Supporting Information · S2 Optimization of Reaction Conditions of N-Ethylation of Benzamide 2a...

S1

Supporting Information

Bis(trialkylsilyl) peroxides as alkylating agents in the

copper-catalyzed selective mono-N-alkylation of primary amides

Ryu Sakamoto Shunya Sakurai and Keiji Maruoka

Laboratory of Synthetic Organic Chemistry and Special Laboratory of Organocatalytic Chemistry Department of Chemistry Graduate School of Science Kyoto University

Sakyo Kyoto 606-8502 Japan

General Information

1H NMR spectra were measured on JEOL JNM-ECA500 (500 MHz) spectrometer Data

were reported as follows chemical shifts in ppm from tetramethylsilane as an internal

standard in CDCl3 integration multiplicity (s = singlet d = doublet t = triplet q = quartet

m = multiplet br = broad) coupling constants (Hz) and assignment 13C NMR spectra

were measured on JEOL JNM-ECA500 (125 MHz) spectrometer with complete proton

decoupling Chemical shifts were reported in ppm from the residual solvent as an internal

standard 29Si NMR spectra were measured on JEOL JNM-ECA500 (100 MHz)

spectrometer Infrared (IR) spectra were recorded on a Thermo Scientific Nicolet iS5

spectrometer High-resolution mass spectra (HRMS) were performed on Thermo

Exactive plus The products were purified by flash column chromatography (silica gel 60

Merck 230-400 mesh) or preparative thin layer chromatography silica gel (PLC 60 F254

05 mm) Commercially available reagents were purchased from Wako Sigma-Aldrich

TCI and Alfa-aesar chemicals and used as received Benzene was used after the

distillation from CaH2

Electronic Supplementary Material (ESI) for Chemical CommunicationsThis journal is copy The Royal Society of Chemistry 2017

S2

Optimization of Reaction Conditions of N-Ethylation of Benzamide 2a with 1a

Table S1 The effect of the amount of peroxide [a]

[a] Reaction conditions bezamide 2a (01 mmol 10 eq) 1a (X eq) CuI (10

mol) L1 (10 mol) benzene (025 mL 04 M) 100 degC 24 h [b] Yield was

determined by 1H NMR spectroscopy using DMF as an internal standard [c]

1a (02 mmol 20 eq) was added to the reaction mixture after stirring for 1h

Table S2 The effect of the amount of catalyst and ligand [a]

[a] Reaction conditions bezamide 2a (01 mmol 10 eq) 1a (02 mmol

20 eq) CuI (X mol) bipyrimidine (X mol) benzene (025 mL 04

M) 100 degC 24 h [b] Yield was determined by 1H NMR spectroscopy

using DMF as an internal standard

Entry X 3a () [b] 2a () [b]

1 10 37 56

2 20 60 23

3 30 66 24

4 [c] 20+20 81 4

Entry X Yield of 3a () [b]

1 5 55

2 10 60

3 20 62

S3

Table S3 The effect of ligand [a]


20 eq) CuI (10 mol) ligand (10 mol) benzene (025 mL 04 M)

100 degC 24 h [b] Yield was determined by 1H NMR spectroscopy using

DMF as an internal standard

Entry Ligand Yield of 3a () [b]

1 none 45

2 L1 60

3 L2 71

4 L3 61

5 L4 71

6 L5 57

7 L6 50

8 L7 53

9 L8 39

10 L9 0

11 L10 44

12 L11 38

S4

General Procedure for the Synthesis of Bis(trialkylsilyl) Peroxide (1)

To a solution of 14-diazabicyclo[222]octane (112 g 100 mmol 10 eq) and H2O2

urea complex (941 mg 100 mmol 10 eq) in dry dichloromethane (20 mL) was added a

trialkylsilyl chloride (10 eq) slowly at 0 ˚C under argon atmosphere After 3 h of stirring

at room temperature to the reaction mixture was added pentane (20 mL) and the white

precipitate was removed by filtration Solvent was evaporated and the residue was

purified by flash column chromatography on silica gel (eluting with pentane) to afford a

corresponding product

Bis(triethylsilyl) peroxide (1a) [1]

