Synthesis of New 2-­‐N,N’-­‐dialkylamino-­‐1,4-­‐naphthoquinone Derivatives: Concerning the Reactivity of Lapachol with Secondary Amines David, C. C.; Campos, J. F.; Silva, T. M. S.; Camara, C. A.* Rev. Virtual Quim., 2015, 7 (2), S1-­‐S33. Data de publicação na Web: 6 de janeiro de 2015 http://www.uff.br/rvq 55
LAP.NHMe(2)
15
577.7
551.5
952.7
728.1
1080.0
1276.2
1289.6
1309.7
1249.7
1453.0
1425.0
1419.1
693.9
669.6
1033.9
20
1563.5
3333.6
1671.4
25
1349.3
30
1598.9
3465.3
35
3086.3
3062.3
3027.9
2998.0
2954.9
2925.5
2892.4
3112.5
40
1144.4
1095.3
45
%Transmittance
849.1
789.7
50
1512.6
10
3800
3600
3400
3200
3000
2800
2600
2400
2200
2000
Wavenumber
1800
1600
1400
1200
1000
800
600
400
Figure S1. Infrared spectrum (KBr, cm-­‐1) of compound 1i 1 David, C. C. et al. Figure S2. 1H NMR spectrum (CDCl3, 400 MHz) of compound 1i Figure S3. 13C NMR (APT) spectrum (CDCl3, 100 MHz) of compound 1i 2 Intens. [a.u.]
LPC-NHMe 0:E19 MS Raw
257.1416
255.1252
800
256.1257
600
400
254.1193
200
0
248
250
252
254
256
258
260
262
264
266
m/z
Figure S4. High resolution mass spectra of compound 1i 42
M-1(2)
40
570
534
481
38
888
856
809
784
34
1161
717
963
1631
24
1114
1663
1594
2953
2905
2856
26
1250
1202
28
1408
1440
3073
3017
30
1065
1021
32
3442
%Transmittance
664
614
36
1284
22
1550
20
18
3800
3600
3400
3200
3000
2800
2600
2400
2200
2000
Wavenumber
1800
1600
1400
1200
1000
800
600
400
Figure S5. Infrared spectrum (KBr, cm-­‐1) of compound 5b 3 David, C. C. et al. Figure S6. 1H NMR spectrum (CDCl3, 400 MHz) of compound 5b Figure S7. 13C NMR (APT) spectrum (CDCl3, 100 MHz) of compound 5b 4 Intens. [a.u.]
M-1.3 0:P20 MS Raw
297.1350
2000
1500
1000
500
315.1437
0
220
240
260
280
300
320
340
360
380
400
m/z
Figure S8. High resolution mass spectra of compound 5b 58
M2(2)
585
54
666
52
50
515
476
430
56
782
48
1079
1020
996
44
717
42
40
3442
1415
30
1292
1631
32
1595
34
1666
3070
36
2963
2927
2907
2850
38
938
1250
1192
%Transmittance
46
1551
28
26
3800
3600
3400
3200
3000
2800
2600
2400
2200
2000
Wavenumber
1800
1600
1400
1200
1000
800
600
400
Figure S9. Infrared spectrum (KBr, cm-­‐1) of compound 5c 5 David, C. C. et al. 1
Figure S10. H NMR spectrum (CDCl3, 400 MHz) of compound 5c Figure S11. 13C NMR (APT) spectrum (CDCl3, 100 MHz) of compound 5c 6 Intens. [a.u.]
