Efficient Oxidative Conversion of Aldehydes to 2-Substituted Oxazolines and Oxazines Using (Diacetoxyiodo)benzene

Abstract

An efficient synthesis of 2-substituted oxazolines from aldehydes and 2-amino alcohol using (diacetoxyiodo)benzene as an oxidant, is reported. (Diacetoxyiodo)benzene acts as a mild dehydrogenating agent to convert the initially formed oxazolidine from aldehyde and 2-amino alcohol to furnish 2-substituted oxazoline. Similarly, 3-aminopropanol and aldehydes gives the corresponding 2-substituted oxazines.

hypervalent iodine - oxazolines - oxazines - oxidation - aldehydes

References and Notes

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Typical Experimental Procedure A mixture of an aldehyde (1.0 mmol) and an appropriate 2-amino alcohol (1.0 mmol) was stirred for 4 h at r.t. (Diacetoxyiodo)benzene (1.2 mmol) was then added to the above mixture and the resulting reaction mixture was again subjected for stirring for another 3-6 h. The progress of the reaction was monitored by TLC. After the completion of the reaction, H₂O (15 mL) was added and the mixture extracted with CH₂Cl₂ (2 × 15 mL). The combined organic extracts were dried over anhyd Na₂SO₄, concentrated in vacuo, and chromatographed to give 2-substituted oxazolines/oxazines.
Spectroscopic Data of Selected Products 2-(4-Nitrophenyl)-4,5-dihydrooxazole Mp 157-159 °C. IR (KBr): 3028, 2971, 2894, 1649, 1602, 1528, 1464, 1349, 1268, 1092, 952, 861, 710 cm^-1. ¹H NMR (CDCl₃): δ = 4.12 (t, J = 9.6 Hz, 2 H), 4.50 (t, J = 9.6 Hz, 2 H), 8.14 (d, J = 8.3 Hz, 2 H), 8.24 (d, J = 8.3 Hz, 2 H). LCMS [M + 1]: m/z = 193.
2-(4-Chlorophenyl)-4,5-dihydrooxazole Mp 116-118 °C (lit.^8d mp 118-119 °C). IR (KBr): 3062, 2964, 2891, 1724, 1638, 1590, 1474, 1280, 1073, 933, 824, 763 cm^-1. ¹H NMR (CDCl₃): δ = 3.72 (t, J = 9.4 Hz, 2 H), 3.97 (t, J = 9.4 Hz, 2 H), 7.40 (d, J = 7.9 Hz, 2 H), 7.68 (d, J = 7.9 Hz, 2 H). LCMS [M + 1]: m/z = 182.
2-(4-Methoxyphenyl)-4,5-dihydrooxazole Mp 138-139 °C. IR (KBr): 2958, 2849, 1711, 1620, 1505, 1255, 1158, 1024, 842, 775 cm^-1. ¹H NMR (CDCl₃): δ = 3.71 (s, 3 H), 3.76 (t, J = 9.2 Hz, 2 H), 3.91 (t, J = 9.2 Hz, 2 H), 7.49 (d, J = 7.6 Hz, 2 H), 6.87 (d, J = 7.6 Hz, 2 H). LCMS [M + 1]: m/z = 178.
2-(3,4,5-Trimethoxyphenyl)-4,5-dihydrooxazole Mp 83-85 °C. IR (KBr): 2940, 2849, 1711, 1638, 1584, 1407, 1225, 1128, 988, 769 cm^-1. ¹H NMR (CDCl₃): δ = 3.89 (m, 9 H), 4.07 (t, J = 9.3 Hz, 2 H), 4.43 (t, J = 9.3 Hz, 2 H), 6.97 (s, 1 H), 7.13 (s, 1 H). LCMS [M + 1]: m/z = 238.
2-(4-Tolyl)-4,5-dihydrooxazole Mp 143-144 °C (lit.^8d mp 144-145 °C). IR (KBr): 2928, 2879, 2855, 1650, 1596, 1389, 1286, 1055, 969, 811 cm^-1. ¹H NMR (CDCl₃): δ = 2.46 (s, 3 H), 3.75 (t, J = 9.3 Hz, 2 H), 3.91 (t, J = 9.3 Hz, 2 H), 7.63 (d, J = 7.4 Hz, 2 H), 7.22 (d, J = 7.6 Hz, 2 H). LCMS [M + 1]: m/z = 162.
4-Ethyl-4,5-dihydro-2-(4-methoxyphenyl)oxazole
Liquid. IR (KBr): 3068, 2964, 2873, 2855, 1645, 1489, 1268, 1085, 818 cm^-1. ¹H NMR (CDCl₃): δ = 0.92 (t, J = 9.1 Hz, 3 H), 1.36 (m, 2 H), 3.86 (s, 3 H), 3.97 (d, J = 9.2 Hz, 2 H), 4.14 (m, 1 H), 6.91 (d, J = 7.5 Hz, 2 H), 7.49 (d, J = 7.6 Hz, 2 H). LCMS [M + 1]: m/z = 206.
2-(4-Methoxyphenyl)-5,6-dihydro-4 H -[1,3]-oxazine Liquid. IR (KBr): 3012, 2958, 1637, 1602, 1510, 1358, 1307, 1283, 1273, 1256 cm^-1. ¹H NMR (CDCl₃): δ = 1.96 (quin, J = 5.8 Hz, 2 H), 3.58 (t, J = 5.4 Hz, 2 H), 3.81 (s, 3 H), 4.37 (t, J = 5.4 Hz, 2 H), 6.89 (d, J = 9.4 Hz, 2 H), 7.87 (d, J = 9.4 Hz, 2 H). LCMS [M + 1]: m/z = 192.
2-(4-Nitrophenyl)-5,6-dihydro-4 H -[1,3]-oxazine
Mp 143-144 °C (lit.²² mp 145-146 °C). ¹H NMR (CDCl₃): δ = 1.99 (quin, J = 5.8 Hz, 2 H), 3.66 (t, J = 5.6 Hz, 2 H), 4.37 (t, J = 5.6 Hz, 2 H), 8.07 (d, J = 9.2 Hz, 2 H), 8.22 (d, J = 9.3 Hz, 2 H). LCMS [M + 1]: m/z = 207.

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When the reaction mixture of cinnamaldehyde and 2-amino-2-methyl-1-propanol was stirred in the absence of DIB, the immediate precipitation of 2-styryloxazolidine was observed. This product was recrystallized from PE and subjected to LCMS analysis which showed a molecular ion peak [M + 1] at 204 corresponding to the formation of 4,4-dimethyl-2-styryloxazolidine. The reaction of 4,4-dimethyl-2-styryloxazolidine (1 mmol) with DIB (1.2 mmol) in CHCl₃ (10 mL) was independently carried out at r.t. stirring for another 3 h. After usual reaction workup, the formation of 4,5-dihydro-4,4-dimethyl-2-styryloxazole was realized in 38% yield.

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