Colorless oil 1H NMR (500 MHz CDCl3) δ 098 (18H t J = 79 Hz CH3) 068

(12H q J = 79 Hz SiCH2) 13C NMR (125 MHz CDCl3) δ 692

401 29Si NMR (100 MHz CDCl3) δ 2862

Bis(trimethylsilyl) peroxide (1b) [2]

Colorless oil 1H NMR (500 MHz CDCl3) δ 019 (18H s SiCH3)

13C NMR (125

MHz CDCl3) δ ndash116 29Si NMR (100 MHz CDCl3) δ 2786

Bis(tributylsilyl) peroxide (1c)

Colorless oil 1H NMR (500 MHz CDCl3) δ 135-132 (24H m) 089

(18H t J = 68 Hz CH3) 069-065 (12H m SiCH2) 13C NMR (125 MHz CDCl3) δ 267 256 139 128

29Si NMR (100 MHz CDCl3) δ 2651 HRMS calculated for C24H54O2NaSi2 mz

4533555 ([M + Na]+) found mz 4533545 ([M + Na]+) IR (neat) 2956 2922 1465

1195 1081 884 782 cm1

Bis(dimethylisopropylsilyl) peroxide (1d)

Colorless oil 1H NMR (500 MHz CDCl3) δ 098-097 (14H m) 012 (12H s

SiCH3) 13C NMR (125 MHz CDCl3) δ 172 139 ndash482 29Si NMR

(100 MHz CDCl3) δ 2884 HRMS calculated for C10H26O2NaSi2 mz 2571364 ([M +

Na]+) found mz 2571360 ([M + Na]+) IR (neat) 2944 2867 1463 1249 1000 813

778 cm1

S5

Bis(dicyclohexylmethylsilyl) peroxide (1e)

Colorless oil 1 H NMR (500 MHz CDCl3) δ 173-166 (10H m CH2)

123-112 (10H m CH2) 085-080 (2H m CH2) 012 (12H

m SiCH3) 13C NMR (125 MHz CDCl3) δ 281 280

271270 259 ndash141 ndash446 29Si NMR (100 MHz CDCl3) δ 2688 HRMS calculated

for C16H34O2NaSi2 mz 3371990 ([M + Na]+) found mz 3371983 ([M + Na]+) IR

(neat) 2918 2848 1446 1247 818 778 cm1

Bis(tert-butyldimethylmethylsilyl) peroxide (1f)

Colorless oil 1H NMR (500 MHz CDCl3) δ 093 (18H s CH3) 014 (12H s




725 cm1

General Procedure for Mono-N-Alkylation of Amide (2) with Disilyl Peroxide (1)

To a solution of amide 2 (02 mmol 10 eq) CuI (38 mg 10 mol) and 110-

phenanthroline (36 mg 10 mol) in benzene (05 mL) was added disilyl peroxide 1 (04

mmol 20 eq) under argon atmosphere The reaction mixture was stirred at 100 ˚C for 1

h After cooling to room temperature the reaction mixture was quenched with H2O

extracted with Et2O for three times The combined organic layer was washed with brine

dried over Na2SO4 and concentrated The residue was purified by flash column

chromatography on silica gel (eluting with ethyl acetatehexane = 23) to afford a


N-Ethylbenzamide (3a) [3]

White solid 186 mg 62 yield 1H NMR (500 MHz CDCl3) δ 777-775 (2H ) 749-747 (1H m

ArH) 744-740 (2H m ArH) 614 (1H br NH) 353-347 (2H m

NCH2) 125 (3H t J = 74 Hz CH3) 13C NMR (125 MHz CDCl3) δ

1676 1349 1315 1287 1270 351 150

S6

N-Methylbenzamide (3b) [4]