M-2 0:P16 MS Raw
313.1137
2500
2000
1500
1000
500
329.0989
0
150
200
250
300
350
400
m/z
Figure S12. High resolution mass spectra of compound 5c 52
M3(2)
50
48
569
521
44
664
42
454
46
852
24
1344
1253
1442
1408
1305
1289
2930
26
1667
1626
28
2852
3434
30
1596
3074
3018
32
716
34
957
1126
36
1054
1023
809
38
1214
1156
%Transmittance
40
1548
22
20
3800
3600
3400
3200
3000
2800
2600
2400
2200
2000
Wavenumber
1800
1600
1400
1200
1000
800
600
400
Figure S13. Infrared spectrum (KBr, cm-­‐1) of compound 5d 7 David, C. C. et al. 1
Figure S14. H NMR spectrum (CDCl3, 400 MHz) of compound 5d Figure S15. 13C NMR (APT) spectrum (CDCl3, 100 MHz) of compound 5d 8 Figure S16. COSY spectrum of compound 5d Figure S17. HMBC spectrum of compound 5d
9 David, C. C. et al. Intens. [a.u.]
M-3.2 0:N22 MS Raw
295.1553
3000
2000
1000
312.1539
0
275
280
285
290
295
300
305
310
315
320
m/z
Figure S18. High resolution mass spectra of compound 5d 64
M-4(2)
433
407
62
58
800
56
719
1086
1214
1163
1141
1258
48
1343
50
1004
965
1446
1416
%Transmittance
54
52
487
666
625
60
44
3013
2964
2924
2882
2846
1555
42
40
3447
38
1290
1665
1629
1596
46
3800
3600
3400
3200
3000
2800
2600
2400
2200
2000
Wavenumber
1800
1600
1400
1200
Figure S19. Infrared spectrum (KBr, cm-­‐1) of compound 5e 10 1000
800
600
400
1
Figure S20. H NMR spectrum (CDCl3, 400 MHz) of compound 5e Figure S21. 13C NMR (APT) spectrum (CDCl3, 100 MHz) of compound 5e 11 David, C. C. et al. Intens. [a.u.]
x104
M-4 0:N19 MS Raw
310.1658
2.0
1.5
1.0
311.1674
308.1468
0.5
309.1537
307.1354
305.1199
0.0
304
306
308
310
312
314
316
318
320
322
m/z
Figure S22. High resolution mass spectra of compound 5e 58
NORL.NHMe(2)
56
36
1514.709
32
3350.521
30
596.020
531.226
659.167
681.765
1281.720
1571.823
34
1300.434
38
1596.804
1666.197
40
28
723.521
1419.771
1332.436
42
1351.240
44
3435.534
%Transmittance
46
1624.005
48
1380.535
3068.578
3016.490
2974.331
2929.377
50
921.983
1160.124
1082.047 1100.557
1027.527
52
799.456
54
26
3800
3600
3400
3200
3000
2800
2600
2400
2200
2000
Wavenumber
1800
1600
1400
1200
Figure S23. Infrared spectrum (KBr, cm-­‐1) of compound 5i 12 1000
800
600
400
1
Figure S24. H NMR spectrum (CDCl3, 400 MHz) of compound 5i Figure S25. 13C NMR (APT) spectrum (CDCl3, 100 MHz) of compound 5i 13 David, C. C. et al. Intens. [a.u.]
NLP-NHMe.3 0:P23 MS Raw
257.1442
2000
256.1246
1500
229.1085
1000
249.1300
241.1101
500
268.1180
264.1509
251.1246
238.0889
255.1479
244.1078
0
225
230
235
240
245
250
255
260
265
270
m/z
Figure 26. High resolution mass spectra of compound 5i 56
NORL.NMe2(5)
54
508.7
3431.8
36
34
3800
3600
3400
3200
3000
2800
2600
2400
2200
2000
Wavenumber
1800
1600
1400
1200
Figure S27. Infrared spectrum (KBr, cm-­‐1) of compound 5j 14 724.2
966.1
1439.1
1554.9
1670.0
1628.1
1594.6
38
2856.8
40
2961.8
2924.7
3079.7
42
1381.5
1349.9
1328.7
1304.3
44
1040.7
1166.8
46
1278.5
%Transmittance
48
587.0
792.7
50
667.4
613.9
52
1000
800
600
400
1
Figure S28. H NMR spectrum (CDCl3, 400 MHz) of compound 5j Figure S29. 13C NMR (APT) spectrum (CDCl3, 100 MHz) of compound 5j 15 David, C. C. et al. Intens. [a.u.]
