Supporting Information

Aqueous Single Step Synthesis and Structural Characterization of Allylated, Propargylated, and Benzylated 3-Substituted 3-Aminooxindoles

Sameer A. Karpe, Man Singh*, and L. Raju Chowhan

School of Chemical Sciences, Central University of Gujarat, Gandhinagar, Gujarat - 382030,

India

Tel. No. 079-23260210, Fax No. 079-23260076E-mail address: skarpe.karpe@gmail.com, mansingh50@hotmail.com, and

rajuchowhan@gmail.com

1. General Information ………………………………………….………………..S2

2. Spectral Characterization Data……………………………………………..….S4

3. FTIR, NMR and Mass Spectral Data for compounds (1.5a-1.5o) …………….S15

S1

1. General information:

Isatin, 5-chloroisatin, alkyl halides, and ammonium chloride used were of analytical

grade obtained from Sigma-Aldrich and used without further purification. Isatin imine

derivatives were synthesized by following the method reported in literature[1] and

characterized with standard spectroscopic techniques to confirm the structures. All organic

solvents used were obtained from SD Fine Chemicals Ltd. (Mumbai, India). The Milli-Q-

water (Millipore SAS 67/20 Mosheim) of 10−7 S cm−1 was used for preparing an aqueous

saturated NH4Cl solution. Zinc dust of 90% purity was used. Reaction progress was

monitored by TLC (Merck, silica GF257) using ethyl acetate and n-hexane (4:6 v/v) as a

mobile phase and spots were visualized under UV light (RICO scientific industries, Model

RSUV-5). FTIR spectra were recorded on a Perkin-Elmer Spectrum FTIR spectrometer using

KBr plates, and characteristic wavenumbers are given in cm⁻1. Mass spectral analysis was

achieved on Agilent Technologies G6520B LCMS (QTOF) mass spectrometry with +ESI

ionization method. The 0.02% trifluoroacetic acid in water and pure acetonitrile was used as a

mobile phase in a ratio of 30:70% v/v, on an Agilent Zorbax 300 SB-C18 column (3.5 mm,

4.6 × 50 mm) with a flow rate of 0.5 mL min-1. The 1H and 13C NMR spectra were recorded at

room temperature (rt) in 5 mm tube using Bruker Avance III-500 MHz spectrometer in

deuterated chloroform (CDCl3) and deuterated dimethyl sulphoxide (DMSO-d6) with TMS as

an internal standard. The chemical shifts are given in δ ppm and coupling constant (J) in Hz.

Splitting patterns are described by singlet (s), doublet (d), triplet (t), quartet (q), quintet (q),

sextet (s), and multiplet (m).

1.1. General procedure for Synthesis of Isatin imines and its Derivatives

Aromatic amine (2.0 mmol) and isatin (2.0 mmol) were taken in a round bottom flask

containing 08 mL absolute ethanol. In this solution, a catalytic amount of glacial acetic acid

S2

was added at room temperature. The reaction mixture was refluxed for 3 to 5 hours. The

completion of the reaction was confirmed by TLC. Then the reaction mixture was allowed to

cool to room temperature. The solid product was filtered on a Buchner funnel. The crude

product was recrystallized from methanol.[1]

1.2. General procedure for Allylation, benzylation and propargylation of

Isatin imine and its Derivative

To a stirred solution of isatin imine (1.0 mmol) in THF (10 mL), saturated aqueous

NH4Cl (10 mL) and corresponding bromide 1.4a-h (2.0 mmol) were added successively. To

the resulting solution, Zn powder (2.0 mmol) was added portion wise at room temperature.

This mixture was stirred for 15 min. Then, the reaction mixture was transferred to the

separatory funnel. Two liquid layers were separated, and the aqueous layer was extracted

with 1:1 solution of EtOAc: THF (4 × 15 mL). Combined organic layers were washed with

brine (30 mL) and dried over anhydrous Na2SO4. After concentrating under vacuum, the

residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate = 9/1 to

7/3). The final product was washed with 1:1 solution of diethyl ether: n-hexane (2 × 5 mL) to

yield pure solid. This procedure was followed for the synthesis of compounds 1.5a-1.5o.

