Supporting Information
One-pot synthesis of novel oxazaphosphinanes under ultrasound
irradiation and solvent-free conditions
Billel Belhani ●Abdeslam Bouzina ● Malika Berredjem*● Nour-eddineAouf
Laboratory of Applied Organic Chemistry, Synthesis of biomolecules and molecular modelling Group,
Sciences Faculty, Chemistry Department, Badji Mokhtar - Annaba University, Box 12, 23000 Annaba,
Algeria
Email: mberredjem@yahoo.fr, malika.berredjem@univ-annaba.org
1. Apparatus………………………………...........................................................……………………....3
2. General procedure……………………………………………………………………………………..3
Scheme 1:One-potsynthesis of α-oxazaphosphinane under ultrasound irradiations…………….............3
Scheme 2: Mechanistic proposal for synthesis of oxazaphosphinane.…….……………………….....…4
3. Selected Spectra data……………………………………….……………………………………..…..4
1
H NMR spectrum: (2R,3R,5S)-2-ethoxy-5-isobutyl-3-phenyl-[1,4,2]-oxazaphosphinane 2-oxide ….....7
13
C NMR spectrum: (2R,3R,5S)-2-ethoxy-5-isobutyl-3-phenyl-[1,4,2]-oxazaphosphinane 2-oxide..…..7
31
P NMR spectrum: (2R,3R,5S)-2-ethoxy-5-isobutyl-3-phenyl-[1,4,2]-oxazaphosphinane 2-oxide…....8
1
H NMR spectrum: (2R,3R,5R)-2-ethoxy-5-isopropyl-3-phenyl-[1,4,2]-oxazaphosphinane 2-oxide…..8
1
H NMR spectrum: (2R,3R,5S)-5-benzyl-2-ethoxy-3-phenyl-[1,4,2]-oxazaphosphinane 2-oxide…….…9
13
C NMR spectrum: (2R,3R,5S)-5-benzyl-2-ethoxy-3-phenyl-[1,4,2]-oxazaphosphinane 2-oxide...........9
31
P NMR spectrum: (2R,3R,5S)-5-benzyl-2-ethoxy-3-phenyl-[1,4,2]-oxazaphosphinane 2-oxide….....10
Mass spectrum: (2R,3R,5S)-5-benzyl-2-ethoxy-3-phenyl-[1,4,2]-oxazaphosphinane 2-oxide….....….10
1
H NMR spectrum:(2R,3R,5S)-5-((1H-indol-3-yl)methyl)-2-ethoxy-3-phenyl [1,4,2]oxazaphosphinane
2-oxide......................................................................................................................................................11
1. Apparatus
Sonication was performed in a FUNGILAB ultrasonic bath with a frequency of 40 KHz and an output
power of 250 W. The reactions were carried out in an open glass tube (diameter: 25 mm; thickness: 1
mm; volume: 20 mL) at room temperature. Melting points were uncorrected and measured in open
capillary tubes on an Electro thermal apparatus. 1H-NMR,
13
C-NMR and
31
P-RMN spectra were
recorded on a Bruker spectrometer 250 or 400 MHz instrument using TMS as internal standard and
CDCl3 as solvent. Mass spectra were recorded on a shimadzu QP 1100 Ex mass spectrometer operating
at an ionization potential of 70 Ev. IR spectra were recorded as KBr pellets on a Perkin Elmer 781
spectrophotometer and an Impact 400 Nicolet FT-IR spectrophotometer.
2. General procedure
In a 10 ml round bottom flask taken a mixture of aldehyde 1 mmol and aminoalcohol 1 mmol at room
temperature and then triethylphosphite 1 mmol was added. Then reaction mixture was subjected to the
ultrasonication for appropriate time. After completion of the reaction, as indicated by TLC, silica gel;
dichloromethane:methanol (9:1), a (4:1) mixture of diethyl ether and n-hexane was added and the
mixture was cooled to 6° C overnight. The product was finally filtered and dried.
Scheme 1: One-potsynthesis of α-oxazaphosphinane under ultrasound irradiations.
