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Ytterbium (III) triflate catalyzed Biginelli reactions; methyl 4-(4-bromophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate; methyl 4-(4-methoxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate; and, methyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate

SyntheticPage 826
DOI: 10.1039/SP826
Submitted Jun 15, 2017, published Jun 21, 2017
Steven M. Kennedy (Steven.Kennedy@millersville.edu), Lauren Ostopowicz (laostopo@millersville.edu), Raquel Hernández (rahernan@millersville.edu), Peter J. Sitarik (pjsitari@millersville.edu)
A contribution from Kennedy Group, Millersville University


			Reaction Scheme: <IMG src="/images/empty.gif">Ytterbium (III) triflate catalyzed Biginelli reactions<IMG src="/images/empty.gif">

Chemicals Used

Ytterbium(III) triflate hydrate (99.9%, Acros)
Methyl acetoacetate (99%, Acros)
Urea (99%, Fisher Chemical)
Benzaldehyde (98%, TCI America)
4-Bromobenzaldehyde (99%, Acros)
p-Anisaldehyde (99%, TCI America)
Acetic acid, Glacial (Certified ACS, Fisher)

Procedure

Urea (0.48 g, 8.0 mmol) and ytterbium(III) triflate (0.26 g, 0.4 mmol) were added to a 1 dram (3.7 mL) glass reaction vial. Then, the 3:1 acetic acid:water solvent mixture (2 mL) was added to the vial; next, the methyl acetoacetate (0.86 mL, 8 mmol) was added, followed by the aldehyde (4 mmol). The stirred solution was heated for 15 minutes at 95 °C and developed an intense yellow colour. The reaction vial was cooled to room temperature; and, its contents were poured into a 25 mL beaker with 2 mL of ice and 5 mL of deionized water to fully precipitate the product. The solid was collected by vacuum filtration using a hirsch filter. The solid was washed with cold water (5 mL), then with toluene (5 mL); removal of the residual solvent by rotary evaporation provided the product in reasonable purity.


Author's Comments

These reactions were carried out open to air and in a fume hood. Prior to heating, the reaction vials were capped with a septa; then, the septa was vented with an 18 gauge disposable needle, before placing the reaction vial in the 95 °C hot oil bath. Due to the short reaction time, a reflux condenser was not employed. The lead reference (Damkaci and Szymaniak) contains detailed supplimentary information (http://pubs.acs.org/doi/abs/10.1021/ed400390k). The additonal reference (Aridoss and Jeong) was used for literature melting points.

Data

Methyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate (1): white solid (0.80 g, 81% yield) M.p. 212-213 °C (lit. 212-214 °C).

1H NMR (400 MHz, DMSO-d6): δ 2.23 (s, 3H), 3.51 (s, 3H), 5.12 (s, 1H), 7.20-7.32 (m, 5H), 7.76 (s, 1H), 9.23 (s, 1H).
13C NMR (100 MHz, DMSO-d6): δ  18.29, 51.27, 54.21, 99.40, 126.61, 127.76, 128.92, 145.10, 149.15, 152.63, 166.28.


Methyl 4-(4-bromophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (2):
pale yellow powder (0.74 g, 57%) M.p. 221-222 °C (lit. 218-220 °C).




1
H NMR
(400 MHz, DMSO-d6): δ 2.23 (s, 3H), 3.51 (s, 3H), 5.10 (s, 1H), 7.16 (d, 2H), 7.51 (d, 2H), 7.79 (s, 1H), 9.28 (s, 1H).
13
C NMR
(100 MHz, DMSO-d6): δ  18.31, 51.32, 53.75, 98.94, 120.82, 128.94, 131.84, 144.44, 149.50, 152.41, 166.14.


Methyl 4-(4-methoxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (3):
white yellow-ish solid (0.71 g, 68 %) M.p. 197.5-198.3°C (lit. 190-191 °C).



1
H NMR
(400 MHz, DMSO-d6): δ 2.22 (s, 3H), 3.50 (s, 3H), 3.70 (s, 3H), 5.06 (s, 1H), 6.85 (d, 2H), 7.12 (d, 2H), 7.69 (s, 1H), 9.18 (s, 1H).

13
C NMR
(100 MHz, DMSO-d6): δ 18.26, 51.24, 55.49, 99.68, 114.21, 127.78, 137.28, 148.83, 152.61, 158.89, 166.31.


Lead Reference

F. Damkaci and A. Szymaniak, J. Chem. Ed. 2014, 91 (6), 943. DOI: 10.1021/ed400390k

Other References

G. Aridoss and Y.T. Jeong, Bulletin of the Korean Chem. Soc. 2010, 31 (4), 863. DOI:10.5012/bkcs.2010.31.04.863

Supplementary Information

e.g. Actual NMR spectra (as images or jdx files for interactive spectra), photographs of apparatus, TLC’s or crystals or videos. Please contact the ChemSpider team (ChemSpider-at-rsc.org) for help with this.
13C_NMR_PDT_1_Methyl 6-methyl- (CNMR_Full.pdf)
1H_NMR_PDT_1_Methyl 6-methyl-2 (HNMR_Full.pdf)
13C_NMR_PDT_2_Methyl 4-(4-brom (CNMR_Full.pdf)
1H_NMR_PDT_2_Methyl 4-(4-bromo (HNMR_Full.pdf)
13C_NMR_PDT_3_Methyl 4-(4-meth (CNMR_Full.pdf)
1H_NMR_PDT_3_Methyl 4-(4-metho (HNMR_Full.pdf)
Photo of products (1, 2, and 3 (BigPDTs06162017.jpg)

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Keywords: aldehydes, catalysis, heterocyclic compounds, ketones, lewis acid

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