydes are important intermediates
for the synthesis of biologically active molecules. 6-Formylpterin is a pre-
[
2]
cursor of the pteridine substrate of dihydropteroate biosynthesis. In our
[3]
[4]
synthetic studies on molybdenum cofactor which has a C6-substituted
pterin ring system, we found this procedure is efficient and economic for
the synthesis of 6-formylpterin.
RESULTS AND DISCUSSION
For the first time, we report here a useful, straightforward and eco-
nomic procedure for the synthesis of 2-pivaloylamino-6-formylpterin
(
1a), a new functionalized pyridine aldehyde (2-pivaloylamino-pyridine-
-carboxaldehyde, 3a) and a series of other important heterocyclic mono-
and di-aldehydes (2a, 4a, 6a and 7a) in microwave condition.
6
The yields are better than conventional heating of the compounds
with selenium dioxide in suitable solvents like dioxan, pyridine or acetic
acid. Microwave assisted selenium dioxide oxidation is found to be much
better in terms of improved reaction rates, less hazardous work-up and
formation of cleaner products. However, in case of 2-methylpyrazine the
only isolated product is 2-pyrazinecarboxylic acid (5a). Alkaline hydro-
lysis of 1a and 3a afforded the corresponding amino aldehydes. The
reaction conditions and yields are summarized in Table 1. All the
1
compounds are well characterized by H NMR and other spectroscopic
studies. Their melting points and NMR-spectra (for known compounds)
[
5–7]
were compared with those reported
(see experimental).
In conclusion, we have developed an efficient new route for the synth-
esis of a series of heterocyclic mono- and di-aldehydes which takes very
short time for completion compared to conventional procedures.
EXPERIMENTAL
General Procedure for Conversion of Aromatic Methyl to Aldehyde
The compound with stoichiometric amounts of selenium dioxide was
mixed thoroughly in a conical flask (for Entry 1 the mixture was moistened

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6
-Formylpterin
477

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78
Goswami and Adak
with glacial acetic acid and for Entries 4, 6 and 7 the mixture was mois-
tened with dioxan) and was irradiated in the microwave oven which resulted
solid mass. The solid was dissolved in chloroform, filtered through a pad
3–4 cm) of celite and washed well with chloroform. The combined filtrate
a
(
and washings were evaporated to dryness by the rotary evaporator and
purified by column chromatography using silica gel (60–120 or 100–200
mesh), afforded the corresponding mono- and di-aldehydes.
Representative Procedure for Conversion of 2-Methylquinoxaline to
Quinoxaline-2-carboxaldehyde
A mixture of 2-methylquinoxaline 2 (1.01 g, 7.01 mmol) and selenium
dioxide (0.84 g, 7.71 mmol) was irradiated at 450W for 12 min which
produced a solid mass. The residue leftwas dissolved in chloroform
and filtered through a pad (3–4 cm) of celite. The filtrate was evaporated
to dryness by the rotary evaporator and purified by column chromatog-
raphy (silica gel, 100–200 mesh) using chloroform–petroleum ether (3:1)
as an eluent( R ¼ 0.3) which afforded white crystalline solid 2a (0.98 g,
f
ꢀ
[6]
ꢀ
1
9
0%). M.p. 68–69 C (lit. 109 C). H NMR (CDCl , 500 MHz): ꢀ 10.22
3
(
7
s, 1H), 9.36 (s, 1H), 8.19 (d, 1H, J ¼ 8.3 Hz), 8.15 (d, 1H, J ¼ 8.3 Hz),
þ
.89–7.82 (m, 2H). Mass (FD): 158 (M ).
1
H NMR for Selected Compounds
ꢀ
[5]
Compound 1a: M.p. 246–247 C (lit. 247–248 C). H NMR (CDCl ,
ꢀ
1
3
3
1
00 MHz): ꢀ 12.52 (br s, 1H), 10.26 (s, 1H), 9.40 (s, 1H), 8.55 (br s, 1H),
.36 (s, 9H). H NMR reported in literature: ꢀ 12.51 (br, 1H), 10.28
1
[5]
(
s, 1H), 9.42 (s, 1H), 8.59 (br, 1H), 1.38 (s, 9H).
ꢀ
1
Compound 3a: M.p. 88–90 C (uncorrected). H NMR (CDCl3,
00 MHz): ꢀ 11.8 (s, 1H), 8.45 (d, 1H, J ¼ 8.3 Hz), 8.17 (bs, 1H), 7.95
5
(
C H N O : required C, 64.04; H, 6.84; N, 13.58. Found: C, 64.00; H,
d, 1H, J ¼ 7.4 Hz), 7.84 (t, 1H, J ¼ 7.9 Hz), 1.35 (s, 9H). Anal. Calcd for
11 14 2 2
6
.88; N, 13.32.
ꢀ
1
Compound 4a: M.p. 38–39 C. H NMR (CDCl , 500 MHz): ꢀ 10.16
3
(
s, 1H), 8.17 (d, 1H, J ¼ 7.6 Hz), 8.08 (t, 1H, J ¼ 7.6 Hz), 7.76 (d, 1H,
J ¼ 8.0 Hz), 2.66 (s, 3H).
Compound 5a: M.p. 218–219 C dec. (lit.
CDCl , 500 MHz): ꢀ 9.35 (d, 1H, J ¼ 1.0 Hz), 8.71 (d, 1H, J ¼ 2.3 Hz),
ꢀ
[7a]
ꢀ
1
219 C dec.). H NMR
(
3
8.49 (s, 1H).

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6
-Formylpterin
Compound 6a: M.p. 221–223 C (lit.
479
224–225 C). H NMR
ꢀ
[7b]
ꢀ
1
(
2
CDCl , 500 MHz): ꢀ 10.36 (s, 2H), 8.50 (d, 2H, J ¼ 8.2 Hz), 8.26 (d,
3
1
[7b]
H, J ¼ 8.3 Hz). H NMR (DMSO-d ) reported in literature : ꢀ 8.30
6
(
H-3, 8), 8.75 (H-4, 7), 8.25 (H-5,6), 10.45 (CHO).
ꢀ
[7c]
Compound 7a: M.p. 228–230 C (lit. 231–232 C). H NMR (CDCl ,
ꢀ
1
3
3
9
8
00 MHz): ꢀ 10.55 (s, 2H), 8.53 (d, 2H, J ¼ 6.0 Hz), 8.38 (d, 2H, J ¼
1
[7c]
.0 Hz), 7.95 (s, 2H). H NMR (DMSO-d ) reported in literature : ꢀ
6
.21 (d, H-3,6; 2H, J3,4 ¼ 8.0 Hz), 8.85 (d, H-4,5; 2H), 10.21 (s, CHO, 2H).
ACKNOWLEDGMENTS
We thank CSIR, Government of India for financial support and
Bose Institute, Kolkata for NMR facility. We also acknowledge the
help of Reshmi Mukherjee in our laboratory. We wish to thank
Professor Thomas Schrader of Philipps-Universitat, Marburg,
Germany for the mass spectrum. A. K. A. thanks CSIR, Government
of India for providing him a Senior Research fellowship.
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Received in the USA February 19, 2002