2096
V. I. Boyko et al.
SHORT PAPER
All the reactions were carried out in freshly distilled, anhydrous sol-
vents under moisture-free conditions. Melting points were deter-
mined on a Boetius apparatus and are uncorrected. 1H NMR spectra
were recorded in CDCl3 at 298 K on a Varian VXR-300 instrument
at 300 MHz and all shifts are referenced to TMS.
4-Hydroxyacetylmorpholine (2f)
Crystallized from EtOAc–hexane, 1:20.
Yield: 93.2%; mp 72–74 °C (Lit.11 70–72 °C).
1H NMR (CDCl3): d = 4.15 (s, 2 H, CH2O), 3.67 (m, 6 H, NCH2 and
2 × OCH2), 3.27 (m, 2 H, NCH2).
2,2-Dimethyl-1,3-dioxolan-4-one (1)
N-Ethyl-N-Phenyl-2-hydroxyacetamide (2g)
A suspension of phosphorus pentoxide (40 g, 0.28 mol) in Et2O
(100 mL) was cooled to –18 °C and an ice-cold solution of glycolic
acid (10 g, 0.13 mol) in acetone (50 mL) was added dropwise with
efficient stirring. When the phosphorus pentoxide formed a lump, it
was kneaded with a spatula. The resulting solution was filtered and
the solvents were removed in vacuo to give an oil that was distilled
under reduced pressure to give 1.
A solution of N-ethylaniline (46.57 g, 260 mmol), dioxolane (6.03
g, 52 mmol) and two drops of H2SO4, in toluene (90 mL) was re-
fluxed for 24 h. After cooling, the solvent was removed under re-
duced pressure and the resulting amide was distilled in vacuo two
times.
Yield: 2.75 g (29.5%); bp 126–128 °C/1 mmHg; mp 37–39 °C
(Lit.12 39–41 °C).
1H NMR (CDCl3): d = 7.42 (m, 3 H, Ph), 7.16 (m, 2 H, Ph), 4.47 (br
s, 1 H, OH), 3.79 (m, 2 H, NCH2), 3.76 (s, 2 H, OCH2), 1.14 (t,
J = 7.2 Hz, 3 H, CH3).
Yield: 9.96 g (65.2%); colorless liquid; bp 49–50 °C/15 mmHg
(Lit.15 41 °C/11 mmHg).
1H NMR (CDCl3): d = 4.34 (s, 2 H, CH2), 1.59 (s, 6 H, CH3).
Syntheses of Amides 2a–g; General Procedure
A solution of amine (70 mmol) and dioxolane (35 mmol) in toluene
(60 mL) was refluxed for 14 h. After cooling, solvent and excess of
amine was removed under reduced pressure and the resulting
amides were distilled in vacuo for compounds 2a–e and 2g, or re-
crystallized (2f).
Acknowledgment
The authors express their thanks to A. V. Yakovenko for helpful and
valuable discussions.
N,N-Diethyl-2-hydroxyacetamide (2a)
Yield: 72%; bp 64–65 °C/0.08 mmHg (Lit.7a 119–124 °C/17
mmHg).
1H NMR (CDCl3): d = 4.15 (s, 2 H, CH2O), 3.43 (br s and q, 3 H,
OH and NCH2), 3.14 (q, 2 H, NCH2), 1.16 (m, 6 H, 2 × CH3).
References
(1) (a) Kim, B. P.; Park, N. K.; Hong, K. S.; Park, J. E.; Kwon,
Y. W. WO 9947491, 1999; Chem. Abstr. 1999, 131,
228550p. (b) Kai, H.; Horita, Y.; Miri, N.; Ide, K.; Takase,
A. Nippon Noyaku Gakkaishi 1998, 23, 255; Chem. Abstr.
1998, 129, 340796h. (c) Baltruchat, H. S.; Newton, T. W.;
Kleemann, A.; Mengel, W. WO 9925702, 1999; Chem.
Abstr. 1999, 130, 352273u.
(2) Maruta, T.; Kondo, K.; Furukava, K.; Oka, M. WO 9809960,
1998; Chem. Abstr. 1998, 128, 230383t.
(3) Oza, H.; Joshi, D.; Parekh, H. Indian J. Chem., Sect. B: Org.
Chem. Incl. Med. Chem. 1998, 37, 822; Chem. Abstr. 1999,
130, 110191y.
(4) Ban, M.; Taguchi, H.; Katsushima, T.; Takahashi, M.;
Shinoda, K.; Watanabe, A.; Tominaga, T. Bioorg. Med.
Chem. 1998, 6, 1069.
