3
580
C. I. Chiriac et al. / Tetrahedron Letters 44 (2003) 3579–3580
Table 1. Cinnamic acids obtained by direct synthesis in the presence of sodium borohydride
Cinnamic acidsa
Yieldb (%)
Reaction time (h)
M.p. (°C)
c
Literature m.p. (°C)
7
III a
III b
III c
III d
III e
III f
III g
III h
74
66
83
86
81
59
72
77
10
12
9
176–177
131–133
248–250
285–286
195–197
173–175
105–107
195–197
175–177
132–133
249–250
284–286
196–197
173–175
106–107
196–197
8
7
9
9
1
8
9
9
0
10
12
10
10
a
The cinnamic acids obtained were identified by comparison of their m.p. and IR spectra with authentic samples.
Yields calculated based on the aromatic aldehydes I employed.
After recrystallization.
b
c
+
−
NaBH (1 mole)+CH COOH (1 mole)Na B
to the classical Perkin synthesis. Without the sodium
borohydride, the synthesis is not possible.
4
3
H OOCCH +H
Ref. 4
3
3
2
+
−
NaBH (1 mole)+CH COOH (3 mole)Na B
4
3
H(OOCCH ) +3H
Ref. 5
3
3
2
References
+
−
NaBH (1 mole)+CH COOH (4 mole)Na B
1. (a) Johnson, J. R. Org. React. 1942, 1, 210; (b) Johnson,
J. R. Org. Syn. Coll. 1955, 3, 426.
4
3
(
OOCCH ) +4H
Ref. 6
3
4
2
2
. Kalnin, P. Helv. Chim. Acta 1928, 11, 977.
We found that this last compound 3, prepared in situ in
acetic acid solution, can react with aromatic aldehydes
to give the corresponding cinnamic acids.
3. Crawford, M.; Little, W. T. J. Chem. Soc. 1959, 722.
4. Reetz, T. J. Am. Chem. Soc. 1960, 82, 5039.
5. Hutchins, R. O. J. Org. Chem. 1978, 43, 2301.
6
. Markini, P. J. Org. Chem. 1975, 40, 3455.
By stepwise investigations, we established that aromatic
aldehydes I can react with aliphatic carboxylic acids II
in the presence of sodium borohydride, in the mole ratio
7. Cleland, G. H. J. Org. Chem. 1961, 26, 3362.
8. Fedorov, B. S. Prom. Org. Sin. Akad. Nauk SSSR 1967,
173 (Chem. Abstr. 1968, 68, 77903h).
1
: excess: 1.33, resulting in cinnamic acids III, as presented
9. Urushibara, Y.; Hirota, M. Nippon Kagaku Zasshi 1961,
82, 351 (Chem. Abstr. 1962, 56, 10025g).
in Scheme 1.
10. Zimmerman, H. J. Am. Chem. Soc. 1959, 81, 2091.
Using a mole ratio between the aldehyde I and NaBH4
11. General procedure for the synthesis of cinnamic acids: In
a 100 mL three-necked Claisen flask fitted with a mechanical
stirrer, 0.14 mole (excess) of aliphatic carboxylic acid II was
added. Then, 1 g (0.0266 mole) of sodium borohydride was
added slowly in small portions, under stirring and cooling
with ice, in order to maintain the temperature in the flask
at 20–30°C. Then, the solution obtained was stirred for 1
h at room temperature, and then for 1 h at 90–100°C. To
this solution, at 70–90°C, 0.02 mole of aromatic aldehyde
I was added and then 2mL of NMP as solvent. The solution
obtained was stirred for 2–3 min. The mechanical stirrer
was replaced with a condenser and the excess of compound
II was removed by distillation, until the temperature in the
flask increased to 185–187°C. Then, the distillation set was
replaced with an air-cooled reflux condenser 30 cm long and
of 1:1.33, good yields for this reaction were obtained.
Without a suitable solvent, this reaction is difficult to
perform. We tested many solvents, such as DMSO, DMF,
N-methyl-2-pyrrolidinone (NMP), HMPTA etc. From
these solvents, we selected NMP because it is a good
solvent for our products, is stable under the reaction
conditions and has a high boiling point (202°C).
The synthesis necessitates high temperatures (reflux at
1
80–190°C), during 9–12 h (Table 1). At lower temper-
atures, the yields decrease. For example, the yield for
product IIIa decreased to 45–48% when the reaction was
performed at 145–150°C, for 6 h.
2.9 cm in diameter, which was extended with a water-cooled
Ascan be seen in Table 1, cinnamicacids III wereobtained
in yields which ranged from 59 to 86% depending on the
reaction conditions and structure of the aldehyde. The
cinnamic acid IIIf was obtained with the lowest yield.
Cinnamic acids with electron-withdrawing groups were
reflux condenser. This solution was heated under reflux, at
185–190°C, for 9–12 h (see Table 1). At the end of the
reaction, the final solution was treated with 70–80 mL water
and then with NaOH solution 20%, to pH=9–10. From
this solution, the unreacted aromatic aldehyde I was
distilled with water under vacuum (30–40 mm Hg), until
the distillate was no longer cloudy. The solution was diluted
with water until a volume of 80–90 mL was obtained which
was then filtered at 30–40°C. The filtrate was treated with
HCl solution 15–20%, until pH=1–2, when cinnamic acid
III precipitated. After 2–3 h of stirring under cooling with
ice, the final product III obtained was filtered, washed with
15–20 mL cold water and dried. Yields ranged from 59 to
86% (Table 1).
1
1
obtained in good yields.
The detailed mechanism of this reaction will be discussed
in a separate communication.
In conclusion, we have found a new synthesis for the direct
preparation of cinnamic acids from aromatic aldehydes
and aliphatic carboxylic acids in the presence of sodium
borohydride. This method is a very effective alternative
Chiriac, Constantin I.