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2. Spectral Characterization Data (1.5a-1.5o):

1.5a3-allyl-3-(4-bromophenylamino)indolin-2-one (1.5a): Yield: 63%; whitish brown

solid; IR (KBr) 3362 (secondary amine N-H stretch), 3239 (secondary amide N-H stretch),

3176-3083 (aromatic ring sp2 C-H stretch), 2978-2929 (alkane C-H stretch), 1724 (amide

C=O stretch), 1593 (amide N-H bend) cm-1; 1H NMR (500 MHz, DMSO-d6) δ 10.71 (s, 1H,

Ar-NHCO-), 7.24 (td, J = 6.31 and 1.26 Hz, 1H, Ar-H), 7.14 (d, J = 7.25 Hz, 1H, Ar-H),

7.09-7.05 (m, 2H, Ar-H), 6.97 (td, J = 6.94 and 0.95 Hz, 1H, Ar-H), 6.90 (d, J = 7.88 Hz, 1H

Ar-H), 6.56 (s, 1H, Ar-NH), 6.16-6.13 (m, 2H, Ar-H), 5.47-5.38 (m, 1H, C=C-H), 5.00-4.96

(m, 2H, C=CH2), 2.71-2.67 (m, 1H, C=C-CH2), 2.54-2.51 (m, 1H, C=C-CH2); 13C NMR (125

MHz, CDCl3-DMSO-d6) δ 176.54, 143.94, 139.44, 129.37, 128.97, 127.77, 127.02, 121.79,

120.09, 118.02, 113.59, 108.36, 106.23, 62.18, 41.98; LCMS m/z: calcd. for C17H15BrN2O:

342.04, found 343.0461 [M+H]+, 365.0281 [M+Na]+, 381.0025 [M+K]+.

1.5b3-(4-bromophenylamino)-3-(prop-2-ynyl)indolin-2-one (1.5b): Yield: 56%;

whitish brown solid; IR (KBr) 3346 (secondary amine N-H stretch), 3288 (terminal alkynes

≡C-H stretch), 3151 (secondary amide N-H stretch), 3090-3014 (aromatic ring sp2 C-H

stretch), 2963-2807 (alkane C-H stretch), 2124 (terminal alkynes C≡C stretch), 1720 (amide

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C=O stretch), 1595 (amide N-H bend) cm-1; 1H NMR (500 MHz, DMSO-d6) δ 10.83 (s, 1H,

Ar-NHCO-), 7.29-7.23 (m, 2H, Ar-H), 7.10-7.06 (m, 2H, Ar-H), 7.00-6.96 (m, 1H, Ar-H),

6.93 (d, J = 7.57 Hz, 1H), 6.65 (s, 1H, Ar-NH), 6.22-6.14 (m, 2H, Ar-H), 2.88 (dd, 2J = 13.24

and 4J = 2.52 Hz, 1H, C≡C-CH), 2.84 (t, J = 2.52 Hz, 1H, -C≡C-H), 2.71 (dd, 2J = 13.56 and

4J = 2.52 Hz, 1H, C≡C-CH); 13C NMR (125 MHz, CDCl3-DMSO-d6) δ 175.56, 143.54,

139.76, 129.26, 127.26, 126.99, 121.82, 120.03, 113.57, 108.22, 106.40, 91.80, 76.08, 60.94,

27.52; LCMS m/z: calcd. for C17H13BrN2O: 340.02, found 341.0307 [M+H]+, 343.0289

[M+2+H]+.

1.5c3-benzyl-3-(4-bromophenylamino)indolin-2-one (1.5c): Yield: 50%; white solid;

IR (KBr) 3375 (secondary amine N-H stretch), 3168 (secondary amide N-H stretch), 3088-

3028 (aromatic ring sp2 C-H stretch), 2947-2917 (alkane C-H stretch), 1716 (amide C=O

stretch), 1591 (amide N-H bend) cm-1; 1H NMR (500 MHz, CDCl3-DMSO-d6) δ 10.25 (s,

1H, Ar-NHCO-), 8.15 (s, 1H, Ar-NH), 7.14-7.05 (m, 2H, Ar-H), 7.06-6.98 (m, 4H, Ar-H),