(5) Ota, T.; Nakanishi, M.; Aibe, I.; Taguchi, M.; Tomisawa, K.
JP 11092454, 1999; Chem. Abstr. 1999, 130, 306598f.
(6) Tarpanov, V.; Vlanov, R.; Penkov, M.; Krikorian, D.;
Parushev, S.; Mechkarova, P.; Angelova, N.; Pehunack, W.
Synth. Commun. 1999, 29, 15.
N,N-Di(n-propyl)-2-hydroxyacetamide (2b)
Yield: 56%; bp 123–124 °C/12 mmHg.
1H NMR (CDCl3): d = 4.14 (s, 2 H, CH2O), 3.67 (br s, 1 H, OH),
3.33 (m, 2 H, NCH2), 3.02 (m, 2 H, NCH2), 1.56 (m, 4 H, 2 ×
CH2CH3), 0.895 (m, 6 H, 2 × CH3).
Anal. Calcd for C8H17NO2: C, 60.35; H, 10.76; N, 8.80. Found: C,
60.40; H, 10.94; N, 8.64.
N,N-Di(n-butyl)-2-hydroxyacetamide (2c)
Yield: 72.8%; bp 82–83 °C/0.02 mmHg.
1H NMR (CDCl3): d = 4.14 (s, 2 H, CH2O), 3.71 (br s, 1 H, OH),
3.36 (t, J = 7.6 Hz, 2 H, NCH2), 3.05 (t, J = 7.6 Hz, 2 H, NCH2),
1.52 (m, 4 H, 2× NCH2CH2), 1.32 (m, 4 H, 2 × CH2CH3), 0.94 (t,
J = 7.2 Hz, 3 H, CH3), 0.92 (t, J = 7.2 Hz, 3 H, CH3).
(7) (a) Andreas, F.; Sowada, R.; Scholz, J. J. Prakt. Chem. 1962,
18, 141. (b) Kato, S.; Mizutani, Y.; Izumi, A. JP 54032418,
1971; Chem. Abstr. 1979, 91, 56388d. (c) Diehr, H. J. DE
3222229, 1984; Chem. Abstr. 1984, 100, 138613s.
(d) Diehr, H. J.; Krall, H. D.; Mhrmann, K. H. DE 3244956,
1984; Chem. Abstr. 1984, 101: 90779s. (e) Ricci, A.;
Romanelli, M. N.; Taddei, M. Synthesis 1983, 319.
(8) Khalaj, A.; Nahid, E. Synthesis 1985, 1153.
(9) Willstätter, R.; Königsberger, F. Ber. Dtsch. Chem. Ges.
1923, 2107.
(10) Boyko, V. I.; Severenchuk, I. M.; Rodik, R. V.; Yakovenko,
A. V.; Kalchenko, V. I. Ukrainian Patent 200700431, 2007.
(11) Fischer, A.; Rohr, W. DE 2219923, 1974; Chem. Abstr.
1974, 80: 27127k.
Anal. Calcd for C10H21NO2: C, 64.13; H, 11.30; N, 7.48. Found: C,
64.38; H, 11.40; N, 7.42.
N,N-Di(n-hexyl)-2-hydroxyacetamide (2d)
Yield: 82.3%; bp 125–128 °C/0.02 mmHg.
1H NMR (CDCl3): d = 4.13 (s, 2 H, CH2O), 3.35 (br s, 1 H, OH),
3.35 (m, 2 H, NCH2), 3.04 (m, 2 H, NCH2), 1.53 (m, 4 H, 2 ×
NCH2CH2), 1.28 [m, 12 H, 2 × -(CH2)3-], 0.88 (m, 6 H, 2 × CH3).
Anal. Calcd for C14H29NO2: C, 69.07; H, 12.03; N, 5.75. Found: C,
69.09; H, 12.30; N, 6.02.
4-Hydroxyacetylpiperidine (2e)
Yield: 75%; bp 135–138 °C/1 mmHg (Lit.7e 76–80 °C/0.08
mmHg).
(12) Fischer, A.; Hamprecht, G.; Mangold, D.; Rohr, W. US
3870740, 1975; Chem. Abstr. 1976, 85, 77682m.
1H NMR (CDCl3): d = 4.14 (s, 2 H, CH2O), 3.60 (m, 2 H, NCH2),
3.43 (br s, 1 H, OH), 3.20 (m, 2 H, NCH2), 1.66 (m, 2 H, CH2), 1.28
(m, 4 H, 2 × CH2).
Synthesis 2007, No. 14, 2095–2096 © Thieme Stuttgart · New York