Me3SiO-OSiMe3 (1b) (40 eq) was used for the reaction

White solid 100 mg 37 yield 1H NMR (500 MHz CDCl3) δ 776-775 (2H m ArH) 751-748 (1H

m ArH) 744-741 (2H m ArH) 613 (1H br NH) 302 (3H d NCH3

J = 48 Hz) 13C NMR (125 MHz CDCl3) δ 1685 1348 1315 1287 1270 270

N-Butylbenzamide (3c) [5]

nBu3SiO-OSinBu3 (1c) (40 eq) was used for the reaction

White solid 202 mg 57 yield 1H NMR (500 MHz CDCl3) δ 776-775 (2H m ArH) 751-

747 (1H m ArH) 744-741 (2H m ArH) 608 (1H br NH)

349-345 (2H m NCH2) 162-158 (2H m CH2) 145-140 (2H m CH2) 097 (3H t

J = 74 Hz CH3) 13C NMR (125 MHz CDCl3) δ 1677 1348 1310 1282 1270 398

316 201 137

N-Isopropylbenzamide (3d) [6]


m ArH) 744-741 (2H m ArH) 589 (1H br NH) 433-426 (1H

m NCH) 127 (6H d J = 65 Hz CH3) 13C NMR (125 MHz CDCl3)

δ 1668 1352 1314 1287 1269 420 230

N-Cyclohexylbenzamide (3e) [7]

White solid 248 mg 61 yield 1H NMR (500 MHz CDCl3) δ 776-774 (2H m ArH) 749-747

(1H m ArH) 744-742 (2H m ArH) 594 (1H br NH) 402-396

(1H m NCH) 206-202 (2H m CH2) 177-174 (2H m CH2)

168-164 (1H m CH2) 148-140 (2H m CH2) 128-120 (3H m CH2) 13C NMR (125

MHz CDCl3) δ 1668 1353 1314 1287 1270 488 334 257 251

4-Chloro-N-ethylbenzamide (4a) [8]

Pale yellow solid 232 mg 63 yield 1H NMR (500 MHz CDCl3) δ 771-769 (2H m ArH) 741-739

(2H m ArH) 603 (1H br NH) 352-347 (2H m NCH2) 126

(3H t J = 74 Hz CH3) 13C NMR (125 MHz CDCl3) δ 1665

1377 1333 1289 1284 352 150

S7

4-Bromo-N-ethylbenzamide (4b) [9]




1338 1319 1286 1261 352 150

4-Acetoxy-N-ethylbenzamide (4c)

Et3SiO-OSiEt3 (1a) (40 eq) was used for the reaction

White solid 199 mg 48 yield 1H NMR (500 MHz CDCl3) δ 778 (2H d J = 88 Hz ArH)

716 (2H d J = 88 Hz ArH) 600 (1H br NH) 353-347

(2H m NCH2) 232 (3H s CH3) 125 (3H t J = 74 Hz CH3) 13C NMR (125 MHz

CDCl3) δ 1692 1667 1531 1326 1284 1219 351 213 150 HRMS calculated for

C11H13O3NNa mz 2300788 ([M + Na]+) found mz 2300787 ([M + Na]+) IR (neat)

3305 2921 1749 1634 1540 1255 1198 cm1

N-Ethyl-4-methoxybenzamide (4d) [8]


691 (2H m ArH) 598 (1H br NH) 385 (1H s OCH3) 352-

346 (2H m NCH2) 125 (3H t J = 74 Hz CH3) 13C NMR

(125 MHz CDCl3) δ 1671 1622 1287 1273 1139 555 350 152

N-Ethyl-4-methylbenzamide (4e) [8]


723 (2H d J = 82 Hz ArH) 603 (1H br NH) 352-347 (2H

m NCH2) 239 (3H s ArCH3) 125 (3H t J = 71 Hz CH3) 13C NMR (125 MHz CDCl3) δ 1675 1418 1321 1293 1270 350 216 151

