5724 J . Org. Chem., Vol. 64, No. 15, 1999
Notes
1H NMR (300 MHz, DMSO-d6) δ 7.86 (d, J ) 8.2 Hz, 2H), 7.32
(d, J ) 8.2 Hz, 2H), 5.33 (d, J ) 5.7 Hz, 1H), 3.82-3.87 (m, 1H),
3.81 (s, 3H), 2.58-2.67 (m, 2H), 1.36-1.84 (m, 4H); 13C NMR
(DMSO-d6) δ 166.23, 148.32, 129.17, 128.69, 127.10, 82.69, 51.94,
35.06, 31.25, 27.16.
Eth yl 2-For m yl-1-cyclopr opan ecar boxylate Bisu lfite Ad-
d u ct (7-A). 1H NMR (DMSO-d6) δ 5.58 (d, J ) 5.9 Hz, 1H), 3.93-
4.11 (m, 2H), 3.50-3.57 (m, 1H), 1.59-1.68 (m, 2H), 1.16 (t, J
) 7.0 Hz, 3H), 0.89-0.98 (m, 2H); 13C NMR (DMSO-d6) δ 173.47,
83.04, 59.75, 23.87, 16.80, 14.07, 12.65.
1
Hyd r ocin n a m a ld eh yd e Bisu lfite Ad d u ct (8-A). H NMR
(DMSO-d6) δ 7.12-7.31 (m, 5H), 5.37 (br, 1H), 3.82 (d, J ) 9.2
Hz, 1H), 2.70-2.81, m, 1H), 2.54-2.66 (m, 1H), 1.97-2.97 (m,
1H), 1.68-1.82 (m, 1H); 13C NMR (DMSO-d6) δ 142.21, 128.32,
128.15, 125.50, 33.71, 31.47.
P h en yla ceta ld eh yd e Bisu lfite Ad d u ct (9-A). Mp > 300
1
(dec); H NMR (DMSO-d6) δ 7.12-7.30 (m, 5H), 5.42 (br, 1H),
In summary, a new method for cleavage of bisulfite
adducts to the parent aldehydes has been developed. The
new method is nonaqueous, which greatly expands the
list of aldehydes which are compatible. Utility has been
demonstrated by the purification of 1 generated by the
LaRock coupling procedure and by the purification of
commerically available aldehydes 7-10.
4.02 (dd, J ) 4.0, 11.0 Hz, 1H), 3.14 (dd, J ) 2.0, 13.8 Hz, 1H),
2.70 (d, J ) 10.5 Hz, 1H), 2.65 (d, J ) 10.5 Hz, 1H); 13C NMR
(DMSO-d6) δ 139.7, 129.21, 127.88, 125.64, 84.06, 38.06. Αnal.
Calcd for C8H9O4SNa (224.01): C, 42.86; H, 4.05.
2,2-Dich lor oh exa n a l Bisu lfite Ad d u ct (10-A). 1H NMR
(DMSO-d6) 6.22 (d, J ) 6.9 Hz, 1H), 4.28 (d, J ) 6.9 Hz, 1H),
2.42-2.51 (m, 2H), 1.53-1.71 (m, 2H), 1.24-1.38 (m, 2H), 0.89
(t, J ) 7.6 Hz, 3H); 13C NMR (DMSO-d6) δ 97.67, 89.03, 42.59,
27.44, 22.21, 14.30.
Gen er a l P r oced u r e for Regen er a tion of Ald eh yd es fr om
Bisu lfite Ad d u cts. Regeneration of ethyl 2-formyl-1-cyclopro-
panecarboxylate 7 is representative. Ethyl 2-formyl-1-cyclopro-
panecarboxylate bisulfite adduct 7-A (1.00 g, 406 mmol), CD3CN
(8.0 mL), anisole or pyrazine(as an internal standard for
analysis), and TMS-Cl (1.22 g, 11.2 mmol) were combined and
Exp er im en ta l Section
Analytical instrumentation was as previously described.8
Ethyl 2-formyl-1-cyclopropanecarboxylate 7 (Aldrich), hydrocin-
namaldehyde 8 (Aldrich), phenylacetaldehyde 9 (Aldrich), and
2,2-dichlorohexanal (Acros), all reagents, and all solvents were
used as obtained. All reactions were run under a nitrogen
atmosphere.
Gen er a l P r oced u r e for Bisu lfite Ad d u ct F or m a tion . The
synthesis of ethyl 2-formyl-1-cyclopropanecarboxylate bisulfite
adduct 7-A is representative.9 Aldehyde 7 (2.0 g, 14.1 mmol),
sodium bisulfite (1.31.g, 12.6 mmol), ethyl acetate (10 mL),
ethanol (6 mL), and water (2 mL) were combined and heated to
40 °C for 2.2 h. The mixture was allowed to cool to ambient
temperature, filtered, washed with ethanol (10 mL), and dried
to give bisulfite adduct 7-A as colorless crystals (2.11 g, 8.6
mmol, 61%).
1
heated to 40 °C. After 2.2, h H NMR analysis of filtered aliquots
indicated a quantitative in situ yield of 7. The mixture was
allowed to cool to ambient temperature. Ethyl acetate (6.0 mL)
was added. The mixture was washed with water and brine. The
organic layer was dried over Na2SO4, filtered, and concentrated
to yield 7 (0.511 g, 3.6 mmol, 98% (corrected for sampling
losses)).
Ack n ow led gm en t . We thank Charles Barnett,
Tracey Blom, J ason Cronin, and Michael Kobierski for
their advice and support. Michael Fogarty and Paula
Gillespie are thanked for the development of the GC
assay conditions. Professors Marvin Miller and William
Roush are thanked for their consultation.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for bisulfite adducts 5, and 7A through 10A. This
material is available free of charge via the Internet at
http://pubs.acs.org.
4-(4-Ca r bom eth oxyp h en yl)bu ta n a l Bisu lfite Ad d u ct (5).
A mixture of compounds 1-4 in DMF was prepared as previously
described.4 Addition of ethyl acetate, and filtration, followed by
aqueous and brine washes, yielded a solution in ethyl acetate
ready for bisulfite adduct formation by the standard method.
(8) Kjell, D. P.; Slattery, B. J . Nucleosides Nucleotides 1997, 16,
469-474.
(9) Kjell, D. P.; Slattery, B. J .; Barnett, C. J . EU Patent Appl.
905128, 1999.
J O990543V