6.95-6.93 (m, 1H, Ar-H), 6.79-6.75 (m, 2H, Ar-H), 6.62-6.59 (m, 1H, Ar-H), 6.55 (s, 1H, Ar-

H), 6.19 (d, J = 8.20 Hz, 2H, Ar-H), 3.25-3.17 (dd, J = 11.98 Hz, 2H, Ar-CH2-C); 13C NMR

(125 MHz, CDCl3-DMSO-d6) δ 176.37, 144.03, 139.73, 132.11, 129.46, 128.57, 127.36,

127.14, 125.67, 125.02, 122.21, 120.04, 113.95, 108.20, 106.50, 63.98, 43.75; LCMS m/z:

calcd. for C21H17BrN2O: 392.05, found 393.0615 [M+H]+, 395.0598 [M+2+H]+.

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1.5d3-(4-bromophenylamino)-3-(cyclohex-2-enyl)indolin-2-one (1.5d): Yield: 70%;

pale yellow solid; IR (KBr) 3337 (secondary amine N-H stretch), 3160 (secondary amide N-

H stretch), 3094-3033 (aromatic ring sp2 C-H stretch), 2937-2860 (alkane C-H stretch), 1708

(amide C=O stretch), 1598 (amide N-H bend) cm-1; 1H NMR (500 MHz, DMSO-d6) δ 10.73

(s, 1H, Ar-NHCO-), 7.25 (td, J = 6.62 and 0.95 Hz, 1H, Ar-H), 7.07-7.02 (m, 3H, Ar-H),

6.94-6.89 (m, 2H, Ar-H), 6.54 (s, 1H, Ar-NH), 6.20-6.15 (m, 2H, Ar-H), 6.02-5.98 (m, 1H, -

C-CH=CH-C), 5.86-5.82 (m, 1H, -C-CH=CH-C), 2.74 (br s, 1H, C=C-CH), 1.91-1.83 (m,

1H, C=C-CH), 1.72-1.60 (m, 2H, -CH2-), 1.56-1.50 (m, 1H, -CH2-), 1.40-1.31 (m, 1H, -

CH2-), 0.80-0.72 (m, 1H, -CH2-); 13C NMR (125 MHz, CDCl3-DMSO-d6) δ 176.80, 144.52,

140.24, 129.34, 128.43, 127.12, 126.44, 124.15, 123.04, 119.84, 113.99, 108.11, 106.37,

65.14, 42.03, 23.00, 21.06, 19.58; LCMS m/z: calcd. for C20H19BrN2O: 382.07, found

383.0779 [M+H]+, 385.0761 [M+2+H]+.

1.5e3-(4-bromophenylamino)-3-(2-methylbut-3-en-2-yl)indolin-2-one (1.5e): Yield:

80%; white solid; IR (KBr) 3313 (secondary amine N-H stretch), 3178 (secondary amide N-

H stretch), 3090 (aromatic ring sp2 C-H stretch), 2967-2810 (alkane C-H stretch), 1716

(amide C=O stretch), 1593 (amide N-H bend) cm-1; 1H NMR (500 MHz, DMSO-d6) δ 10.52

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(br s, 1H, Ar-NHCO-), 8.08 (br s, 1H, Ar-NH), 7.24-7.19 (m, 1H, Ar-H), 7.08 (d, J = 8.20

Hz, 1H, Ar-H), 7.00-6.86 (m, 3H, Ar-H), 6.26-6.12 (m, 3H, Ar-H), 5.22-5.11 (m, 3H, -

CH=CH2), 1.15 (s, 3H, -CH3), 1.09 (s, 3H, -CH3); 13C NMR (125 MHz, CDCl3-DMSO-d6) δ

176.24, 143.77, 140.74, 140.00, 129.32, 127.23, 126.23, 123.87, 119.40, 113.91, 113.16,

108.06, 106.56, 66.87, 41.47, 19.96, 18.59; LCMS m/z: calcd. for C19H19BrN2O: 370.07,

found 371.0780 [M+H]+.