N-Ethyl-2-methylbenzamide (4f) [9]



m NCH2) 245 (3H s ArCH3) 125 (3H t J = 74 Hz CH3) 13C

NMR (125 MHz CDCl3) δ 1702 1369 1361 1311 1299 1267 1258 348 198

151

S8

N-Ethyl-23456-pentafluorobenzamide (4g)

White solid 301 mg 63 yield 1H NMR (500 MHz CDCl3) δ 588 (1H br NH) 355-349 (2H

m NCH2) 127 (3H t J = 74 Hz CH3) 13C NMR (125 MHz

CDCl3) δ 1573 1453(m) 1433-1432 (m) 1413 (m) 1389-

1387 (m) 1369-1367 (m) 355 147 HRMS calculated for

C9H6ONF5Na mz 2620262 ([M + Na]+) found mz 2620263 ([M + Na]+) IR (neat)

1655 1502 1326 1265 991 735 cm1

N-Ethyl-2-furancarboxamide (4h) [8]

Pale yellow oil 148 mg 53 yield 1H NMR (500 MHz CDCl3) δ 742-741 (1H m ArH) 710-709 (1H

m ArH) 650-648 (1H m ArH) 632 (1H br NH) 350-344 (2H m


1584 1483 1437 1138 1121 341 150

(E)-N-Ethyl-3-phenyl-2-propenamide (4i)

White solid 140 mg 40 yield 1H NMR (500 MHz CDCl3) δ 762 (1H d J = 156 Hz CH)

751-749 (2H m ArH) 737-734 (3H m ArH) 637 (1H d J

= 156 Hz CH) 555 (1H br NH) 347-341 (2H m NCH2)

122 (3H t J = 74 Hz CH3) 13C NMR (125 MHz CDCl3) δ 1660 1409 1351 1297

1289 1279 1211 347 150 HRMS calculated for C11H13ONNa mz 1980889 ([M +


977 cm1

N-Ethyl-3-phenylpropanamide (4j) [10]

Et3SiO-OSiEt3 (1a) (20 eq) was added to the reaction mixture

after 1 h of stirring at 100 ˚C and then the reaction mixture was

stirred at 100 ˚C for another 1 h

White solid 181 mg 51 yield 1H NMR (500 MHz CDCl3) δ 730-727 (2H m ArH) 721-719 (3H m ArH) 529

(1H br NH) 327-324 (2H m NCH2) 296 (2H t J = 74 Hz CH2) 245 (2H t J =

79 Hz CH2) 106 (3H t J = 74 Hz CH3) 13C NMR (125 MHz CDCl3) δ 1720 1411

1286 1285 1263 387 344 319 149

Benzyl N-ehylcarbamate (4k) [11]

White solid 169 mg 47 yield 1H NMR (500 MHz CDCl3) δ 739-729 (5H m ArH) 510

(2H s OCH2) 468 (1H br NH) 327-322 (2H m NCH2) 115


1367 1285-1280(3 peaks overlap) 665 359 152

S9

1-Ethyl-3-phenylurea (4l) [12]


(2H m ArH) 712-710 (1H m ArH) 617 (1H br NH) 463 (1H

br NH) 333-328 (2H m NCH2) 116 (3H t J = 71 Hz CH3) 13C NMR (125 MHz CDCl3) δ 1565 1391 1292 1234 1207 352 155

2-Ethylaminopyrimidine (4n) [13]


Pale yellow solid 99 mg 40 yield 1H NMR (500 MHz CDCl3) δ 821 (2H d J = 48 Hz ArH) 644 (1H