NLP-NMe2 0:A20 MS Raw
244.0993
800
600
257.1313
400
200
255.1206
0
245
250
255
260
265
270
275
m/z
Figure 30. High resolution mass spectra of compound 5j 60
58
N1(2)
56
576
530
504
455
54
52
661
50
840
934
48
40
729
785
1392
42
38
1567
24
983
1210
1677
1645
26
1119
1592
3459
28
1305
3070
3037
30
2974
2927
2873
32
1341
34
1246
1274
36
22
3800
3600
3400
3200
3000
2800
2600
2400
2200
2000
Wavenumber
1800
1600
1400
1200
Figure S31. Infrared spectrum (KBr, cm-­‐1) of compound 6b 16 872
1162
44
1440
%Transmittance
46
1000
800
600
400
1
Figure S32. H NMR spectrum (CDCl3, 400 MHz) of compound 6b Figure S33. 13C NMR (APT) spectrum (CDCl3, 100 MHz) of compound 6b
17 David, C. C. et al. Intens. [a.u.]
x104
N-1 0:N16 MS Raw
243.090776
5
4
3
2
1
185.038447
229.106966
257.144126
0
80
100
120
140
160
180
200
220
240
260
m/z
Figure S34. High resolution mass spectra of compound 6b 60
N2(3)
55
646
40
489
45
580
419
50
1678
1624
1590
1561
5
0
3600
3400
3200
3000
2800
2600
2400
2200
2000
Wavenumber
1800
1600
1400
1200
Figure S35. Infrared spectrum (KBr, cm-­‐1) of compound 6c 18 783
725
1027
1337
13051283
1234
1191
10
3800
1160
1120
1439
2843
1411
3495
15
3066
3006
2966
2922
20
946
25
854
808
994
30
1477
%Transmittance
35
1000
800
600
400
1
Figure S36. H NMR spectrum (CDCl3, 400 MHz) of compound 6c Figure S37. 13C NMR (APT) spectrum (CDCl3, 100 MHz) of compound 6c
19 David, C. C. et al. Intens. [a.u.]
N-2.2 0:L22 MS Raw
259.0692
800
600
400
200
0
256
258
260
262
264
266
m/z
Figure S38. High resolution mass spectra of compound 6c N3(2)
40
727
783
973
1218
1561
1242
10
1339
1302
1677
1628
1590
15
1126
1447
2936
20
5
3800
3600
3400
3200
3000
2800
2600
2400
2200
2000
Wavenumber
1800
1600
1400
1200
Figure S39. Infrared spectrum (KBr, cm-­‐1) of compound 6d 20 858
1086
1044
1156
1477
2855
2823
25
1399
3068
3017
30
809
3451
%Transmittance
35
503
470
451
652
45
1000
800
600
400
1
Figure S40. H NMR spectrum (CDCl3, 400 MHz) of compound 6d Figure S41. 13C NMR (APT) spectrum (CDCl3, 100 MHz) of compound 6d
21 David, C. C. et al. Intens. [a.u.]
x104
N-3 0:L19 MS Raw
241.1119
4
3
2
1
229.1074
256.1235
0
215
220
225
230
235
240
245
250
255
260
265
m/z
Figure S42. High resolution mass spectra of compound 6d N4(3)
667
858
10
3800
3600
3400
3200
3000
2800
2600
2400
2200
2000
Wavenumber
1800
1600
1400
1200
Figure S43. Infrared spectrum (KBr, cm-­‐1) of compound 6e 22 982
1122
1208
1147
1339
1562
1642
15
1242
1673
1592
20
775
727
1080
836
1477
1443
2762
2888
2844
2804
2929
25
2961
3068
3042
30
3467
%Transmittance
35
1295
40
612
45
516
453
50
1000
800
600
400
1
Figure S44. H NMR spectrum (CDCl3, 400 MHz) of compound 6e Figure S45. 13C NMR (APT) spectrum (CDCl3, 100 MHz) of compound 6e
