Clay catalyzed conversion of isatoic anhydride to 2-(o-aminophenyl)oxazolines

Article abstract of DOI:10.1039/a908564e

A simple and environmentally safe procedure for the preparation of 2-(o-aminophenyl)oxazolines from isatoic anhydride is presented. A series of chiral derivatives of the title compound is prepared in moderate yield via natural kaolinitic clay catalyzed re

Full text of DOI:10.1039/a908564e

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Clay catalyzed conversion of isatoic anhydride† to 2-(o-amino-
phenyl)oxazolines
Anil S. Gajare, Nadim S. Shaikh, Gowda K. Jnaneshwara, Vishnu H. Deshpande,*
Thottappilli Ravindranathan and Ashutosh V. Bedekar*
1
Division of Organic Chemistry: Technology, National Chemical Laboratory, Pune - 411 008,
India. Fax: ϩ91 020 5893614
Received (in Cambridge, UK) 27th October 1999, Accepted 2nd February 2000
A simple and environmentally safe procedure for the preparation of 2-(o-aminophenyl)oxazolines from isatoic
anhydride is presented. A series of chiral derivatives of the title compound is prepared in moderate yield via natural
kaolinitic clay catalyzed reactions with optically pure 2-aminoalcohols. Reaction of polymer-supported isatoic
anhydride under these conditions with chiral 2-aminoalcohols proceeds to furnish polymer-anchored analogues.
A series of derivatives of 2-(o-aminophenyl)oxazolines were
Introduction
synthesized with different 2-aminoalcohols and the results are
summarized in Table 1. Commercially available Montmorillon-
ite K10 was also found to be an efficient catalyst and the reac-
tion was found to proceed much more quickly when carried out
under microwave conditions (entry 1). However, experiments
with ZnCl2 gave a slightly lower yield (entry 1) for this reaction.
As we were interested in chiral derivatives of this type of com-
pound, different optically pure 2-aminoalcohols were used for
this reaction to furnish the desired products in low to moderate
yields. Slightly modified reactions with an excess of 1 showed
some improvement in the conversion as is evident from entries
4 to 7. The amino oxazoline from entry 6 was converted to its
NHTs derivative, the optical rotation of which was in accord
with the reported value,4a indicating no loss of optical purity
during the reaction.
Oxazoline is an important functionality as a protecting group1
in organic synthesis. The optically active aromatic oxazolines
are used extensively to control the stereochemistry in many
asymmetric transformations.2 In our previous communi-
cations3 we have demonstrated the use of natural kaolinitic clay
as an efficient catalyst for the preparation of 2-oxazolines from
nitriles. We wish to present the application of this catalyst to
the conversion of isatoic anhydride, 1, to 2-(o-aminophenyl)-
oxazolines. Chiral analogues of these compounds have been
used in asymmetric synthesis.4 The chemistry of 1 has been
reviewed at length by Coppola;5 the example of the preparation
of 2,3-dihydrobenzothiazol from 1 and 2-aminothiophenol6
is mentioned therein. Coppola has also recently reported the
preparation of polymer-supported isatoic anhydride and its use
as a scavenger of amines.7 We have an interest in the prepar-
ation of polymer-supported, chiral oxazoline based ligands for
application in heterogeneous asymmetric catalytic reactions.
We wish to report our results on the reactions of polymer-
supported isatoic anhydride under these conditions to furnish
the polymer-anchored title compound.
The catalytic conversion of 1 also works with 2-aminophenol
and 2-aminothiophenol (Scheme 2) with the formation of 9 and
Results and discussions
Reaction of 1 with 2-aminoalcohol was carried out in dry
chlorobenzene at 120 ЊC in the presence of acidic kaolinitic
clay8 as the catalyst to furnish 2-(o-aminophenyl)oxazoline
(Scheme 1). We presume that the Lewis acidic sites of the
Scheme 2
10, respectively; only a little amount of disulfide was formed in
latter case.
Our continuing aim is the preparation of polymer-supported
oxazolinyl ligands for heterogeneous asymmetric catalysis. We
prepared the polymer-supported isatoic anhydride 11 from
chloromethylated styrene–divinylbenzene polymer (4.8 equiv.
ClϪ gϪ1) by the procedure described by Coppola.7 A sample of
11 was exposed to 2.5 equivalents of -2-aminobutanol and a
catalytic amount of kaolinitic clay in chlorobenzene to afford
polymer-anchored amino oxazoline 12 (Scheme 3).