1.5f3-(4-bromophenylamino)-3-(but-3-en-2-yl)indolin-2-one (1.5f): Yield: 60%; pale

yellow solid; IR (KBr) 3379 (secondary amine N-H stretch), 3167 (secondary amide N-H

stretch), 3089 (aromatic ring sp2 C-H stretch), 2995-2875 (alkane C-H stretch), 1721 (amide

C=O stretch), 1594 (amide N-H bend) cm-1; 1H NMR (500 MHz, DMSO-d6) δ 10.62 (br s,

1H, Ar-NHCO-), 8.20 (br s, 1H, Ar-NH), 7.15 (s, 1H, Ar-H), 7.05-6.85 (m, 4H, Ar-H), 6.16

(s, 2H, Ar-H), 6.09-5.88 (m, 1H, Ar-H), 5.43-5.32 (m, 1H, -C-CH=CH2), 5.22-5.12 (m, 1H,

C-CH=CH2), 5.08-4.94 (m, 1H, C-CH=CH2), 2.74 (br s, 1H, -CH-CH=CH2), 1.19 (br s, 3H, -

CH3); 13C NMR (125 MHz, CDCl3-DMSO-d6) δ 176.48, 143.99, 140.01, 135.32, 129.31,

127.17, 126.24, 122.60, 119.83, 115.50, 113.81, 108.24, 106.29, 64.98, 44.15, 12.48; LCMS

m/z: calcd. for C18H17BrN2O: 356.05, found 357.0612 [M+H]+, 359.0594 [M+2+H]+.

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1.5gmethyl 4-(3-(4-bromophenylamino)-2-oxoindolin-3-yl)but-2-enoate (1.5g): Yield:

30%; pale yellow solid; IR (KBr) 3463 (secondary amine N-H stretch), 3374 (secondary

amide N-H stretch), 3226-3032 (aromatic ring sp2 C-H stretch), 2959-2853 (alkane C-H

stretch), 1708 (amide C=O stretch), 1620 (C=C conjugated to ester carbonyl), 1594 (amide

N-H bend) cm-1; 1H NMR (500 MHz, DMSO-d6) δ 10.77 (s, 1H, Ar-NHCO-), 7.94 (br s, 1H,

Ar-NH), 7.29-7.21 (m, 2H, Ar-H), 7.07 (d, J = 7.88 Hz, 1H, Ar-H), 6.96 (t, J = 7.88 Hz, 1H,

Ar-H), 6.88 (d, J = 6.62 Hz, 1H, Ar-H), 6.24-6.15 (m, 2H, Ar-H), 6.03 (m, 1H, Ar-H ), 5.79-

5.68 (m, 1H, -CO-CH=CH-), 5.24 (m, 1H, -CO-CH=CH-), 3.73 (br s, 3H, -COOCH3), 3.58

(d, J = 11.66 Hz, 2H, -CH=CH-CH2); 13C NMR (125 MHz, DMSO-d6) δ 192.48, 179.80,

176.18, 169.92, 141.71, 131.23, 129.80, 125.27, 121.79, 121.69, 116.36, 111.72, 110.12,

109.43, 64.95, 51.93, 30.72; LCMS m/z: calcd. for C19H17BrN2O3: 400.04, found 401.0523

[M+H]+, 403.0509 [M+2+H]+.

1.5h3-(4-bromophenylamino)-3-(1-phenylethyl)indolin-2-one (1.5h): Yield: 77%;

whitish brown solid; IR (KBr) 3333 (secondary amine N-H stretch), 3292 (secondary amide

S8

N-H stretch), 3152-3029 (aromatic ring sp2 C-H stretch), 2966-2818 (alkane C-H stretch),

1716 (amide C=O stretch), 1596 (amide N-H bend) cm-1; 1H NMR (500 MHz, CDCl3-

DMSO-d6) δ 10.06 (s, 1H, Ar-NHCO-), 8.23 (s, 1H, Ar-NH), 7.33 (d, J = 6.62 Hz, 1H, Ar-

H), 7.25 (t, J = 7.88 Hz, 1H, Ar-H), 7.13 (br s, 2H, Ar-H), 7.02 (m, 3H, Ar-H), 6.84 (t, J =

