Org. Synth. 1981, 60, 49
DOI: 10.15227/orgsyn.060.0049
N-(2,4-DIFORMYL-5-HYDROXYPHENYL)ACETAMIDE
[Acetamide, N-(2,4-diformyl-5-hydroxyphenyl)-]
Submitted by Jürgen Hocker and Henning Giesecke
1.
Checked by G. Saucy, Harvey Gurien, and Gerald Kaplan.
1. Procedure
A. N-[2,4-Bis(1,3-diphenylimidazolidin-2-yl)-5-hydroxyphenyl]acetamide. A 500-mL, three-necked flask equipped with nitrogen inlet, mechanical stirrer, reflux condenser, and thermometer is charged with 88.8 g (0.2 mol) of 1,1',3,3'-tetraphenyl-2,2'-biimidazolidinylidene (Note 1) and 30.2 g (0.2 mol) of 3-acetamidophenol (Note 2). The system is flushed with and maintained under nitrogen, and 100 mL of chlorobenzene (Note 3) is added. The suspension is stirred at 100°C for 6 hr (Note 4). 2-Propanol (250 mL) is added to the hot mixture, which is then allowed to cool to room temperature. A pale-yellow solid precipitates which is filtered and washed with 200 mL of 2-propanol. Drying in vacuum affords 84.6–93.2 g (71–78%) of N-[2,4-bis(1,3-diphenylimidazolidin-2-yl)-5-hydroxyphenyl]acetamide, mp 254–256°C (Note 5).
B. N-(2,4-Diformyl-5-hydroxyphenyl)acetamide. A suspension of 95 g of the phenol (prepared as described under Section A) (Note 6) in 1 L of aqueous 10% hydrochloric acid is stirred for 2 hr at room temperature. The colorless solid (Note 7) is filtered by suction and twice suspended in water at 40°C. Final filtration is followed with a water wash (1 L, 40°C), and the solid is sucked down on the filter. Crystallization from 800 mL of acetonitrile affords 21.8–22.3 g (66–67.5%) of N-(2,4-diformyl-5-hydroxyphenyl)acetamide, mp 215–217°C (Note 8).
2. Notes
2.
The checkers purchased
3-acetamidophenol from Aldrich Chemical Company, Inc.3.
The
chlorobenzene was dried by azeotropic distillation.
4.
The submitters checked the reaction progress by adding
chloroform to an aliquot of the reaction mixture and observing it under long-wavelength UV light (350 mm). A bright fluorescence indicated incomplete reaction. The checkers found that further heating did not eliminate the fluorescence or improve the yield. Adding
1-g quantities of the phenol resulted in quenching of the fluorescence but a lower yield.
5.
The product showed the following spectroscopic properties:
1H NMR (d
7-DMF) δ: 1.92 (s, CH
3), 3.5–4.1 (m, 8 H, NCH
2), 6.05 (s, 1 H), 6.36 (s, 1 H), 6.5–7.5 (m, 23 H), 9.13 (s, 1 H).
6.
The
phenol should be ground in a
mortar to eliminate lumps.
7.
The checkers always obtained pale-yellow material.
8.
The product had the following spectroscopic properties: IR (KBr) cm
−1: 1659, 1644, 1620;
1H NMR (d
7-DMF) δ: 2.24 (s, CH
3), 8.22 (s, 1 H), 8.24 (d,
J < 1 Hz, 1 H), 9.87 (d,
J < 1 Hz, 1 H), 10.16 (s, 1 H), 11.35, 12.05 (2s, OH, NH).
3. Discussion
The reaction of
1,1',3,3'-tetraphenyl-2,2'-biimidazolidinylidene with phenols illustrated in this procedure is a general method for the preparation of phenolaldehydes.