The FT-IR analysis of the polymer beads of 12 showed a
peak at 3419 cmϪ1 and the absence of the two carbonyl peaks
at 1778 and 1725 cmϪ1 of the polymer 11 indicated successful
conversion. Two more chiral polymer-supported amino oxazo-
lines 13 and 14 were prepared by the same method using
-isoleucinol and -phenylalaninol as the aminoalcohols.
Scheme 1
catalyst assist the nucleophilic attack of the amino group on
C-4 of 1, which is followed by cyclization to give the oxazoline.
The final product is formed by the loss of carbon dioxide to give
the free amine.
† The IUPAC name for isatoic anhydride is (2H)-3,1-benzoxazine-2,4-
(1H)-dione.
DOI: 10.1039/a908564e
J. Chem. Soc., Perkin Trans. 1, 2000, 999–1001
This journal is © The Royal Society of Chemistry 2000
999

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Table 1 Catalytic conversion of isatoic anhydride to 2-(o-amino-
phenyl)oxazolinesa
Yield
Entry
1
Aminoalcohol
Product
(%)b
65
70c
45d
55e
40
2
3
45c
41f
4
5
6
7
50
55f
Scheme 3
Montmorillonite K10 and isatoic anhydride were purchased
from Aldrich Chemicals. Merrifield resin, the copolymer of
chloromethylpolystyrene cross-linked with 1% divinylbenzene,
58f
with loading of 4.8 equiv. ClϪ Ϫ1 resin was obtained from Ion
g
Exchange (India) Ltd. as a gift sample. Optically pure amino
alcohols were prepared from chiral amino acids by the known
procedure.9 Chlorobenzene was distilled over CaH2 and stored
over activated molecular sieves.
35
62f
2-(4,4-Dimethyl-4,5-dihydro-1,3-oxazol-2-yl)aniline 2
A mixture of 1 (0.50 g; 3.06 mmol), 2-amino-2-methylpropan-
1-ol (0.68 g; 7.64 mmol) and kaolinitic clay (0.10 g) was stirred
in chlorobenzene (5 mL) at ca. 120 ЊC for 20 h. After comple-
tion of the reaction, the catalyst was filtered off and the product
purified by column chromatography on neutral alumina to
afford compound 2 as a white solid (0.38 g; 65%). Mp 103.6–
106.0 ЊC; IR ν 3439, 3187, 3151, 1401, 1329, 1185, 752 cmϪ1; 1H
NMR δ 1.35 (s, 6H), 4.05 (s, 2H), 6.35 (br s, 2H), 6.65 (m, 1H),
7.15–7.25 (m, 2H), 7.65–7.70 (m, 1H); MS m/z (%) 190 (Mϩ,
91), 175 (100), 145 (51), 130 (65), 118 (76), 92 (20), 65 (13).
Calcd. for C11H14N2O: C, 69.47; H, 7.37; N, 14.74. Found: C,
69.58; H, 7.31; N, 14.89%.
70f
a Isatoic anhydride was heated in dry chlorobenzene under Ar with
2-aminoalcohol (2.5 eq.), catalyst (20% w/w) for 20 h. b Isolated yield.
All the compounds were characterized by usual spectral methods.
c With microwave irradiation in a domestic oven for 20 min. d With
ZnCl2 (5 mol%). e With Montmorillonite K10 (20% w/w). f With 2 eq.
of isatoic anhydride.
The same procedure was followed for the preparation of all
the 2-(o-aminophenyl)oxazolines using the appropriate amino-
alcohol as listed in Table 1.
Thus in this paper we have presented a simple and efficient
procedure for preparation of 2-(o-aminophenyl)oxazolines
from isatoic anhydride. We have also presented our initial
results on the preparation of the polymer-supported title
compounds.
2-(4,5-Dihydro-1,3-oxazol-2-yl)aniline 3
Light yellow oil. IR ν 3379, 3187, 3120, 1625, 1390, 1260, 747
1
cmϪ1; H NMR δ 4.00–4.12 (m, 2H), 4.12–4.25 (m, 2H), 6.05
(br s, 2H), 6.55–6.85 (m 2H), 7.15 (m, 1H), 7.70 (m, 1H); MS
m/z (%) 162 (Mϩ, 100), 130 (48), 118 (70), 106 (55), 92 (20), 65
(20). Calcd. for C9H10N2O: C, 66.66; H, 6.17; N, 17.28. Found:
C, 66.45; H, 6.28; N, 17.42%.