7.25 Hz, 1H, Ar-H), 6.73 (d, J = 8.51 Hz, 1H, Ar-H), 6.62 (t, J = 8.20 Hz, 2H, Ar-H), 6.19

(br s, 2H, Ar-H), 3.85 (br s, 1H, Ar-CH-C), 1.53 (d, J = 7.57 Hz, 3H, -CH3); 13C NMR (125

MHz, CDCl3-DMSO-d6) δ 176.68, 144.43, 140.38, 140.27, 138.01, 137.89, 129.33, 127.64,

127.15, 126.80, 126.10, 125.61, 125.59, 125.20, 114.30, 114.02, 108.27, 108.02, 106.36,

66.53, 65.65, 45.50, 44.84, 13.66, 12.61; LCMS m/z: calcd. for C22H19BrN2O: 406.07, found

407.0781 [M+H]+, 409.0763 [M+2+H]+.

1.5i3-allyl-3-(phenylamino)indolin-2-one (1.5i): Yield: 73%; whitish brown solid; IR

(KBr) 3314 (secondary amine N-H stretch), 3137 (secondary amide N-H stretch), 3082-3031

(aromatic ring sp2 C-H stretch), 2887-2825 (alkane C-H stretch), 1711 (amide C=O stretch),

1604 (amide N-H bend) cm-1; 1H NMR (500 MHz, DMSO-d6) δ 10.62 (br s, 1H, Ar-

NHCO-), 7.22 (t, J = 7.57 Hz, 1H, Ar-H), 7.13 (d, J = 7.25 Hz, 1H, Ar-H), 6.94 (t, J = 7.57

Hz, 1H, Ar-H), 6.89 (d, J = 2.52 Hz, 3H, Ar-H), 6.46 (t, J = 7.88 Hz, 1H, Ar-H), 6.24 (s, 1H,

Ar-NH), 6.19 (d, J = 7.57 Hz, 2H, Ar-H), 5.49-5.39 (m, 1H, -C=C-H), 5.00-4.95 (m, 2H, -

C=CH2 ), 2.72-2.65 (m, 1H, C=C-CH2), 2.54 (m, 1H, C=C-CH2); 13C NMR (125 MHz,

DMSO-d6) δ 178.53, 146.41, 141.14, 130.90, 130.05, 128.71, 128.60, 123.56, 121.82, 119.75,

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116.74, 113.24, 109.92, 63.80, 43.67; LCMS m/z: calcd. for C17H16N2O: 264.13, found

265.1356 [M+H]+, 287.1182 [M+Na]+, 303.0920 [M+K]+.

1.5j3-(phenylamino)-3-(prop-2-ynyl)indolin-2-one (1.5j): Yield: 70%; brown solid; IR

(KBr) 3344 (secondary amine N-H stretch), 3284 (terminal alkynes ≡C-H stretch), 3140

(secondary amide N-H stretch), 3086-3022 (aromatic ring sp2 C-H stretch), 2893-2815

(alkane C-H stretch), 2125 (terminal alkynes C≡C stretch), 1715 (amide C=O stretch), 1603

(amide N-H bend) cm-1; 1H NMR (500 MHz, CDCl3-DMSO-d6) δ 10.69 (s, 1H, Ar-NHCO-),

8.17 (s, 1H, Ar-NH), 7.30- 7.20 (m, 1H, Ar-H), 6.98-6.86 (m, 4H, Ar-H), 6.50 (t, J = 7.57

Hz, 1H, Ar-H), 6.24 (d, J = 7.88 Hz, 2H, Ar-H), 6.19 (s, 1H, Ar-H), 2.88 (d, J = 13.87 Hz,

1H, -C≡C-CH), 2.71 (d, J = 13.87 Hz, 1H, -C≡C-CH), 2.57 (s, 1H, -C≡C-H); 13C NMR (125

MHz, CDCl3-DMSO-d6) δ 176.26, 144.45, 140.00, 127.79, 127.28, 126.92, 122.02, 120.15,

115.58, 111.99, 108.35, 76.43, 71.49, 61.17, 27.94; LCMS m/z: calcd. for C17H14N2O:

262.11, found 263.1199 [M+H]+, 285.1023 [M+Na]+, 301.0760 [M+K]+.