t J = 48 Hz ArH) 572 (1H br NH) 342-336 (2H m NCH2) 119

(3H t J = 71 Hz CH3) 13C NMR (125 MHz CDCl3) δ 1624 1580 1102 362 149

Reference

[1] T Tokuyasu S Kunikawa A Masuyama M Nojima Org Lett 2002 4 3595-3598

[2] A Ricci G Seconi M Taddei Org Synth 1997 74 84-90

[3] T K Hyster T Rovis J Am Chem Soc 2010 132 10565-10569

[4] Y Jo J Ju J Choe K H Song S Lee J Org Chem 2009 74 6358-6361

[5] L Ackermann A V Lygin N Hofmann Angew Chem Int Ed 2011 50 6379-6382

[6] K Seth M Nautiyal P Purohit N Parikh A K Chakraborti Chem Commun 2015

51 191-194

[7] B L Tran B Li M Driess J F Hartwig J Am Chem Soc 2014 136 2555-2563

[8] Y-F Guo T-L Ren B-H Xu Y-F Wang S-J Zhang Asian J Org Chem 2016

5 568-574

[9] X Wang R A Widenhoefer Organometallics 2004 23 1649-1651

[10] S Hanada E Tsutsumi Y Motoyama H Nagashima J Am Chem Soc 2009 131

15032-15040

[11] E Artuso I Degani R Fochi C Magistris Synthesis 2008 10 1612-1618

[12] M Zhang S Imm S Bahn L Neubert H Neumann M Beller Angew Chem Int

Ed 2012 51 3905-3909

[13] Y Watanabe Y Morisaki T Kondo T Mitsudo J Org Chem 1996 61 4214-4218

S10

1H NMR spectrum of 1a (CDCl3 500 MHz)

13C NMR spectrum of 1a (CDCl3 125 MHz)

S11

29Si NMR spectrum of 1a (CDCl3 100 MHz)

1H NMR spectrum of 1b (CDCl3 500 MHz)

S12

13C NMR spectrum of 1b (CDCl3 125 MHz)

29Si NMR spectrum of 1b (CDCl3 100 MHz)

S13

1H NMR spectrum of 1c (CDCl3 500 MHz)

13C NMR spectrum of 1c (CDCl3 125 MHz)

S14

29Si NMR spectrum of 1c (CDCl3 100 MHz)

1H NMR spectrum of 1d (CDCl3 500 MHz)

S15

13C NMR spectrum of 1d (CDCl3 125 MHz)

29Si NMR spectrum of 1d (CDCl3 100 MHz)

S16

1H NMR spectrum of 1e (CDCl3 500 MHz)

13C NMR spectrum of 1e (CDCl3 125 MHz)

S17

29Si NMR spectrum of 1e (CDCl3 100 MHz)

1H NMR spectrum of 1f (CDCl3 500 MHz)

S18

13C NMR spectrum of 1f (CDCl3 125 MHz)

29Si NMR spectrum of 1f (CDCl3 100 MHz)

S19



S20



S21



S22



S23



S24



S25



S26



S27



S28



S29



S30

1H NMR spectrum of 4g (CDCl3 500 MHz)

13C NMR spectrum of 4g (CDCl3 125 MHz)

S31

1H NMR spectrum of 4h (CDCl3 500 MHz)

13C NMR spectrum of 4h (CDCl3 125 MHz)

S32

1H NMR spectrum of 4i (CDCl3 500 MHz)

13C NMR spectrum of 4i (CDCl3 125 MHz)

S33

1H NMR spectrum of 4j (CDCl3 500 MHz)

13C NMR spectrum of 4j (CDCl3 125 MHz)

S34

1H NMR spectrum of 4k (CDCl3 500 MHz)

13C NMR spectrum of 4k (CDCl3 125 MHz)

S35

1H NMR spectrum of 4l (CDCl3 500 MHz)

13C NMR spectrum of 4l (CDCl3 125 MHz)

S36

1H NMR spectrum of 4n (CDCl3 500 MHz)

13C NMR spectrum of 4n (CDCl3 125 MHz)

S2

Optimization of Reaction Conditions of N-Ethylation of Benzamide 2a with 1a

Table S1 The effect of the amount of peroxide [a]

[a] Reaction conditions bezamide 2a (01 mmol 10 eq) 1a (X eq) CuI (10

mol) L1 (10 mol) benzene (025 mL 04 M) 100 degC 24 h [b] Yield was

determined by 1H NMR spectroscopy using DMF as an internal standard [c]