2 Table I gives the aldehydes that have been prepared by conditions similar to those described here.
Nitrogen-containing heterocyclic compounds such as indoles and imidazoles are also formylated by the electron-rich olefin. 3-Methylimidazole-5-carboxaldehyde can be prepared from 2-methylimidazole (yield 83%) and 2-phenylindole-3-carboxaldehyde from 2-phenylindole (yield 64%).
TABLE I
ALDEHYDES FROM PHENOLS AND 1,1',3,3'-TETRAPHENYL-2,2'-BIIMIDAZOLIDINYLIDENE
|
|
|
Yield (%)
|
|
Aldehyde
|
Imidazolidin-2-yl-phenol
|
Hydrolysis
|
|
|
4-Hydroxybenzaldehyde
|
55
|
88
|
|
4-Hydroxy-3,5-dimethylbenzaldehyde
|
58
|
80
|
|
3-Cyclohexyl-5-methylsalicyladehyde
|
43
|
80
|
|
4-Dimethylamino-5-methylsalicylaldehyde
|
65
|
54
|
|
4-Dimethylaminosalicylaldehyde
|
52
|
90
|
|
Resorcinol-2,4,6-tricarboxaldehyde
|
43
|
96
|
|
4-Hydroxy-5-methoxyisophthalaldehyde
|
55
|
81
|
|
4-Hydroxy-6-methoxyisophthalaldehyde
|
57
|
87
|
|
Pyrogallol-4,6-dicarboxaldehyde
|
82
|
50
|
|
8-Hydroxyquinoline-7-carboxaldehyde
|
76
|
69
|
|
The formylation of phenols with the electron-rich olefin to give imidazolidin-2-yl-phenols is very selective and avoids mixtures of o- and p-isomers, which are frequently obtained by methods commonly employed for the synthesis of phenolaldehydes. Para substitution of the cyclic aminal group in the phenol is preferred. If the p-position is blocked or sterically hindered, the reaction proceeds via the ortho-aminals to salicylaldehydes. Incorporation of more than one aldehyde group in the benzene nucleus is often achieved with hydroxy- and aminophenols.
Reaction of phenols bearing strong electron-withdrawing substituents such as dichlorophenols and nitrophenols with 1,1',3,3'-tetraphenyl-2,2'-biimidazolidinylidene results in poor yields. Oxidation of the electron-rich olefin by nitro compounds is also possible.
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
indoles
imidazoles
3-Cyclohexyl-5-methylsalicyladehyde
imidazolidin-2-yl-phenols
salicylaldehydes
dichlorophenols
nitrophenols
hydrochloric acid (7647-01-0)
acetonitrile (75-05-8)
chloroform (67-66-3)
phenol (108-95-2)
nitrogen (7727-37-9)
chlorobenzene (108-90-7)
2-propanol (67-63-0)
2-Phenylindole (948-65-2)
3-acetamidophenol (621-42-1)
3-Methylimidazole-5-carboxaldehyde
4-Hydroxybenzaldehyde (123-08-0)
4-Hydroxy-3,5-dimethylbenzaldehyde (2233-18-3)
4-Dimethylamino-5-methylsalicylaldehyde
4-Dimethylaminosalicylaldehyde
Resorcinol-2,4,6-tricarboxaldehyde
4-Hydroxy-5-methoxyisophthalaldehyde
4-Hydroxy-6-methoxyisophthalaldehyde
Pyrogallol-4,6-dicarboxaldehyde
8-Hydroxyquinoline-7-carboxaldehyde
2-methylimidazole (693-98-1)
2-phenylindole-3-carboxaldehyde (25365-71-3)
N-(2,4-Diformyl-5-hydroxyphenyl)acetamide,
Acetamide, N-(2,4-diformyl-5-hydroxyphenyl)- (67149-23-9)
N-[2,4-Bis(1,3-diphenylimidazolidin-2-yl)-5-hydroxyphenyl]acetamide (67149-22-8)
1,1',3,3'-tetraphenyl-2,2'-biimidazolidinylidene (2179-89-7)
Imidazolidin-2-yl-phenol
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