Experimental
Melting points were recorded on a Büchi melting point B-540
apparatus and are uncorrected. The 1H NMR spectra were
recorded in CDCl3 with TMS as an internal standard on a
Bruker AC 200 NMR spectrometer (200 MHz). Mass spectra
were recorded on a Finnigan MAT 1020B 70 eV GC-MS (EI)
instrument. The FT-IR spectra were recorded on a ATI-
Mattson Res. Series 1 spectrometer and Microanalyses were
carried out on a Carlo-Erba instrument. Optical rotations were
measured on a JASCO DIP-181 digital polarimeter at 24 ЊC
and are reported in units of 10Ϫ1 deg cm2 gϪ1. Kaolinitic clay
was received from RRL, Trivandrum as a gift sample,8b and
2-(4-Isopropyl-4,5-dihydro-1,3-oxazol-2-yl)aniline 4
Pale yellow oil. [α]D Ϫ1.35 (0.85, CHCl3); IR ν 3395, 3288, 2955,
1
1686, 1633, 1598, 1456, 1047, 746 cmϪ1; H NMR δ 0.90–1.10
(2 d, J = 7.8 Hz, 6H), 1.65–1.90 (m, 1H), 3.95–4.20 (m, 2H),
4.22–4.40 (m, 1H), 6.50 (br s, 2H), 6.55–6.80 (m 2H), 7.10–7.30
(m, 1H), 7.60–7.72 (m, 1H); MS m/z (%) 204 (Mϩ, 50), 193 (10),
161 (100), 133 (32), 119 (25), 106 (10), 92 (15). Calcd. for
1000
J. Chem. Soc., Perkin Trans. 1, 2000, 999–1001

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C12H16N2O: C, 70.59; H, 7.84; N, 13.72. Found: C, 70.91; H,
7.82; N, 13.64%.
Polymer-supported amino oxazoline 12 (Scheme 3)
A mixture of 11 (0.50 g; with about 1.6 mmol of isatoic
anhydride), -2-aminobutanol (0.36 g, 4.00 mmol) and kaoli-
nitic clay (0.10 g; 20% w/w) was agitated in dry chlorobenzene
(3 mL) at 100 ЊC for 24 h. The resin beads were isolated
and washed with organic solvents [water–THF (50:50, 25:75,
10:90 and 0:100) followed by acetone, methanol and di-
chloromethane] and dried under high vacuum. The polymer 12
was characterized by FT-IR analysis. IR ν 3419, 3212, 2918,
2-(4-sec-Butyl-4,5-dihydro-1,3-oxazol-2-yl)aniline 5
Pale yellow oil. [α]D ϩ7.94 (1.26, CHCl3); IR ν 3462, 3283,
2960, 1634, 1599, 1491, 1046, 969, 748 cmϪ1; 1H NMR δ 0.88 (d,
J = 6.0 Hz, 3H), 0.93 (t, J = 6.0 Hz, 3H), 1.15–1.40 (m, 1H),
1.50–1.80 (m, 2H), 4.00 (m, 1H), 4.15–4.40 (m, 2H), 6.15 (br s,
2H), 6.52–6.55 (m 2H), 7.10–7.30 (m, 1H), 7.65–7.75 (d, J = 8.0
Hz, 1H); MS m/z (%) 218 (Mϩ, 45), 187 (10), 161 (100), 133
(40), 118 (18), 106 (10), 92 (8). Calcd. for C13H18N2O: C, 71.56;
H, 8.27; N, 12.84. Found: C, 71.10; H, 8.71; N, 12.20%.
2852, 1621, 1570, 1425, 1322, 1213, 769 cmϪ1
.
Polymer-supported amino oxazoline 13 (Scheme 3)
Prepared by the same process as for 12 but with -isoleucinol as
the 2-aminoalcohol. IR ν 3388, 3282, 2918, 2853, 1616, 1500,
2-(4-Benzyl-4,5-dihydro-1,3-oxazol-2-yl)aniline 6
Light yellow thick oil. [α]D ϩ26.54 (1.04, CHCl3); IR ν 3448,
1456, 1369, 1218, 742 cmϪ1
.
3320, 3042, 2901, 1629, 1480, 1200, 1150, 769 cmϪ1; H NMR
1
δ 2.75 (dd, J = 14.0 and 8.0 Hz, 1H), 3.15 (dd, J = 14.0 and 6.0
Hz, 1H), 4.05 (m, 1H), 4.30 (m, 1H), 4.50–4.70 (m, 1H), 6.15
(br s, 2H), 6.60–6.75 (m, 3H), 7.15–7.45 (m, 5H), 7.65 (m, 1H);
MS m/z (%) 252 (Mϩ, 80), 224 (2), 160 (40), 131 (40), 118 (90),
91 (50), 83 (100), 71 (2). Calcd. for C16H16N2O: C, 76.19; H,
6.35; N, 11.11. Found: C, 76.22; H, 6.39; N, 11.52%.