1a (02 mmol 20 eq) was added to the reaction mixture after stirring for 1h

Table S2 The effect of the amount of catalyst and ligand [a]


20 eq) CuI (X mol) bipyrimidine (X mol) benzene (025 mL 04

M) 100 degC 24 h [b] Yield was determined by 1H NMR spectroscopy

using DMF as an internal standard

Entry X 3a () [b] 2a () [b]

1 10 37 56

2 20 60 23

3 30 66 24

4 [c] 20+20 81 4

Entry X Yield of 3a () [b]

1 5 55

2 10 60

3 20 62

S3







1 none 45

2 L1 60

3 L2 71

4 L3 61

5 L4 71

6 L5 57

7 L6 50

8 L7 53

9 L8 39

10 L9 0

11 L10 44

12 L11 38

S4












401 29Si NMR (100 MHz CDCl3) δ 2862



13C NMR (125







1195 1081 884 782 cm1






778 cm1

S5



123-112 (10H m CH2) 085-080 (2H m CH2) 012 (12H




(neat) 2918 2848 1446 1247 818 778 cm1






725 cm1














1676 1349 1315 1287 1270 351 150

S6












316 201 137





δ 1668 1352 1314 1287 1269 420 230




(1H m NCH) 206-202 (2H m CH2) 177-174 (2H m CH2)


MHz CDCl3) δ 1668 1353 1314 1287 1270 488 334 257 251





1377 1333 1289 1284 352 150

S7





1338 1319 1286 1261 352 150




716 (2H d J = 88 Hz ArH) 600 (1H br NH) 353-347




3305 2921 1749 1634 1540 1255 1198 cm1





(125 MHz CDCl3) δ 1671 1622 1287 1273 1139 555 350 152



723 (2H d J = 82 Hz ArH) 603 (1H br NH) 352-347 (2H






NMR (125 MHz CDCl3) δ 1702 1369 1361 1311 1299 1267 1258 348 198

151

S8




CDCl3) δ 1573 1453(m) 1433-1432 (m) 1413 (m) 1389-



1655 1502 1326 1265 991 735 cm1





1584 1483 1437 1138 1121 341 150



751-749 (2H m ArH) 737-734 (3H m ArH) 637 (1H d J

= 156 Hz CH) 555 (1H br NH) 347-341 (2H m NCH2)




977 cm1








1286 1285 1263 387 344 319 149





1367 1285-1280(3 peaks overlap) 665 359 152

S9










Reference







51 191-194



5 568-574



15032-15040



Ed 2012 51 3905-3909


S10



S11



S12



S13



S14



S15



S16



S17



S18



S19



S20



S21



S22



S23



S24



S25



S26



S27



S28



S29



S30



S31



S32



S33



S34



S35



S36



S3







1 none 45

2 L1 60

3 L2 71

4 L3 61

5 L4 71

6 L5 57

7 L6 50

8 L7 53

9 L8 39

10 L9 0

11 L10 44

12 L11 38

S4












401 29Si NMR (100 MHz CDCl3) δ 2862



13C NMR (125







1195 1081 884 782 cm1






778 cm1

S5



123-112 (10H m CH2) 085-080 (2H m CH2) 012 (12H




(neat) 2918 2848 1446 1247 818 778 cm1






725 cm1














1676 1349 1315 1287 1270 351 150

S6












316 201 137





δ 1668 1352 1314 1287 1269 420 230




(1H m NCH) 206-202 (2H m CH2) 177-174 (2H m CH2)


MHz CDCl3) δ 1668 1353 1314 1287 1270 488 334 257 251





1377 1333 1289 1284 352 150

S7





1338 1319 1286 1261 352 150




716 (2H d J = 88 Hz ArH) 600 (1H br NH) 353-347




3305 2921 1749 1634 1540 1255 1198 cm1





(125 MHz CDCl3) δ 1671 1622 1287 1273 1139 555 350 152



723 (2H d J = 82 Hz ArH) 603 (1H br NH) 352-347 (2H






NMR (125 MHz CDCl3) δ 1702 1369 1361 1311 1299 1267 1258 348 198

151

S8




CDCl3) δ 1573 1453(m) 1433-1432 (m) 1413 (m) 1389-



1655 1502 1326 1265 991 735 cm1





1584 1483 1437 1138 1121 341 150



751-749 (2H m ArH) 737-734 (3H m ArH) 637 (1H d J

= 156 Hz CH) 555 (1H br NH) 347-341 (2H m NCH2)