Scheme 2: Mechanistic proposal for synthesis of oxazaphosphinane.
3. Selected Spectral data:
(2R,3R)-2-ethoxy-3-phenyl-[1,4,2]-oxazaphosphinane 2-oxide(4a, C11H16NO3P)
White powder; 93 % yield; M.p.: 115-117 °C.
P NMR (160 MHz, CDCl3): δ= 15.8 ppm; 1H NMR
31
(250 MHz, CDCl3): δ= 1.2 (dt, JHH = 7.1 Hz, JPH= 2.9 Hz, 3H, CH3-CH2), 2.2 (s, 1H, NH), 3.3 (m, 2H,
CH2-CH2), 3.8-3.9 (m, 2H, CH2-CH2-O), 4.3-4.5 (dq, JHH = 7.2 Hz, JPH = 1.5 Hz,2H,CH3-CH2-O-P),
4,9 (dd, JHH= 9.9 Hz, 1H, Ar-*CH-NH), 7.10-7.50 (m, 5H, HAr) ppm; 13C NMR (100 MHz, CDCl3): δ
= 16.5 (CH3), 54 (CH2), 63.9 (CH2), 66.9 (*CH), 68.3 (CH2), 121.5(CH), 125 (2CH), 129.1 (2CH),
135.7 (C) ppm; IR (KBr):ѵ= 3145, 3110, 1455, 1245, 1040, 1031 cm-1; MS: (m/z) = 242 (M+1); Anal.
Calc. for C11H16NO3P:C, 54.77; H, 6.69; N, 5.81; Found: C, 54.74; H, 7.01; N, 5.72.
(2R,3R,5S)-5-methyl-2-ethoxy-3-phenyl-[1,4,2]-oxazaphosphinane 2-oxide(4b, C12H18NO3P)
White powder; 89 % yield; M.p.: 118-120 °C.
P NMR (160 MHz, CDCl3): δ= 16.9 ppm; 1H NMR
31
(250 MHz, CDCl3): δ= 1.1 (d, JHH = 7.5 Hz, 3H, CH3-CH), 1.2 (dt, JHH = 7.5 Hz, JPH = 3.4 Hz, 3H,
CH3-CH2), 1.9 (s, 1H, NH), 3.1 (m, 1H, *CH-CH2), 3.7-3.8 (m, 2H, *CH-CH2-O), 4.1-4.3 (dq, JHH =
7.7 Hz, JPH = 1.9 Hz,2H, CH3-CH2-O-P), 4.5 (dd, JHH= 11.5 Hz, 1H, Ar-*CH-NH), 7.1-7.6 (m, 5H,
HAr) ppm; 13C NMR (100 MHz, CDCl3): δ = 16.8 (CH3), 38 (CH3), 57 (*CH), 61.2 (CH2), 64.3 (*CH),
67.8 (CH2), 123.8(CH), 127.4 (2CH), 130 (2CH), 139.7 (C) ppm; IR (KBr):ѵ= 3151, 3130, 1474, 1257,
1035, 1016 cm-1; MS: (m/z) = 256 (M+1); Anal. Calc. for C12H18NO3P:C, 56.47; H, 7.11; N, 5.49;
Found: C, 56.58; H, 7.41; N, 5.43.
(2R,3R,5R)-2-ethoxy-5-isopropyl-3-phenyl-[1,4,2]-oxazaphosphinane 2-oxide(4c, C14H22NO3P)
White powder; 90 % yield; M.p.: 122-124 °C.
