Efficient chemoselective reduction of 3-substituted coumarins utilizing ortho-phenylenediamine and benzaldehyde

Article abstract of DOI:10.3987/COM-01-9207

2-Phenylbenzimidazoline, generated in situ from ortho-phenylenediamine and benzaldehyde, is an effective reagent to achieve the chemoselective reduction of the styrenic double bond in 3-substituted coumarins, which takes place in high yield.

Full text of DOI:10.3987/COM-01-9207

HETEROCYCLES, Vol. 55, No. 7, 2001, pp. 1311 - 1314, Received, 21st March, 2001
EFFICIENT CHEMOSELECTIVE REDUCTION OF 3-SUBSTITUTED
COUMARINS
UTILIZING
ortho-PHENYLENEDIAMINE
AND
BENZALDEHYDE
Francesco Risitano,* Giovanni Grassi, Francesco Foti, and Cristina Bilardo
Dipartimento di Chimica Organica e Biologica, Università, Vill. S. Agata, I-98166 Messina,
Italy. E-mail: frisitan@isengard.unime.it
Abstract – 2-Phenylbenzimidazoline, generated in situ from ortho-phenylenediamine and
benzaldehyde, is an effective reagent to achieve the chemoselective reduction of the
styrenic double bond in 3-substituted coumarins, which takes place in high yield.
The reaction of ortho-phenylenediamine with electron deficient olefins in the presence of the appropriate
arylaldehyde is one of the best methods of chemoselective reduction of double C-C bonds conjugated
1
with electron withdrawing groups. This reaction occurs by way of in situ formation of 2-
2
phenylbenzimidazoline, which oxidises to benzimidazole and releases dihydrogen. The hydrogen transfer
mechanism seems to depend on the stereoelectronic properties of the substrate. For example, a two step
ionic process has been proposed in the reduction of nitro- and cyanoolefins or of an α,β-unsaturated
3
ester, while a SET mechanism has been hypothesised in the case of 4-arylmethylene isoxazol- or
4
pyrazol-5-ones. Nevertheless, the synthetic usefulness of this reaction has been demonstrated in both
cases.
We attempted to extend this efficient and mild reductive procedure to endocyclic double C-C bonds. In
this note we report the results obtained with coumarins (1) substituted with electron withdrawing groups
in 3 position.
5
o-Phenylenediamine (2) reacted with coumarins (1) in the presence of benzaldehyde and in the
6
conditions set up beforehand. The benzimidazoline (3), generated in ethanol or THF solution, reacted
7
8
with 1 giving the expected dihydro derivatives (4a-d) in high yield, and the 2-phenylbenzimidazole (5)
quantitatively (Scheme 1). Products deriving from a preferential attack of the diamine on the C-4 of the
9
lactones (1) were never isolated. In the case of 1e the coumarin substrate does not react, although the
benzimidazole (5) is recovered. This proves that benzimidazoline (4) was formed under the described
conditions.

The structure of the dihydrocumarins (4a, b, d) was assigned by comparing analytical and spectral data
1
0
with authentic samples prepared by other means. 4c was assigned by spectroscopic analogy with 4a, b,
d.
Considering the unequivocal intermediacy of benzimidazoline (3) as hydrogen donor , the way in which
the olefin site becomes saturated still needs to be clarified. The unsuccessful reaction of the coumarin (1e)
and the unobserved formation of reductive dimer by-products, exclude the two paths discussed above.
NH2
+
PhCHO
NH2
2
H
N
R
O
Ph
+
O
N
H
H
1
3
R = -CN
1
e
+
5
R
O
N
Ph
+
N
H
O
5
4
R
-COMe
-COPh
-CO Me
-CO Et
-CN
2
2
a
b
c
d
e
Thus, it may be assumed that the hydrogen transfer to the multiple bond of the 3-substituted lactones (1)
could take place through A.
In A, as a consequence of the hydrogen bond between the carbonyl oxygen at the 3-position and one of
the NH groups, benzimidazoline and coumarin are in such a position as to reasonably allow hydrogen
transfer to occur.
Coumarins (1) (R = H and R = p-NO C H ), as well as 1e, did not undergo any reduction under the same
2
6
4