977 cm1








1286 1285 1263 387 344 319 149





1367 1285-1280(3 peaks overlap) 665 359 152

S9










Reference







51 191-194



5 568-574



15032-15040



Ed 2012 51 3905-3909


S10



S11



S12



S13



S14



S15



S16



S17



S18



S19



S20



S21



S22



S23



S24



S25



S26



S27



S28



S29



S30



S31



S32



S33



S34



S35



S36



S4












401 29Si NMR (100 MHz CDCl3) δ 2862



13C NMR (125







1195 1081 884 782 cm1






778 cm1

S5



123-112 (10H m CH2) 085-080 (2H m CH2) 012 (12H




(neat) 2918 2848 1446 1247 818 778 cm1






725 cm1














1676 1349 1315 1287 1270 351 150

S6












316 201 137





δ 1668 1352 1314 1287 1269 420 230




(1H m NCH) 206-202 (2H m CH2) 177-174 (2H m CH2)


MHz CDCl3) δ 1668 1353 1314 1287 1270 488 334 257 251





1377 1333 1289 1284 352 150

S7





1338 1319 1286 1261 352 150




716 (2H d J = 88 Hz ArH) 600 (1H br NH) 353-347




3305 2921 1749 1634 1540 1255 1198 cm1





(125 MHz CDCl3) δ 1671 1622 1287 1273 1139 555 350 152



723 (2H d J = 82 Hz ArH) 603 (1H br NH) 352-347 (2H






NMR (125 MHz CDCl3) δ 1702 1369 1361 1311 1299 1267 1258 348 198

151

S8




CDCl3) δ 1573 1453(m) 1433-1432 (m) 1413 (m) 1389-



1655 1502 1326 1265 991 735 cm1





1584 1483 1437 1138 1121 341 150



751-749 (2H m ArH) 737-734 (3H m ArH) 637 (1H d J

= 156 Hz CH) 555 (1H br NH) 347-341 (2H m NCH2)




977 cm1








1286 1285 1263 387 344 319 149





1367 1285-1280(3 peaks overlap) 665 359 152

S9










Reference







51 191-194



5 568-574



15032-15040



Ed 2012 51 3905-3909


S10



S11



S12



S13



S14



S15



S16



S17



S18



S19



S20



S21



S22



S23



S24



S25



S26



S27



S28



S29



S30



S31



S32



S33



S34



S35



S36



S5



123-112 (10H m CH2) 085-080 (2H m CH2) 012 (12H




(neat) 2918 2848 1446 1247 818 778 cm1






725 cm1














1676 1349 1315 1287 1270 351 150

S6












316 201 137





δ 1668 1352 1314 1287 1269 420 230




(1H m NCH) 206-202 (2H m CH2) 177-174 (2H m CH2)


MHz CDCl3) δ 1668 1353 1314 1287 1270 488 334 257 251





1377 1333 1289 1284 352 150

S7





1338 1319 1286 1261 352 150




716 (2H d J = 88 Hz ArH) 600 (1H br NH) 353-347




3305 2921 1749 1634 1540 1255 1198 cm1





(125 MHz CDCl3) δ 1671 1622 1287 1273 1139 555 350 152



723 (2H d J = 82 Hz ArH) 603 (1H br NH) 352-347 (2H






NMR (125 MHz CDCl3) δ 1702 1369 1361 1311 1299 1267 1258 348 198

151

S8




CDCl3) δ 1573 1453(m) 1433-1432 (m) 1413 (m) 1389-



1655 1502 1326 1265 991 735 cm1





1584 1483 1437 1138 1121 341 150



751-749 (2H m ArH) 737-734 (3H m ArH) 637 (1H d J

= 156 Hz CH) 555 (1H br NH) 347-341 (2H m NCH2)