P NMR (160 MHz, CDCl3): δ= 17.5 ppm; 1H NMR
31
(250 MHz, CDCl3): δ= 1.1 (d, JHH= 7.6 Hz, 6H, 2CH3), 1.2 (t, JHH = 7.1 Hz, JPH = 2.7 Hz, 3H, CH3CH2), 1.8 (m, 1H, CH-iPr), 2.1 (s, 1H, NH), 3.0 (m, 1H, *CH-CH2), 3.8-3.9 (m, 2H, *CH-CH2-O), 4.14.5 (dq, JHH = 10.3 Hz, JPH = 3.1 Hz,2H, CH3-CH2-O-P), 4,6 (dd, JHH= 9.7 Hz, 1H, Ar-*CH-NH), 7.27.7 (m, 5H, HAr) ppm; 13C NMR (100 MHz, CDCl3): δ = 16.3 (CH3), 21 (CH3), 21.2 (CH3), 36 (CH),
52 (*CH), 59 (CH2), 66.4 (*CH), 69.2 (CH2), 127.2 (CH), 128.5 (2CH), 129.4 (2CH), 138.4 (C) ppm;
IR (KBr):ѵ = 3180, 3120, 1490, 1239, 1025, 1022 cm-1; MS: (m/z) = 284 (M+1); Anal. Calc. for
C14H22NO3P:C, 59.35; H, 7.83; N, 4.94; Found: C, 58.98; H, 7.58; N, 4.87.
(2R,3R,5S)-2-ethoxy-5-isobutyl-3-phenyl-[1,4,2]-oxazaphosphinane 2-oxide (4d, C15H24NO3P)
White powder; 81 % yield; M.p.: 119-121°C.
P NMR (160 MHz, CDCl3): δ= 16.8 ppm; 1H NMR
31
(400 MHz, CDCl3): δ= 0.9 (d, JHH= 6.6 Hz, 6H, 2CH3), 1.2 (dt, JHH = 7.4 Hz, JPH= 2.4 Hz, 3H, CH3CH2-O-P),1.4-1.6 (m, 2H, *CH-CH2-iPr), 1.8 (m, 1H, CH3-CH-CH3), 1.9 (s, 1H, NH), 3.2 (m, 1H,
*CH-CH2), 3.8-3.9 (m, 2H, *CH-CH2-O), 4.1-4.4 (dq, JHH = 7.2 Hz, JPH = 1.6 Hz,2H, CH3-CH2-O-P),
4.9 (dd, JHH = 12.7 Hz, 1H, Ar-*CH-NH), 7.2-7.60 (m, 5H, HAr) ppm; 13C NMR (100 MHz, CDCl3):
δ= 16.4 (CH3), 23.1 (CH3), 24.8 (CH3), 34 (CH), 39.5 (CH2), 55 (*CH), 62.5 (CH2), 66.4 (*CH), 72.2
(CH2), 127.2 (CH), 128.5 (2CH), 129.2 (2CH), 139.4 (C) ppm; IR (KBr):ѵ = 3220, 3140, 1460, 1252,
1025, 1010 cm-1; MS: (m/z) = 298 (M+1); Anal. Calc. for C15H24NO3P: C, 60.59; H, 8.14; N, 4.71;
Found: C, 60.32; H, 8.02; N, 4.33.
(2R,3R,5S)-5-benzyl-2-ethoxy-3-phenyl-[1,4,2]-oxazaphosphinane 2-oxide(4e, C18H22NO3P)
White powder; 87 % yield; M.p.: 103-105 °C. 31P NMR (160 MHz, CDCl3): δ = 14.01 ppm; 1H NMR
(250 MHz, CDCl3): δ = 1.10 (dt, JHH = 10.5 Hz, JPH = 5.1 Hz, 3H, CH3-CH2), 1.8 (s, 1H, NH), 2.7 (m,
1H, *CH-CH2), 3.1-3.5 (m, 2H, Ar-CH2-*CH), 3.7-4.0 (m, *CH-CH2-O), 4.1-4.4 (dq, JHH = 10.8 Hz,
JPH = 3.9 Hz, 2H, CH3-CH2-O-P), 4,7 (dd, JHH= 8.4 Hz, 1H, Ar-*CH-N), 7.2-7.6 (m, 10H, HAr) ppm;
13
C NMR (100 MHz, CDCl3): δ = 16.4 (CH3), 37.4 (CH2), 55.27 (*CH), 55.63 (CH2), 59.71 (*CH),
61.12 (CH2), 127.4 (CH), 127.12 (CH), 127.26 (CH), 127.64 (CH), 128.04 (CH), 128.09 (CH), 128.19
(CH), 128.61 (CH), 128.8 (CH), 129.1 (CH), 129.2 (C), 136.9 (C) ppm; IR (KBr):ѵ = 3220, 3160,
1450, 1246, 1051, 1022 cm-1; MS: (m/z) = 332 (M+1); Anal. Calc. for C18H22NO3P:C, 65.25; H, 6.69;
N, 4.23; Found: C, 65.05; H, 6.49; N, 4.52.
