convenient approach in the synthetic method

1

Supporting Information

Chlorotrifluoroethylidenes: An efficient and convenient approach in the synthetic method

Abhay Atmaram Uparea,b, Pradip K. Gadekarb, Kiran Jadhavb, H. Sivaramakrishnanb and Selvaraj Mohana Roopana,*aChemistry of Heterocycles and Natural Product Research Lab, Department of Chemistry, School of Advanced Science, Vellore Institute of Technology, Vellore – 632014, Tamil Nadu, India. [email protected] of Process Development, Piramal Enterprises Ltd., Lighthall A Wing, Hiranandani Business Park, Sakivihar Road, Chandivali, Andheri (East), Mumbai 400072, India.

Supplementary Information

General. All laboratory reagents and solvents were purchased from either Aldrich or lab

grade chemical Indian supplier’s (viz. Spectrochem), unless otherwise specified. We used

mCPBA: 3-chloroperoxybenzoic acid, DCM: dichloromethane, EtOAc: ethyl acetate, CsCO3:

Caesium carbonate, LDA: Lithium diisopropylamide, NaHMDS: Sodium

Bis(trimethylsilyl)amide, DBU: 1,8-Diazabicyclo[5.4.0]undec-7-ene, DMF:

Dimethylformamide, H2O2: Hydrogen peroxide, THF: Tetrahydrofuran, OXONE®:

Potassium peroxymonosulfate without further purification. 2- bromo-2-chloro-1,1,1-

trifluoroethane that is Halothane were obtained from Piramal critical care, India and used

without further purification.

All reactions carried out under a nitrogen atmosphere using dry glassware. Reactions were

monitor by thin-layer chromatography (TLC) using Merck pre-coated silica gel 60 F254

plates, with visualization under UV light. Reactions were purified using a Combi-Flash

Sq16x system or by chromatography column performed with the indicated solvents using

silica gel 60 (particle size 0.040-0.063 mm). Purity and yields refer to chromatographically

and spectroscopically pure compounds.

1H, 13C, 19F NMR spectra were recorded on a Varian Mercury Plus 300 MHz NMR (Bruker)

spectrometer. 1H chemical shifts (δ) were determined relative to internal tetramethylsilane

(TMS) at 0.00 and reported in ppm. 13C chemical shifts (δ) were determined relative to 13C

signal of the solvent DMSO (39.52 ppm) and CFCl3 as reference for 19F chemical shift. 19F

recorded by decoupling of protons. J values reported in Hertz. Mass-spectral (MS) data

recorded on GC/MS system Mass TQ8040-Agilent couple with GC 2010 plus Shimadzu.

Electronic Supplementary Material (ESI) for RSC Advances.This journal is © The Royal Society of Chemistry 2020

2

Melting points recorded using a Veego (VMP) D capillary melting point apparatus (Veego

Instruments Corp. Mumbai, India) and were uncorrected.

Analytical method Details.

GCMS method Details

GC-MS analysis were performed on GC 2010 plus Shimadzu Gas Chromatograph equipped

with DB624 30 m x 0.32 ID x 1.8 µm columns and or ZB5 30 m x 0.25 ID x 0.25 µm phase

thickness, aligned with Agilent TQ8040 MSD mass spectrometer operating under ionisation

by electron impact (EI) at 70 eV.

Conditions: Helium flow was maintained at 1 mL/min. The ion source temperature was

maintained at 250, MS quad temperature at 150°C, the interface temperature at 250°C, and the

inlet temperature at 250°C and Solvent Cut Time was set for 1.00 min.

GC conditions:

Column Oven Temperature was set at 40°C with Injection Temperature 250 °C with split

mode (Split Ratio 1:50).

The flow control mode was set at linear Velocity with pressure 49.5 kPa and Column Flow

set at 1.00 mL/min

Oven Temperature Program was set @ 40°C with 15 min hold, @ 15°C to 240°C (25 min

hold)

GC Purity method Details:

GC purity analysis were performed on GC 7890A Agilent Gas Chromatograph equipped with

Rtx 624 30 m x 0.32 ID x 3.0 µm columns

GC conditions:

Column Oven Temperature was set at 40°C with Injection Temperature 250°C with split

mode (Split Ratio 1: 20.0).

Column Flow set at 1.00 mL/min

Oven Temperature Program was set @ 40°C with 15 min hold, @ 15°C to 240°C with 30 min

hold.

3

Experimental procedure and spectroscopic data of compounds

S

NS

CF3Cl

Preparation of 2- [(1-chloro-2,2,2-trifluoroethyl)sulfanyl]-1,3-benzothiazole (10):

2- bromo-2-chloro-1,1,1- trifluoroethane (Halothane) (167.0 g, 847.7 mmol) was

added dropwise to a stirred suspension of 1,3-benzothiazole-2-thiol 9 (50.0g, 299

mmol), sodium bicarbonate (50.0 g, 595 mmol) and 85% sodium dithionite (104.0 g,

597 mmol) in 200.0 ml of DMF at 25 to 30 °C within 30 minutes. The reaction

mixture was heated and stirred for 5-6 h at 55 °C. The reaction mass was poured into

200 ml water and extracted with 3 X 100 ml ethyl acetate. Combined organic layer

was washed with water followed by brine and dried over anhydrous sodium sulphate.

