ꢀꢀꢀꢁ
60ꢀ ꢀD. Schulze et al.: BOX A-type monopyrrolic heterocycles modified via the Suzuki-Miyaura reaction
the remaining aqueous phase extracted three times with
10 mL of ethyl acetate. The combined organic phases were
washed with 10 mL of a saturated NaCl solution and dried
over anhydrous Na2SO4. After filtration, the solvent of the
filtrate was removed in vacuo. Purity was checked by NMR
spectroscopy and the acids 6h and 6i were used for trans-
formations without further purification.
4.4 General procedure for
3-(4-trifluoromethylphenyl)- and
3-(3,5-bis(trifluoromethyl)phenyl)-
substituted methyl (Z)-2-(4-methyl-5-
oxo-1,5-dihydro-2H-pyrrol-2-ylidene)
acetyl chlorides (7h and 7i)
Physical data of 6h: Yield: 175 mg (0.59 mmol, 92%).
A drop of DMF and 1.3 equivalents of DCM were added at
r. t. to a solution of the acetic acids 6h and 6i. After stir-
ring for 2 h and ceased gas evolution the volatiles were
removed in vacuo. The remaining solid was dried in vacuo
and these products 7h and 7i were used for the final con-
version without further purification.
– 1H NMR (400.13 MHz, DMSO-d6, 296 K): δꢀ=ꢀ12.68 (s, br,
3
1H, COOH), 10.04 (s, 1H, NH), 7.89 (d, JH,Hꢀ=ꢀ8.1 Hz, 2H,
3
m-CHpCF3Ph), 7.62 (d, JH,Hꢀ=ꢀ8.0 Hz, 2H, o-CHpCF3Ph), 5.03 (s,
1H, CH), 1.88 (s, 3H, CH3). – 13C{1H} NMR (100.61 MHz,
DMSO-d6, 296 K): δꢀ=ꢀ170.5 (CONH), 167.2 (COOH), 148.9
5
(C=CH), 142.3 (C−C6H4CF3), 134.5 (d, JC,Fꢀ=ꢀ1.4 Hz, ipso-
Physical data of 7h: Yield: 170 mg (0.54 mmol, 95%),
C
pCF3Ph), 133.5 (C−CH3), 130.2 (s, o-CHpCF3Ph), 129.3 (q,
1
light brown solid. – H NMR (400.13 MHz, [D8]THF,
3
2JC,Fꢀ=ꢀ32.0 Hz, C−CF3), 125.7 (q, JC,Fꢀ=ꢀ3.7 Hz, m-CHpCF3Ph),
3
297 K): δꢀ=ꢀ10.24 (s, br, 1H, NH), 7.85 (d, JH,Hꢀ=ꢀ8.2 Hz, 2H,
1
19
124.1 (q, JC,Fꢀ=ꢀ272.3 Hz, CF3), 97.4 (C=CH), 9.2 (CH3). – F
NMR (376.58 MHz, DMSO-d6, 297 K): δꢀ=ꢀ−ꢀ61.21 (s, CF3). –
IR (ATR): 3416 (w), 3268 (w), 3219–2231 (m, br), 2929 (m),
1726 (m), 1707 (m), 1676 (m), 1643 (m), 1618 (m), 1450 (m),
1409 (m), 1382 (w), 1356 (m), 1322 (s), 1296 (m), 1253 (m),
1229 (m), 1206 (m), 1167 (m), 1110 (s), 1067 (m), 1018 (m),
995 (m), 948 (m), 842 (m), 776 (m), 761 (m), 743 (m), 695
(m), 670 (m), 635 (m), 617 (m), 578 (m), 535 (m), 491 (m),
3
m-CHpCF3Ph), 7.58 (d, JH,Hꢀ=ꢀ8.1 Hz, 2H, o-CHpCF3Ph), 5.40 (s,
1H, CH), 1.95 (s, 3H, CH3). – 13C{1H} NMR (100.61 MHz, [D8]
THF, 297 K): δꢀ=ꢀ171.8 (CONH), 164.4 (COCl), 153.8 (C=CH),
143.8 (C−C6H4CF3), 136.8 (C−CH3), 135.0 (ipso-CpCF3Ph), 131.9
2
(q, JC,Fꢀ=ꢀ32.4 Hz, C−CF3), 130.9 (s, o-CHpCF3Ph), 126.7 (q,
3JC,Fꢀ=ꢀ3.8 Hz, m-CHpCF3Ph), 125.1 (q, 1JC,Fꢀ=ꢀ272.2 Hz, CF3), 100.4
(C=CH), 9.4 (CH3). – 19F NMR (376.58 MHz, [D8]THF, 297 K):
+
δꢀ=ꢀ−ꢀ63.60 (s, CF3). – MS (DEI): m/z (%)ꢀ=ꢀ315 (41) [M] , 280
+
458 (m), 441 (m). – MS (DEI): m/z (%)ꢀ=ꢀ297 (100) [M] ,
+
(100) [M–Cl] .– HRMS (EI): m/zꢀ=ꢀ315.0279 (calcd. 315.0274
+
+
280 (11) [M–OH] , 269 (36) [M–CO] , 251 (22) [M–H2O–
+
for C14H9ClF3NO2, [M] .