23 David, C. C. et al. Intens. [a.u.]
x104
N-4 0:L16 MS Raw
256.1205
2.5
2.0
1.5
1.0
257.1278
0.5
0.0
252
254
256
258
260
262
264
266
m/z
Figure S46. High resolution mass spectra of compound 6e 40
N6(3)
38
36
574
32
22
6
1000
1243
1354
1331
1298
8
1619
2965
10
1675
2933
2873
12
1592
3067
3450
14
1468
1425
16
1213
1150
18
773
1126
1092
20
722
1038
24
%Transmittance
752
894
26
827
28
663
30
470
34
4
1554
2
0
3800
3600
3400
3200
3000
2800
2600
2400
2200
2000
Wavenumber
1800
1600
1400
1200
Figure S47. Infrared spectrum (KBr, cm-­‐1) of compound 6f 24 1000
800
600
400
1
Figure S48. H NMR spectrum (CDCl3, 400 MHz) of compound 6f Figure S49. 13C NMR (APT) spectrum (CDCl3, 100 MHz) of compound 6f
25 David, C. C. et al. N7(2)
727
965
904
40
836
633
45
1010
784
1071
1218
1145
1380
1332
1306
1442
1620
1587
25
1676
2977
3479
2963
2936
30
1464
3064
3025
35
%Transmittance
520
469
50
1256
20
1558
15
10
3800
3600
3400
3200
3000
2800
2600
2400
2200
2000
Wavenumber
1800
1600
1400
1200
1000
800
600
400
Figure S50. Infrared spectrum (KBr, cm-­‐1) of compound 6g Figure S51. 1H NMR spectrum (CDCl3, 400 MHz) of compound 6g
26 Intens. [a.u.]
Figure S52. 13C NMR (APT) spectrum (CDCl3, 100 MHz) of compound 6g x104
N-7 0:J19 MS Raw
229.1103
2.0
1.5
1.0
0.5
256.1241
245.1073
214.0806
0.0
200
220
240
260
280
300
320
340
360
m/z
Figure S53. High resolution mass spectra of compound 6g 27 David, C. C. et al. 52
N8(2)
50
592
46
556
44
40
816
38
32
1242
1210
1410
1670
22
20
1634
18
1333
1302
24
1592
3445
26
2980
28
2911
2860
3085
3060
30
786
1478
1164
1122
1063
1009
964
927
902
34
724
853
36
704
42
%Transmittance
506
460
48
16
1560
14
12
3800
3600
3400
3200
3000
2800
2600
2400
2200
2000
Wavenumber
1800
1600
1400
1200
1000
800
600
-­‐1
Figure S54. Infrared spectrum (KBr, cm ) of compound 6h Figure S55. 1H NMR spectrum (CDCl3, 400 MHz) of compound 6h. 28 400
13
Figure S56. C NMR (APT) spectrum (CDCl3, 100 MHz) of compound 6h Figure S57. COSY spectrum of compound 6h.
29 David, C. C. et al. Figure S58. HMQC spectrum of compound 6h Figure S59. HMBC spectrum of compound 6h.
30 Intens. [a.u.]
N-8 0:J16 MS Raw
255.1283
5000
4000
3000
2000
253.1093
1000
254.1178
0
250
252
254
256
258
260
262
264
m/z
Figure 60. High resolution mass spectra of compound 6h 726
3376
3346
50
1123
1072
1220
1427
1678
55
1359
1334
1306
1255
60
2820
3067
3010
65
2924
2894
70
%Transmittance
671
842
947
75
503
454
LAUSNHMe(2)
780
80
1502
45
1567
40
35
1608
30
25
3800
3600
3400
3200
3000
2800
2600
2400
2200
2000
Wavenumber
1800
1600
1400
1200
1000
800
600
400
Figure S61. Infrared spectrum (KBr, cm-­‐1) of compound 6i. 31 David, C. C. et al. 1
Figure 62. H NMR spectrum (DMSO-­‐d6, 90 MHz) of compound 6i -­‐1
Figure 63. IR (KBr, cm ) of compound 6j. 32 1
Figure 64. H NMR spectrum (CDCl3, 90 MHz) of compound 6j Figure S65. 13C NMR spectrum (CDCl3, 22.73 MHz) of compound 6j 33