Synthesis of 3ꢀfluoromethylꢀ2,1ꢀbenzisoxazoles
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 10, October, 2014
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: 8.09 (s, CF3). MS (EI, 70 eV), m/z (Irel (%)): 189 [M]+ (54),
120 [M – CF3]+ (100), 92 [M – CF3– CO]+ (49).
References
1ꢀ(2ꢀAminoꢀ5ꢀchlorophenyl)ꢀ2,2,2ꢀtrifluoroethanone (3b)
was synthesized similarly to compound 3a by hydrogenation of
5ꢀchloroꢀ3ꢀ(trifluoromethyl)ꢀ2,1ꢀbenzisoxazole (1b) in ethyl
acetate. Yield 82%. Yellow crystals. M.p. 91—92 C (pentane),
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1
cf. Ref. 20: 90—91 C. H NMR (600.22 MHz, CDCl3), : 7.76
(m, 1 H, H(6)); 7.38 (dd, 1 H, H(4), J1 = 9.0 Hz, J2= 2.3 Hz);
6.75 (d, 1 H, H(3), J = 9.0 Hz); 6.52 (br.s, 2 H, NH2). 13C NMR
(150.93 MHz, CDCl3), : 180.1 (q, C=O, 2JC,F = 34 Hz); 151.6,
4
136.9; 130.0 (q, C(6), JC,F = 4.4 Hz); 120.9, 119.0, 116.8
(q, CF3, 1JC,F = 291 Hz); 111.4. 19F NMR (282.38 MHz, CDCl3),
: 7.88 (s, CF3). MS (EI, 70 eV), m/z (Irel (%)): 223 [M]+ (55),
154 [M – CF3]+ (100), 126 [M – CF3 – CO]+ (41), 90 [M –
– CF3 – CO – HCl]+ (24).
1ꢀ(2ꢀAminoꢀ5ꢀbromophenyl)ꢀ2,2,2ꢀtrifluoroethanone (3c)
was synthesized similarly to compound 3a by hydrogenation of
5ꢀbromoꢀ3ꢀ(trifluoromethyl)ꢀ2,1ꢀbenzisoxazole 1c in ethyl acetꢀ
ate. Yield 80%. Yellow crystals. M.p. 100—102 C (pentane), cf.
1
Ref. 20: 100—101 C. H NMR (600.22 MHz, CDCl3), : 7.86
(m, 1 H, H(6)); 7.46 (dd, 1 H, H(4), J1 = 9.0 Hz, J2 = 2.3 Hz);
6.67 (d, 1 H, H(3), J = 9.0 Hz); 6.52 (br.s, 2 H, NH2). 13C NMR
(150.93 MHz, CDCl3), : 180.0 (q, C=O, 2JC,F = 34 Hz); 151.9,
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4
139.4; 133.1 (q, C(6), JC,F = 4.4 Hz); 119.3; 116.8 (q, CF3,
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1JC,F = 292 Hz), 112.1, 107.5. 19F NMR (282.38 MHz, CDCl3),
: 7.75 (s, CF3). MS (EI, 70 eV), m/z (Irel (%)): 267 [M]+ (50),
198 [M – CF3]+ (100), 170 [M – CF3 – CO]+ (40), 91 [M –
– CF3 – CO – Br]+ (26).
1ꢀ(2ꢀAminoꢀ5ꢀchlorophenyl)ꢀ2,2ꢀdifluoroethanone (3d) was
synthesized similarly to compound 3a by hydrogenation of
5ꢀchloroꢀ3ꢀ(difluoromethyl)ꢀ2,1ꢀbenzisoxazole 1d in ethyl acetate.
Product was purified by column chromatography (elution with
petroleum ether—ethyl acetate (6 : 1)). Yield 85%. Yellow crysꢀ
tals. M.p. 102—103 C (pentane). 1H NMR (600.22 MHz,
CDCl3), : 7.79 (s, 1 H, H(6)); 7.31—7.33 (m, 1 H, H(4)); 6.70
(d, 1 H, H(3), J = 8.8 Hz); 6.43 (s, 2 H, NH2); 6.30 (t, 1 H,
CF2H, J = 53.7 Hz). 13C NMR (150.93 MHz, CDCl3), : 184.8
2
(t, CO—CF2H, JC,F = 24 Hz); 148.3, 133.7; 127.4 (t, C(6),
4JC,F = 5 Hz); 118.1, 116.4, 110.6; 108.6 (t, CF2H, 1JC,F = 254 Hz).
2
19F NMR (282.38 MHz, CDCl3), : –42.90 (d, CF2H, JH,F
=
= 53.7 Hz). MS (EI, 70 eV), m/z (Irel (%)): 205 [M]+ (56), 154
[M – HCF2]+ (100), 126 [M – HCF2 – CO]+ (48), 90 [M –
–HCF2 – CO – HCl]+ (22). Found (%): C, 46.69; H, 3.03;
N, 6.65. C8H6ClF2NO. Calculated (%): C, 46.74; H, 2.94; N, 6.81.
1ꢀ(2ꢀAminoꢀ5ꢀbromophenyl)ꢀ2,2ꢀdifluoroethanone (3e) was
synthesized similarly to compound 3a by hydrogenation of
5ꢀbromoꢀ3ꢀ(difluoromethyl)ꢀ2,1ꢀbenzisoxazole 1e. The product
was purified by column chromatography (elution with petroꢀ
leum ether—ethyl acetate (6 : 1)). Yield 85%. Yellow crystals.
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1
M.p. 102—103 C (pentane). H NMR (600.22 MHz, CDCl3),
: 7.90 (br.s, 1 H, H(6)); 7.42 (dd, 1 H, H(4), J1 = 9.0 Hz,
J2 = 2.2 Hz); 6.64 (d, 1 H, H(3), J = 9.0 Hz); 6.43 (br.s, 2 H, NH2);
6.31 (t, 1 H, CF2H, J = 53.7 Hz). 13C NMR (150.93 MHz,
2
CDCl3), : 187.3 (t, CO—CF2H, JC,F = 24 Hz); 151.1, 138.9;
4
133.0 (t, C(6), JC,F = 5 Hz); 119.2, 113.9; 111.1 (t, CF2H,
1JC,F = 254 Hz); 107.2. 19F NMR (282.38 MHz, CDCl3),
2
: –42.88 (d, CF2H, JH,F = 53.7 Hz). MS (EI, 70 eV), m/z
(Irel (%)): 249 [M]+ (46), 198 [M – HCF2]+ (100), 170
[M – HCF2 – CO]+ (31), 91 [M – HCF2 – CO – Br]+ (20).
Found (%): C, 38.47; H, 2.51; N, 5.44. C8H6BrF2NO. Calculatꢀ
ed (%): C, 38.43; H, 2.42; N, 5.60.
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