1.5k

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3-benzyl-3-(phenylamino)indolin-2-one (1.5k): Yield: 61%; whitish brown solid;

IR (KBr) 3340 (secondary amine N-H stretch), 3136 (secondary amide N-H stretch), 3061-

3028 (aromatic ring sp2 C-H stretch), 2938-2823 (alkane C-H stretch), 1709 (amide C=O

stretch), 1603 (amide N-H bend) cm-1; 1H NMR (500 MHz, DMSO-d6) δ 10.32 (s, 1H, Ar-

NHCO-), 7.19 (d, J = 7.25 Hz, 1H, Ar-H), 7.17-7.09 (m, 2H, one proton of Ar-H and one

proton of Ar-NH), 7.06 (t, J = 7.25 Hz, 2H, Ar-H), 6.96 (t, J = 7.57 Hz, 1H, Ar-H), 6.91 (t, J

= 6.94 Hz, 2H, Ar-H), 6.77 (d, J = 6.94 Hz, 2H, Ar-H), 6.60 (d, J = 7.25 Hz, 1H, Ar-H), 6.48

(s, 2H, Ar-H), 6.24 (d, J = 8.20 Hz, 2H, Ar-H), 3.25 (d, J = 12.61 Hz, 1H, Ph-CH2-), 3.18 (d,

J = 12.61 Hz, 1H, Ph-CH2-); 13C NMR (125 MHz, DMSO-d6) δ 178.24, 146.47, 141.32,

133.91, 130.12, 129.51, 128.74, 128.59, 127.35, 126.68, 123.88, 121.59, 116.75, 113.44,

109.58, 65.47, 45.19; LCMS m/z: calcd. for C21H18N2O: 314.14, found 315.1520 [M+H]+,

337.1340 [M+Na]+, 353.1078 [M+K]+.

1.5l3-allyl-5-chloro-3-(phenylamino)indolin-2-one (1.5l): Yield: 60%; white solid; IR

(KBr) 3373 (secondary amine N-H stretch), 3254 (secondary amide N-H stretch), 3106-3014

(aromatic ring sp2 C-H stretch), 2943-2846 (alkane C-H stretch), 1731 (amide C=O stretch),

1603 (amide N-H bend) cm-1; 1H NMR (500 MHz, DMSO-d6) δ 10.69 (br s, 1H, Ar-

NHCO-), 8.14 (br s, 1H, Ar-NH), 7.21 (s, 1H, Ar-H), 7.12 (s, 1H, Ar-H), 6.91 (br s, 3H, Ar-

H), 6.52 (br s, 1H, Ar-H), 6.22 (d, J = 6.62 Hz, 2H, Ar-H), 5.59-5.47 (m, 1H, H2C=C-H),

5.03 (d, 3J = 12.61 Hz, 2H, H2C=C-H), 2.71 (br s, 1H, -C=C-CH2), 2.11 (s, 1H, -C=C-CH2);

13C NMR (125 MHz, CDCl3-DMSO-d6) δ 176.82, 144.46, 138.43, 130.70, 128.86, 127.11,

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126.91, 124.85, 122.01, 118.49, 115.72, 111.94, 109.78, 62.56, 42.21; LCMS m/z: calcd. for

C17H15ClN2O: 298.09, found 299.0969 [M+H]+.

1.5m5-chloro-3-(phenylamino)-3-(prop-2-ynyl)indolin-2-one (1.5m): Yield: 55%; pale

yellow solid; IR (KBr) 3377 (secondary amine N-H stretch), 3277 (terminal alkynes ≡C-H

stretch), 3138 (secondary amide N-H stretch), 3107 (aromatic ring sp2 C-H stretch), 2902-

2840 (alkane C-H stretch), 2121 (terminal alkynes C≡C stretch), 1731 (amide C=O stretch),

1604 (amide N-H bend) cm-1; 1H NMR (500 MHz, CDCl3-DMSO-d6) δ 10.87 (s, 1H, Ar-

NHCO-), 8.23 (s, 1H, Ar-NH), 7.28 (m, 1H, Ar-H), 6.93 (d, J = 7.25 Hz, 3H, Ar-H), 6.53 (t,