(2R,3R,5S)-5-((1H-indol-3-yl)methyl)-2-ethoxy-3-phenyl-[1,4,2]-oxazaphosphinane
2-oxide
(4f,
C20H23N2O3P)
White cristal; 79% yield; M.p.: 123-125°C. 31P NMR (160 MHz, CDCl3): δ = 17.5 ppm; 1H NMR (250
MHz, CDCl3): δ =1.1 (dt, JHH = 7 Hz, JPH = 1.84 Hz, 3H, CH3-CH2), 1.8 (s, 1H, NH), 2.2 (dd, JHH =
10.1, 2H, CH2-C=C), 2.9 (m, 1H,*CH-CH2), 3.6-4.0 (m, 2H, *CH -CH2-O), 4.1-4.5 (dq, JHH = 7.2 Hz,
JPH = 2 Hz, 2H, CH3-CH2-O-P), 4.8 (dd, JHH = 7.1 Hz, 1H, Ar-*CH-NH), 7.18 (s, 1H, CH), 7.2-7.7 (m,
9H, HAr), 8.2 (s, 1H, NH) ppm ; 13C NMR (100 MHz, CDCl3):δ = 16.4 (CH3), 32.1 (CH2), 61.5 (*CH),
63.4 (CH2), 66 (*CH), 72.2 (CH2), 114.5 (CH), 118.9 (CH), 119.5 (2CH), 121 (2CH), 123.4 (2CH),
127 (2CH), 127.6 (C), 128.5 (C), 129.4 (C), 132 (C), 138.3 (C) ppm; IR (KBr):ѵ = 3280, 3120, 1510,
1460, 1241, 1025, 1020 cm-1; MS: (m/z) = 371 (M+1); Anal. Calc. for C20H23N2O3P: C, 64.86 ; H, 6.26
; N, 7.56; Found: C, 64.51; H, 6.29; N, 7.17.
1
H NMR spectrum:(2R,3R,5S)-2-ethoxy-5-isobutyl-3-phenyl-[1,4,2]-oxazaphosphinane 2-oxide
13
C NMR spectrum:(2R,3R,5S)-2-ethoxy-5-isobutyl-3-phenyl-[1,4,2]-oxazaphosphinane 2-oxide
31
P NMR spectrum:(2R,3R,5S)-2-ethoxy-5-isobutyl-3-phenyl-[1,4,2]-oxazaphosphinane 2-oxide
1
H NMR spectrum: (2R,3R,5R)-2-ethoxy-5-isopropyl-3-phenyl-[1,4,2]-oxazaphosphinane 2-oxide
1
H NMR spectrum: (2R,3R,5S)-5-benzyl-2-ethoxy-3-phenyl-[1,4,2]-oxazaphosphinane 2-oxide
13
C NMR spectrum: (2R,3R,5S)-5-benzyl-2-ethoxy-3-phenyl-[1,4,2]-oxazaphosphinane 2-oxide
31
P NMR spectrum: (2R,3R,5S)-5-benzyl-2-ethoxy-3-phenyl-[1,4,2]-oxazaphosphinane 2-oxide
Mass spectrum: (2R,3R,5S)-5-benzyl-2-ethoxy-3-phenyl-[1,4,2]-oxazaphosphinane 2-oxide
1
H NMR spectrum: (2S,3S,5R)-5-((1H-indol-3-yl)methyl)-2-ethoxy-3-phenyl-[1,4,2]oxazaphosphinane 2-oxide