reaction conditions and could be recovered at the end of the reaction together with benzimidazole (5).
Association such as A was prevented in the case of 3-cyanocoumarin (1e) shown in B. The hydrogen
transfer can not take place from this configuration. In addition, the conformation of benzimidazoline
would make the nitrogen lone pairs in antiperiplanar position to the Csp3-H bond. This appears to
contribute to weaken the C-H bond, which generates a hydride ion.
H
N
Ph
N
H
N
Ph
H
H
N
H
H
N
O
O
O
O
O
A
B
In conclusion, we have reported a new efficient method for the chemoselective reduction of coumarins.
1
1
The present method is superior to other more sophisticated methods in that it offers the ready access to
the reducing agents, operational simplicity, mild conditions, and high yields of dihydro coumarine
derivatives.
REFERENCES AND NOTES
1
2
3
. a) F. Risitano, G. Grassi, F. Caruso, and F. Foti, Tetrahedron, 1996, 52, 1443 and references cited
therein; b) G. Bruno, G. Grassi, F. Nicolò, F. Risitano, and R. Scopelliti, Acta Cryst., 1996, 3121.
. D. M. Smith in Dihydrobenzimidazoles, Benzimidazolones, Benzimidazolethiones, and Related
Compunds in Chemistry; John Wiley & Sons, N.Y., 1981, pp. 331-334.
. a) H. Chikashita, S. Nishida, M. Miyazaki, Y. Morita, and K. Itoh, Synth. Commun., 1983, 13, 1033;
b) H. Chikashita, S. Nishida, M. Miyazaki, Y. Morita, and K. Itoh, Bull. Chem. Soc. Jpn., 1987, 60,
737 and references cited therein.
4
. The proposed radical mechanism for the 4-arylmethyleneazolones is the only one that can explain the
formation of products derived from a reductive dimerisation and the non-heterocyclic ring opening
followed by rearrangements (ref. 1). An example is the reduction, under classic conditions, of
arylmethyleneisoxazol-5-ones: G. Shaw, J. Chem. Soc., 1950, 720.

5
6
7
. R. O. Clinton and S. C. Laskowski, J. Chem. Soc., 1949, 71, 3602.
. F. Risitano, G. Grassi, and F. Foti, Tetrahedron Lett., 1983, 5893.
. General procedure: An EtOH (or THF) solution of diamine (2) (432 mg, 4.0 mmol) was added
dropwise over 20 min to a refluxing mixture of 1 (4.0 mmol) and benzaldehyde (655 mg, 5.5 mmol)
in EtOH (50 mL). Stirring was continued for a further 0.5 h and then the reaction mixture was
evapored to give an oil residue which was neutralised with HCl 10% (30 mL). The acidic aqueous
suspension was then extracted with ether (3x30 mL) and the combined ether extracts were washed
with water (70 mL) and dried on sodium sulfate. Filtration followed from evaporation of the filtrate
solvent gave an oil which was crystallized from ethanol or chromatographed on a silica gel (with
chloroform as eluent) to yield the dihydro derivatives (4). The acidic solution with benzimidazole
hydrochloride in suspension was made alkaline with 10% sodium hydroxide to give benzimidazole
7
(
5). The following products have been isolated: 4a from coumarin (1a) in 85% yield, mp 75°C (lit.,
7
mp 72-85°C); 4b from 1b in 92% yield, mp 99°C (lit., mp 102°C); 4c from 1c in 85% yield, mp
9
1°C. Anal. Calcd for C H O : C, 64.07; H, 4.89. Found C, 63.99; H, 4.85. IR (Nujol): ν =1772
11 10 4 max
-
1 1
and 1738 cm . H NMR (CDCl ): δ= 4.05 (3H, s, OCH ), 3.19 (1H, dd, J = 6.5, 16.1 Hz), 3.45 (1H,
3
3
dd, J = 8.9, 16.1 Hz), 3.79 (1H, dd, J = 6.5, 8.9 Hz), 6.8-7.5 (4H, m). 4d from 1d in 81% yield, mp
7
5
1°C (lit., mp 51-52.5°C). From 1e and 1 (R= H or 4-nitrophenyl) no corresponding derivative (4)
was obtained, but the starting coumarin and benzimidazole (5).
. A. Ladenburg, Ber., 1877, 10, 1123.
8
9
1
1
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