J = 7.57 Hz, 1H, Ar-H), 6.34 (br s, 1H, Ar-H), 6.23 (d, J = 7.57 Hz, 2H, Ar-H), 2.93 (d, J =

14.82 Hz, 1H, C≡C-CH), 2.70 (m, 2H, one proton of C≡C-CH, one proton of -C≡C-H); 13C

NMR (125 MHz, CDCl3-DMSO-d6) δ 175.74, 144.13, 138.88, 129.88, 127.19, 126.97,

124.46, 121.98, 115.68, 111.75, 109.63, 76.03, 71.88, 61.32, 27.55; LCMS m/z: calcd. for

C17H13ClN2O: 296.07, found 297.0810 [M+H]+.

1.5n

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3-benzyl-5-chloro-3-(phenylamino)indolin-2-one (1.5n): Yield: 27%; brown solid;

IR (KBr) 3345 (secondary amine N-H stretch), 3100 (secondary amide N-H stretch), 3024

(aromatic ring sp2 C-H stretch), 2889-2843 (alkane C-H stretch), 1708 (amide C=O stretch),

1601 (amide N-H bend) cm-1; 1H NMR (500 MHz, DMSO-d6) δ 10.49 (br s, 1H, Ar-

NHCO-), 7.22-7.17 (m, J = 7.25 Hz, 2H, Ar-H), 7.16-7.08 (m, 3H, Ar-H), 6.94 (t, J = 7.88

Hz, 2H, Ar-H), 6.82 (d, J = 6.31 Hz, 2H, Ar-H), 6.62 (d, J = 7.88 Hz, 1H, Ar-H), 6.55 (s,

1H, Ar-NH), 6.53-6.50 (m, 1H, Ar-H), 6.23 (d, J = 7.88 Hz, 2H, Ar-H), 3.31 (d, J = 12 Hz,

1H, Ph-CH2), 3.18 (d, J = 11.98 Hz, 1H, Ph-CH2); 13C NMR (125 MHz, DMSO-d6) δ 178.02,

146.22, 140.25, 133.63, 131.85, 130.13, 128.76, 128.66, 127.51, 126.88, 125.78, 123.98,

117.08, 113.39, 111.05, 65.74, 44.92; LCMS m/z: calcd. for C21H17ClN2O: 348.10, found

349.1128 [M+H]+, 371.0948 [M+Na]+.

1.5o3-allyl-3-(4-bromophenylamino)-5-chloroindolin-2-one (1.5o): Yield: 45%; white

solid; IR (KBr) 3379 (secondary amine N-H stretch), 3245 (secondary amide N-H stretch),

3078-3009 (aromatic ring sp2 C-H stretch), 2976-2855 (alkane C-H stretch), 1736 (amide

C=O stretch), 1596 (amide N-H bend) cm-1; 1H NMR (500 MHz, DMSO-d6) δ 10.72 (br s,

1H, Ar-NHCO-), 7.21 (s, 1H, Ar-H), 7.11 (s, 1H, Ar-H), 7.02 (s, 2H, Ar-H), 6.89 (s, 1H, Ar-

H), 6.36 (br s, 1H, Ar-NH), 6.17 (t, J = 3.47 Hz, 2H, Ar-H), 5.57-5.46 (m, 1H, H2C=CH-

CH2-), 5.08-4.99 (m, 2H, H2C=CH-CH2-), 2.71 (br s, 1H, H2C=CH-CH2-), 2.58 (br s, 1H,

H2C=CH-CH2-); 13C NMR (125 MHz, CDCl3-DMSO-d6) δ 176.54, 143.76, 138.43, 130.14,

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129.74, 128.71, 127.15, 125.10, 122.10, 118.69, 113.83, 109.95, 107.02, 62.66, 42.16;

LCMS m/z: calcd. for C17H14BrClN2O: 376.00, found 377.0069 [M+H]+.