+
+
+
CO] , 225 (60) [Mꢀ+ꢀH–COOH–CO] , 154 (28) [C11H8N] , 115
(21) [C9H7] . – Elemental analysis (C14H10F3NO3, 297.23):
Physical data for 7i: Yield: 160 mg (0.42 mmol, 99%),
+
1
brown solid. – H NMR (400.13 MHz, [D8]THF, 297 K):
calcd.: C 56.57, H 3.39, N 4.71; found C 56.68, H 3.83,
N 4.27.
δꢀ=ꢀ10.34 (s, br, 1H, NH), 8.19 (s, 1H, p-CHm(CF3)2Ph), 8.02 (s,
2H, o-CHm(CF3)2Ph), 5.37 (s, 1H, CH), 1.94 (s, 3H, CH3). – 13C{1H}
NMR (100.61 MHz, [D8]THF, 297 K): δꢀ=ꢀ171.5 (CONH), 164.4
(COCl), 153.4 (C=CH), 142.5 (C−C6H3(CF3)2), 138.0 (C−CH3),
Physical data of 6i: Yield: 192 mg (0.53 mmol, 99%),
1
pale yellow solid. – H NMR (400.21 MHz, DMSO-d6,
297 K): δꢀ=ꢀ12.70 (s, br, 1H, COOH), 10.10 (s, 1H, NH),
8.24 (s, 1H, p-CHm(CF3)2Ph), 8.12 (s, 2H, o-CHm(CF3)2Ph), 4.97
(s, 1H, CH), 1.87 (s, 3H, CH3). – 13C{1H} NMR (100.63 MHz,
DMSO-d6, 297 K): δꢀ=ꢀ170.2 (CONH), 167.1 (COOH), 148.7
(C=CH), 140.9 (C−C6H3(CF3)2), 134.7 (C−CH3), 133.0
2
133.7 (ipso-Cm(CF3)2Ph), 133.0 (q, JC,Fꢀ=ꢀ33.5 Hz, C−CF3), 130.8
(q, 3JC,Fꢀ=ꢀ3.9 Hz, o-CHm(CF3)2Ph), 124.3 (q, 1JC,Fꢀ=ꢀ272.7 Hz, CF3),
124.1 (q, 3JC,Fꢀ=ꢀ3.6 Hz, p-CHm(CF3)2Ph), 100.6 (C=CH), 9.4 (CH3).
– 19F NMR (376.58 MHz, [D8]THF, 297 K): δꢀ=ꢀ−ꢀ65.52 (s, CF)3.
+
+
– MS (DEI): m/z (%)ꢀ=ꢀ383 (19) [M] , 348 (100) [M–Cl] .
2
(ipso-Cm(CF3)2Ph), 130.8 (q, JC,Fꢀ=ꢀ33.2 Hz, C−CF3), 130.2 (d,
1
3JC,Fꢀ=ꢀ3.1 Hz, o-CHm(CF3)2Ph), 123.1 (q, JC,Fꢀ=ꢀ273.1 Hz, CF3),
122.8 (q, 3JC,Fꢀ=ꢀ3.6 Hz, p-CHm(CF3)2Ph), 97.5 (C=CH), 9.2 (CH3).
4.5 General procedure for
–
19F NMR (376.58 MHz, DMSO-d6, 297 K): δꢀ=ꢀ−61.20 (s,
3-(4-trifluoromethylphenyl)- and
3-(3,5-bis(trifluoromethyl)phenyl)-
substituted methyl (Z)-2-(4-methyl-5-
oxo-1,5-dihydro-2H-pyrrol-2-ylidene)
acetamides (8h and 8i)
CF3). – IR (ATR): 3271 (w), 3215–2285 (w, br), 2927 (w),
1706 (m), 1679 (m), 1651 (m), 1468 (m), 1439 (m), 1404
(m), 1379 (m), 1322 (m), 1276 (s), 1213 (m), 1167 (s), 1124
(s), 1032 (m), 903 (m), 885 (m), 847 (m), 832 (m), 760
(m), 706 (m), 681 (s), 644 (m), 628 (m), 576 (m), 509 (m),
+
443 (m), 417 (m). – MS (DEI): m/z (%)ꢀ=ꢀ365 (100) [M] ,
+
+
348 (22) [M–OH] , 337 (29) [M–CO] , 319 (22) [M–H2O– Ammonia was passed into a solution of the acetyl chlo-
+
+
CO] , 293 (72) [Mꢀ+ꢀH–COOH–CO] . – Elemental analy- rides 7h and 7i in anhydrous THF at 0°C. After 30 min
sis (C15H9F6NO3, 365.23): calcd.: C 49.33, H 2.48, N 3.84; the cooling bath was removed and ammonia was passed
found C 49.83, H 3.07, N 3.38.
into this reaction mixture for approximately an additional
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