P. J. Gerrits et al. / Tetrahedron 57 -2001) 8691±8698
8697
2
7
containing 3 ml of a 3.42£10 M mixture of the cyano-
benzaldehyde were added to the ¯ask. After stirring for
three days a conversion of 90% into the cyanohydrin was
reached. Crude cyanohydrin was obtained as oil, 0.12 g
hydrin in hexane.
8
4.3.1. 2-Hydroxybenzeneacetonitrile /entry 1, Table 3).
To a thermostatically cooled &58C) double-walled reaction
yield. HPLC: OJ-column, eluent H/I/HAc87:13:0.1, l
1
aldehyde 278 nm). H
230 nm, l
210 and 231 &l
max
max
vessel, 60 ml of a 0.1 M phosphate/citrate buffers &pH 5.5,
7
NMR &acetone-d ): d4.76&s, 2H, C H OH); 5.65 &s, 1H,
6
2
.0, 8.0, 9.0) were added. Meanwhile 10 g of NaCN was
CHCN); 6.87 &d, 1H, J8.2 Hz, H-arom); 7.26&dd, 1H,
1
dissolved in 100 ml of cold water. The pH of this solution
was adjusted to 5.5 by addition of citric acid. CAUTION:
Formation of toxic hydrogen cyanide! The hydrogen
cyanide solution was extracted with MTBE &3£40 ml).
The combined MTBE layers were added to the reaction
vessel. Freshly distilled benzaldehyde &26mmol) was
added to the solution to start the reaction. After 5 h the
reaction was converted for 99.8%. After separation of the
J2.1, 8.2 Hz, H-arom). HRMS &EI): M , found
179.1720. C H NO requires 179.1727.
9
9
3
4.3.5. 3E-2-Hydroxy-4-phenylbutenenitrile /entry 5,
Table 3).
7
,26
Prepared as described above for 2-hydroxyꢀ
benzeneacetonitrile using 40 mmol of cinnamaldehyde.
After two days a conversion of 98% was reached. Crude
cyanohydrin was obtained as a clear yellow solid, yield
97% cyanohydrin. The crude cyanohydrin was separated
two layers, the organic layer was dried &MgSO ) and the
4
solvent evaporated. Pure racemic mandelonitrile was
obtained as a clear oil which solidi®ed at 58C. HPLC, eluent
from the aldehyde by crystallizing in CH Cl /n-hexane, to
2 2
give pure cyanohydrin as light yellow colored crystals. Mp
788C. HPLC: eluent H/I/HAc87:13:0.1, l 261.5 nm,
H/I/HAc97:3:0.1,
l
220 nm. lmax220 nm &lmax
1
1
aldehyde250 nm). H NMR &CDCl ): d3.15 &br, 1H,
l
&CDCl
max253 nm &lmax aldehyde284 nm).
H
NMR
3
1
3
OH), 5.52 &s, 1H, CHOH), 7.49 &m, 5H, H-arom);
C
NMR &CDCl )U63.22 &COH), 119.16 &CN), 126.70,
3
): d3.96&br, 1H, OH), 5.16&d, 1H, J6.2 Hz,
CHCN), 6.27 &dd, 1H, J6.2, 15.9 Hz, vCHCHCN), 6.89
3
1
3
1
29.12 &C-arom), 129.71 &Cpara), 135.14 &Cipso).
&d, 1H, J15.9 Hz, CHvCH), 7.39 &m, 5H H-arom);
C
NMR &CDCl )U61.60 &CHOH) 118.30 &CN), 122.00
3
4
2
.3.2. 2-Hydroxy-2-/4-hydroxyphenyl)-acetonitrile /entry
Prepared as described above for 2-hydroꢀ
&C-arom), 127.00 &CHvCH), 128.70 &C-arom), 128.90
&CHvCH), 134.60 &Cipso), 135.00 &C-arom).
2
6,27
, Table 3).
xybenzeneacetonitrile using 24.6mmol of 4-hydroxyben-
zaldehyde. After 24 h the reaction was 91% converted
into cyanohydrin. Cyanohydrin was obtained as a light
pink solid and could be separated from the aldehyde by
crystallization in dichloromethane/petroleum-ether 40±60
to give pure cyanohydrin as light pink colored crystals.
4.3.6. 2-Hydroxy-3E,5E-heptadienenitrile and 2-hydroxy-
3E,5Z-heptadienenitrile /entry 6, Table 3).
