Organic Syntheses, CV 7, 162
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).
2. Notes
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.
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
Compounds Referenced (Chemical Abstracts 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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