Polymer-supported amino oxazoline 14 (Scheme 3)
Prepared by the same process as for 12 but with -phenyl-
alaninol as the 2-aminoalcohol. IR ν 3460, 3309, 2955, 2867,
1590, 1495, 1037, 753, 697 cmϪ1
.
Acknowledgements
2-(4-Phenyl-4,5-dihydro-1,3-oxazol-2-yl)aniline 7
We are grateful to Dr M. Lalithambika of RRL, Trivandrum
for the sample of kaolinitic clay. We thank CSIR, New Delhi
for the award of a Pool Officership to A. V. B., a Research
Associateship to A. S. G., a Senior Research Fellowship to
G. K. J., and we also thank the Lady Tata Memorial trust,
Mumbai, for a research fellowship to N. S. The award of a
research grant from DST under the Scheme for Young
Scientists (HR/OY/C-15/97) to AVB is immensely appreciated.
The gift of a sample of chloromethylated resin from Ion
Exchange (India) Ltd. is sincerely appreciated.
Yellow oil. [α]D ϩ5.66 (1.06, CHCl3); IR ν 3463, 3365, 2955,
1
1685, 1630, 1590, 1495, 1037, 753, 697 cmϪ1; H NMR δ 4.15
(m, 1H), 4.68 (m, 1H), 5.45 (m, 1H), 6.15 (br s, 2H), 6.70 (m
2H), 7.35 (m, 6H), 7.80 (d, J = 8.0 Hz, 1H); MS m/z (%) 238
(Mϩ, 94), 218 (8), 207 (48), 193 (3), 180 (10), 160 (25), 147 (18),
131 (28), 118 (96), 91 (55), 83 (100), 77 (37), 65 (20). Calcd. for
C15H14N2O: C, 75.63; H, 5.88; N, 11.76. Found: C, 75.17; H,
5.91; N, 11.20%.
2-(4-Ethyl-4,5-dihydro-1,3-oxazol-2-yl)aniline 8
References
Light yellow oil. [α]D Ϫ7.45 (1.45, CHCl3); IR ν 3440, 3290,
2948, 1660, 1450, 1052, 748 cmϪ1; 1H NMR δ 1.05 (t, J = 8.0 Hz,
3H), 1.55–1.85 (m, 2H), 3.85–4.00 (m, 1H), 4.20–4.45 (m, 2H),
6.20 (br s, 2H), 6.60–6.80 (m 2H), 7.22 (t, J = 8.0 Hz, 1H), 7.74
(d, J = 8.0 Hz, 1H); MS m/z (%) 190 (Mϩ, 91), 175 (100), 161
(45), 133 (40), 118 (76), 106 (60), 92 (20), 65 (13). Calcd. for
C11H14N2O: C, 69.53; H, 7.97; N, 13.99. Found: C, 69.47; H,
7.37; N, 14.73%.
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3535.
2-(1,3-Benzoxazol-2-yl)aniline 9
Dark viscous oil. IR ν 3481, 3370, 3013, 2942, 1686, 1482, 1293,
1
1243, 1156, 1100, 750 cmϪ1; H NMR δ 5.75 (br s, 2H), 7.20–
7.35 (m, 2H), 7.62–7.72 (m, 4H), 7.80–7.95 (m, 2H); MS
m/z (%) 210 (Mϩ, 3), 151 (81), 119 (100), 92 (55), 75 (2), 65
(12). Calcd. for C13H10N2O: C, 74.28; H, 4.76; N, 13.33. Found:
C, 74.48; H, 4.26; N, 13.61%.
2-(1,3-Benzothiazol-2-yl)aniline 10
Brown solid. Mp 164.3–166.0 ЊC; IR ν 3377, 3057, 3011, 2955,
9 M. J. McKennon, A. I. Meyers, K. Drauz and M. Schwarm, J. Org.
Chem., 1993, 58, 3568.
1
2921, 2855, 1685, 1580, 1297, 1210, 759, 741, 665 cmϪ1; H
NMR δ 5.85 (br s, 2H), 6.90–7.15 (m, 2H), 7.30–7.60 (m,
4H), 7.80–8.10 (m, 2H). MS m/z (%) 210 (Mϩ, 3), 151 (81),
119 (100), 92 (55), 75 (2), 65 (12). Calcd. for C13H10N2S: C,
69.03; H, 4.42; N, 12.39; S, 14.16. Found: C, 68.70; H, 4.21; N,
12.00; S, 14.60%.
Paper a908564e
J. Chem. Soc., Perkin Trans. 1, 2000, 999–1001
1001