presence of the cyano acid.
Table 3 Conversion of miscellaneous dinitriles into acids
Conditions
When the aliphatic a,w-dinitrile chain is interrupted by vinyl
or aryl substituents, regiocontrol is efficiently observed in
almost all cases that we have examined except for
o-phenylenediacetonitrile (Table 2, entry 3). Although the
regiocontrol here (and in the case of aromatic dinitriles14) may
derive from a different basis, it is tempting to suggest that the
p-systems can also act as effective ligands for the iron when
chelation allows (Table 3). Also included in Table 3 is trans-
cyclohexane-1,4-diacetonitrile (entry 6) which shows total
regioselective hydrolysis, presumably by way of chelation of its
axial or twist–boat conformer.
In conclusion, we have defined the extent to which
regiocontrol can be expected in the hydrolysis of dinitriles
bearing O, S and to a limited extent N substituents, and
considered the control with p-functionalised dinitriles. The
application of these ideas to prochiral and chiral systems is now
being actively examined.
Conc./
Entry Substrate
mmol t/h
Product(s) and yields
CN
CN
CN
1
2
24
CO2H
80%
NC
2
R1
2
24
CN
R2
R1 = CN, R2 = CO2H 65%
R
1 = CO2H, R2 = CN 16%
R1
R2
CN
CN
3
3
24
R1 = R2 = CN 13%
We thank the BBSRC for a generous research grant that made
this work possible.
R
R
1 = CN, R2 = CO2H 11%
1 = R2 = CONH2 65%
Footnotes
CN
CN
* E-mail: otto.meth-cohn@sunderland.ac.uk
† We thank a referee for this suggestion.
4
5
3
3
30
30
CN
CO2H
67%
References
1 O. Meth-Cohn and M.-X. Wang, Tetrahedron Lett., 1995, 36, 9561;
J. Chem. Soc., Perkin 1, in the press.
2 Y. Asano, S. Ando, Y. Tani and H. Yamada, Agric. Biol. Chem., 1980,
44, 2497; H. Yamada, Y. Asano and Y. Tani, J. Ferment. Technol.,
1980, 58, 495.
CN
CO2H
NC
NC
69%
3 H. Yamada, Y. Asano and Y. Tani, Y. Asano, S. Ando, Y. Tani,
H. Yamada and T. Ueno, Agric. Biol. Chem., 1981, 45, 57.
4 C. Bengis-Garber and A. L. Gutman, Tetrahedron Lett., 1988, 29, 2589;
Appl. Microbiol. Biotechnol., 1989, 32, 11.
5 M. Kobayashi, N. Yanaka, T. Nagasawa and H. Yamada, Tetrahedron
1990, 46, 5587.
6 P. Ho¨nicke-Schmidt and M. P. Schneider, J. Chem. Soc., Chem.
Commun., 1990, 648.
7 M. A. Cohen, J. Sawden and N. J. Turner, Tetrahedron Lett., 1990, 31,
7223.
NC
NC
6
7
1.5 39
CO2H
CN
99%
67%
CN
CO2H
5
5
14
14
NC
NC
CN
CO2H
8
NC
NC
86%
8 H. Kakaye, N. Sakai, A. Sano, M. Yokoyama, T. Sugai and H. Ohta,
Chem. Lett., 1991, 1823.
9 J. A. Crosby, J. S. Parratt and N. J. Turner, Tetrahedron: Asymmetry,
1992, 3, 1547; A. Kerridge, J. S. Parratt, S. M. Roberts, F. Theil,
N. J. Turner and A. J. Willetts, Bioorg. Med. Chem. Lett., 1994, 2, 447;
S. Maddrell, N. J. Turner, A. Kerridge, A. J. Willetts and J. A. Crosby,
Tetrahedron Lett., 1996, 37, 6001.
cofactor present in such nitrile hydratases, pyrroloquinoline
quinone, as documented elsewhere.13 When a suitably placed
ligand atom is also present in the nitrile a bidentate complexa-
tion to the metal occurs, which interferes with the hydration of
the nitrile function. This ligand may be a suitably placed CO2H
function or a heteroatom. The glutaronitrile 1 (n = 3) bears a
d-oxygen ligand as does the ether 4 (n = 4, X = O). The C–S
bond is considerably longer than the C–O bond (1.81 and 1.43
Å respectively) and not surprisingly therefore a g placement
lends optimal regioselectivity. If this mechanism is correct, the
above ligands should behave as competitive inhibitors in the
hydrolysis of other easily hydrolysed nitriles.† This is indeed
found to be the case. Thus when the hydrolysis of benzonitrile
is followed (by HPLC) in the presence or absence of
NCCH2CH2CH2SCH2CH2CH2CO2H, we find that the rate of
benzonitrile disappearance is dramatically slower in the former
case. Thus after 5 min reaction, about 20% of unreacted
benzonitrile remained with no added cyano acid. In the presence
of the inhibitor almost 40% remained. After 10 min the figures
were ca. 2 and 25%. Furthermore the rate of decrease of amide
10 M. Yokoyama, T. Sugai and H. Ohta, Tetrahedron: Asymmetry, 1993, 4,
1081.
11 H. Nishise, M. Kurihara and Y. Tani, Agric. Biol. Chem., 1987, 51,
2613; Y. Tani, M. Kurihara, H. Nishise and K. Yamamoto, Agric. Biol.
Chem., 1989, 53, 3143; Y. Tani, M. Kurihara and H. Nishise, Agric.
Biol. Chem., 1989, 53, 3151; K. Yamamoto, Y. Ueno, K. Otsubo,
H. Yamane, K.-I. Komatsu and Y. Tani, J. Ferment. Bioeng., 1992, 73,
125.
12 J. L. Moreau, F. Bigey, S. Azza, A. Arnaud and P. Galzy, Biocatalysis,
1994, 10, 325 and references cited therein.
13 T. Nagasawa, H. Namba, K. Ryuno, K. Takeuchi and H. Yamada, Eur.
J. Biochem., 1987, 162, 691.
14 J. Crosby, J. Moilliet, J. S. Parratt and N. J. Turner, J. Chem. Soc.,
Perkin Trans. 1, 1994, 1679 and references cited therein; L. Mart´ınkova´,
P. Olsˆovsky´, I. Prepechalova´ and V. Kren, Biotechnol. Lett., 1995, 17,
1219.
Received in Cambridge, UK, 6th February 1997; Com.
7/00859G
1042
Chem. Commun., 1997