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Product 1.5a

Figure S1. FTIR spectra of 1.5a

Figure S2. 1H NMR spectra of 1.5a

S15

Figure S3. 13C NMR spectra of 1.5a

Figure S4. Mass spectra of 1.5a

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M+K

M+Na

M+H1.5a

Product 1.5b

Figure S5. FTIR spectra of 1.5b

Figure S6. 1H NMR spectra of 1.5b

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Figure S7. 13C NMR spectra of 1.5b

Figure S8. Mass spectra of 1.5b

S18

M+H

1.5b

Product 1.5c

Figure S9. FTIR spectra of 1.5c

Figure S10. 1H NMR spectra of 1.5c

S19

Figure S11. 13C NMR spectra of 1.5c

Figure S12. Mass spectra of 1.5c

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1.5c

M+H

Product 1.5d

Figure S13. FTIR spectra of 1.5d

Figure S14. 1H NMR spectra of 1.5d

S21

Figure S15. 13C NMR spectra of 1.5d

Figure S16. Mass spectra of 1.5d

S22

M+H

1.5d

Product 1.5e

Figure S17. FTIR spectra of 1.5e

Figure S18. 1H NMR spectra of 1.5e

S23

Figure S19. 13C NMR spectra of 1.5e

Figure S20. Mass spectra of 1.5e

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M+H 1.5e

Product 1.5f

Figure S21. FTIR spectra of 1.5f

Figure S22. 1H NMR spectra of 1.5f

S25

Figure S23. 13C NMR spectra of 1.5f

Figure S24. Mass spectra of 1.5f

S26

M+H

1.5f

Product 1.5g

Figure S25. FTIR spectra of 1.5g

Figure S26. 1H NMR spectra of 1.5g

S27

Figure S27. 13C NMR spectra of 1.5g

Figure S28. Mass spectra of 1.5g

S28

M+H

1.5g

Product 1.5h

Figure S29. FTIR spectra of 1.5h

Figure S30. 1H NMR spectra of 1.5h

S29

Figure S31. 13C NMR spectra of 2.5h

Figure S32. Mass spectra of 1.5h

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M+H

1.5h

Product 1.5i

Figure S33. FTIR spectra of 1.5i

Figure S34. 1H NMR spectra of 1.5i

S31

Figure S35. 13C NMR spectra of 1.5i

Figure S36. Mass spectra of 1.5i

S32

1.5i

M+K

M+Na

M+H

Product 1.5j

Figure S37. FTIR spectra of 1.5j

Figure S38. 1H NMR spectra of 1.5j

S33

Figure S39. 13C NMR spectra of 1.5j

Figure S40. Mass spectra of 1.5j

S34

M+K

M+Na

M+H

1.5j

Product 1.5k

Figure S41. FTIR spectra of 1.5k

Figure S42. 1H NMR spectra of 1.5k

S35

Figure S43. 13C NMR spectra of 1.5k

Figure S44. Mass spectra of 1.5k

S36

M+K

M+Na

M+H

1.5k

Product 1.5l

Figure S45. FTIR spectra of 1.5l

Figure S46. 1H NMR spectra of 1.5l

S37

Figure S47. 13C NMR spectra of 1.5l

Figure S48. Mass spectra of 1.5l

S38

M+1

1.5l

Product 1.5m

Figure S49. FTIR spectra of 1.5m

Figure S50. 1H NMR spectra of 1.5m

S39

Figure S51. 13C NMR spectra of 1.5m

Figure S52. Mass spectra of 1.5m

S40

M+H

1.5m

Product 1.5n

Figure S53. FTIR spectra of 1.5n

Figure S54. 1H NMR spectra of 1.5n

S41

Figure S55. 13C NMR spectra of 1.5n

Figure S56. Mass spectra of 1.5n

S42

M+Na

2.5n

M+H

Product 1.5o

Figure S57. FTIR spectra of 1.5o

Figure S58. 1H NMR spectra of 1.5o

S43

Figure S59. 13C NMR spectra of 1.5o

Figure S60. Mass spectra of 1.5o

S44

M+H

1.5o

References

[1] Verma, M.; Pandeya, S. N.; Singh, K. N.; Stables, J. P. Acta Pharm. 2004, 54, 49-56.

S45