9
b,26
Prepared
as described above for 2-hydroxybenzeneacetonitrile using
57.2 mmol of 2,4-hexadienal, 15 g of NaCN in 120 ml of
cold water and 60 ml of a phosphate/citrate buffer &pH 7).
After 24 h, a conversion of 97% was observed. The cyano-
hydrin was obtained as a yellow solid. The reaction was
followed and no additional isomerization was observed
during the reaction. HPLC: eluent H/I/HAc97:3:0.1, l
HPLC: OJ-column, eluent H/I/HAc87:13:0.1, l 230 nm.
1
aldehyde 218 and 270 nm). H NMR
l
230 nm &l
max
max
&
acetone-d ): d5.66 &s, 1H, CHCN), 6.91 &d, 2H, J
6
1
3
8
NMR &acetone-d )U62.28 &CHOH), 115.43 &C-arom),
.78 Hz, H-arom), 7.41 &d, 2H, J8.78 Hz, H-arom);
C
1
231 nm, lmax 232 nm, &lmax aldehyde 260 nm). H NMR
6
1
&
19.20 &CN), 128.10 &C-arom), 157.97 &Cipso), 166.58
Cipso).
&CDCl
OH), 5.01 &d, 1H, CH±CN, J5.9 Hz), 5.63 &dd, 1H,
vCHCHCN, J15.2, 6.2 Hz), 5.91 &dd, 1H, MeCHvCH,
3
): d1.80 &d, 3H, CH , J5.6Hz), 3.05 &br, 1H,
3
1
3
4
3
.3.3. 2-Hydroxy-2-/2-hydroxyphenyl)-acetonitrile /entry
, Table 3). Prepared as described above for 2-hydroxyꢀ
J15, 7 Hz), 6.10 &dd, 1H, MeCHvCH, J15, 0.5 Hz); C
), 61.55 &CHOH), 118.35 &CN),
3 3
2
6
NMR &CDCl
122.61 &CH
)U18.10 &CH
CvC), 129.14 &CvCHCHCN), 134.66
3
benzeneacetonitrile using 47.5 mmol of salicylaldehyde and
0 ml phosphate/citrate buffer &pH 7.5). After 24 h the
6
&CH
CvC) 135.63 &vCHCHCN).
3
reaction was 99.8% converted into the cyanohydrin. Pure
cyanohydrin was obtained as a yellow oil. HPLC: OJ-
column, eluent H/I/HAc80:20:0.1, l 220 nm. l
215
aldehyde 220 nm). H NMR &acetone-
Acknowledgements
max
1
and 255 nm &l
max
d ): d5.87 &s, 1H, CHCN), 6.94 &m, 2H, H-arom), 7.26
This work was carried out as part of the Innovation Oriented
Research Program on Catalysis &IOP-katalyse, No. IKA
94026a) funded by The Netherlands Ministry of Economic
Affairs. The authors wish to thank Dr M. Beishuizen
&University of Leiden) for helpful ideas and assistance.
6
1
m, 1H, H-arom), 7.55 &m, 1H, H-arom); C NMR &ace-
3
&
tone-d )U56.33 &CHOH), 113.73 &C-arom), 117.83 &CN),
6
1
1
18.19 &C-arom), 121.34 &Cipso), 125.50, 128.56&C-arom),
52.33 &Cmeta).
4
.3.4. a-Hydroxy-/4-hydroxy-3-hydroxymethylphenyl)-
2
6
acetonitrile /entry 4, Table 3). To a round bottom
ask, 5 ml of a 0.1 M phosphate/citrate buffer &pH 6.8)
were added. Meanwhile 1 g of NaCN was dissolved in
7 ml of cold water. The pH of this solution was adjusted
References
¯
1. &a) Marcus, J. Enantioselective Bio-Organic Synthesis and
Application of Chiral Cyanohydrins, PhD Thesis, University
of Leiden, 2001. &b) Effenberger, F. Angew. Chem., Int. Ed.
Engl. 1994, 33, 1555±1564. &c) Gregory, R. J. H. Biocatalytic
Preparation and Chemistry of Some Novel Cyanohydrin
Systems, PhD Thesis, University of Liverpool, 1998.
1
to 5.5 by addition of citric acid. CAUTION: Formation of
toxic hydrogen cyanide! The hydrogen cyanide solution was
extracted with MTBE &1£40 ml). 23 ml hydrogen cyanation
extract and 0.66 mmol of 4-hydroxy-3-hydroxymethyl-