977 cm1








1286 1285 1263 387 344 319 149





1367 1285-1280(3 peaks overlap) 665 359 152

S9










Reference







51 191-194



5 568-574



15032-15040



Ed 2012 51 3905-3909


S10



S11



S12



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316 201 137





δ 1668 1352 1314 1287 1269 420 230




(1H m NCH) 206-202 (2H m CH2) 177-174 (2H m CH2)


MHz CDCl3) δ 1668 1353 1314 1287 1270 488 334 257 251





1377 1333 1289 1284 352 150

S7





1338 1319 1286 1261 352 150




716 (2H d J = 88 Hz ArH) 600 (1H br NH) 353-347




3305 2921 1749 1634 1540 1255 1198 cm1





(125 MHz CDCl3) δ 1671 1622 1287 1273 1139 555 350 152



723 (2H d J = 82 Hz ArH) 603 (1H br NH) 352-347 (2H






NMR (125 MHz CDCl3) δ 1702 1369 1361 1311 1299 1267 1258 348 198

151

S8




CDCl3) δ 1573 1453(m) 1433-1432 (m) 1413 (m) 1389-



1655 1502 1326 1265 991 735 cm1





1584 1483 1437 1138 1121 341 150



751-749 (2H m ArH) 737-734 (3H m ArH) 637 (1H d J

= 156 Hz CH) 555 (1H br NH) 347-341 (2H m NCH2)




977 cm1








1286 1285 1263 387 344 319 149





1367 1285-1280(3 peaks overlap) 665 359 152

S9










Reference







51 191-194



5 568-574



15032-15040



Ed 2012 51 3905-3909


S10



S11



S12



S13



S14



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S7





1338 1319 1286 1261 352 150




716 (2H d J = 88 Hz ArH) 600 (1H br NH) 353-347




3305 2921 1749 1634 1540 1255 1198 cm1





(125 MHz CDCl3) δ 1671 1622 1287 1273 1139 555 350 152



723 (2H d J = 82 Hz ArH) 603 (1H br NH) 352-347 (2H






NMR (125 MHz CDCl3) δ 1702 1369 1361 1311 1299 1267 1258 348 198

151

S8




CDCl3) δ 1573 1453(m) 1433-1432 (m) 1413 (m) 1389-



1655 1502 1326 1265 991 735 cm1





1584 1483 1437 1138 1121 341 150



751-749 (2H m ArH) 737-734 (3H m ArH) 637 (1H d J

= 156 Hz CH) 555 (1H br NH) 347-341 (2H m NCH2)




977 cm1








1286 1285 1263 387 344 319 149





1367 1285-1280(3 peaks overlap) 665 359 152

S9










Reference







51 191-194



5 568-574



15032-15040



Ed 2012 51 3905-3909


S10



S11



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CDCl3) δ 1573 1453(m) 1433-1432 (m) 1413 (m) 1389-



1655 1502 1326 1265 991 735 cm1





1584 1483 1437 1138 1121 341 150



751-749 (2H m ArH) 737-734 (3H m ArH) 637 (1H d J

= 156 Hz CH) 555 (1H br NH) 347-341 (2H m NCH2)




977 cm1








1286 1285 1263 387 344 319 149





1367 1285-1280(3 peaks overlap) 665 359 152

S9










Reference







51 191-194



5 568-574



15032-15040



Ed 2012 51 3905-3909


S10



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Reference







51 191-194



5 568-574



15032-15040



Ed 2012 51 3905-3909


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Supporting Information · S2 Optimization of Reaction Conditions of N-Ethylation of Benzamide 2a...

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Transcript of Supporting Information · S2 Optimization of Reaction Conditions of N-Ethylation of Benzamide 2a...