The solvent was removed under vacuum and further purified by column

chromatography to yield 2-[(1-chloro-2,2,2-trifluoroethyl)sulfanyl]-1,3 benzothiazole

58.3 g.

Yield: 69%; Pale yellow liquid; 1H NMR (300 MHz, CDCl3): 8.12 - 8.09 (d, J = 9Hz,

1H), 8.04 - 8.01 (d, J = 9Hz, 1H), 7.57 - 7.54 (t, 1H), 7.52 - 7.43 (t, 1H), 7.26 - 7.19 (q,

J = 6Hz, 15Hz, 1H) meets with reported compound; 19F NMR(282.4 MHz, DMSO-

d6): -71.42 (s, CF3, -3F) (reported -73.09 at 188 MHz in CDCl3)22; GC-MS (ESI 70 eV

+ve) m/z 284 (M+1), 283, 248, 228, 184, 166, 135, 122, 108, 69, 50; GC % purity

99.52%.

S

NS

CF3

ClO

O

Procedure for preparation of 2-[(1-chloro-2,2,2-trifluoroethyl)sulfonyl]- 1,3 benzothiazole

(Sulfone )(11):

H2O2 50 wt % solution (220 g. 3.23 mol) was added dropwise to a stirred solution of 2-

[(1-chloro-2,2,2-trifluoroethyl)sulfanyl]-1,3 benzothiazole 10 (51.0 g 179.76 mmol) in

acetic acid (160.0 2.67 mmol) over a period of 8 hrs. at 60°C. The completion of

reaction is monitored by TLC. The reaction mass was concentrated to 1 volume under

vacuum. The pH of the reaction mass adjusted to 8 to 7 using saturated sodium

bicarbonate solution and product was extracted with ethyl acetate. The organic layer

4

was washed with water followed by brine and dried over anhydrous sodium sulphate.

The solvent removed under vacuum and purified by column chromatography to yield

2-[(1-chloro-2,2,2-trifluoroethyl)sulfonyl]-1,3-benzothiazole 32 g.

Yield: 56%; White solid; m.p 100-102°C; 1H NMR (300 MHz, DMSO-d6): 8.47 - 8.42

(m, 1H), 8.41 - 8.34 (m, 1H), 7.84 - 7.80 (m, 1H), 7.79 - 7.74 (m, 1H), 7.62 - 7.55 (q, J

= 6Hz, 15Hz, 1H); 13C NMR (75 MHz, DMSO-d6): 161.5 (Ar C, benzthiazole C,

N=C-S, -1C), 152.4 (Ar C ring junction attached to nitrogen, -1C), 137.9 (Ar C ring

junction attached to sulphur, -1C), 129.6, 129.0, 125.9, 124.2 (Ar C, -4C), 126.9,

123.2, 119.4, 115.7 (q, JCF = 280.5Hz, CF3, -1C), 69.4, 69.0, 68.5, 68.1 (q, JCF =

33.0Hz, aliphatic C, Cl-C-CF3, -1C); 19F NMR(282.4 MHz, DMSO-d6): -66.05 (s,

CF3, -3F); GC-MS (ESI 70 eV +ve) m/z 284 (M+1), 315, 198, 170, 134, 117, 90, 69,

50; HRMS (ESI +ve) m/z [M+H]+ calcd for C9H6ClF3NO2S2: 315.9471, found

315.9475, m/z [M+Na]+ C9H5ClF3NNaO2S2: 337.9292, found 337.9294; GC % purity

94.1%.

Procedure for preparation of olefin:

O2NCl

F3C

H

Preparation of (E/Z)-1-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-4-nitrobenzene (12a):

DBU (2 ml, 13.37 mmol) diluted in 5 ml THF was added to a stirred solution of

sulfone 11 (2.0g, 6.34 mmol) and 4-nitrobenzaldehyde 12 (0. 957g, 6.33 mmol) in 15

ml of THF at -50 to -60 °C slowly in 20 minutes. After addition the mixture was

stirred for 1 h at -50 to -60 °C temperature. The reaction was then allowed to warm up

to room temperature and stirred for a further 1hr. The completion of the reaction was

monitored by TLC. The reaction mass was quenched with water. The aqueous layer

was extracted with ethyl acetate 3 x 30 ml. The combined organic layer dried over

sodium sulphate, filtered and evaporated under reduced pressure. The product was

purified by column chromatography (silica, pet ether/AcOEt 95:5) to yield (E)-1-(2-

chloro-3,3,3-trifluoroprop-1-en-1-yl)-4-nitrobenzene 12a. 1.28 g.

Mixture E / Z 12a: Yield 80 %; Yellow oil; 19F NMR (282.4 MHz, DMSO- d6): -

61.05 (s, CF3, -3F, E- isomer), -67.70 (s, CF3, -3F, Z- isomer); GC-MS (ESI 70 eV

5

+ve) m/z 252(M+1), 251, 221, 185, 169, 143,120, 101, 75, 50 (similar fragments for

both isomers- E/Z= 83.40 : 16.60); GC Purity: 84.65%, RT – 33.85 min, E-isomer +

11.46% RT -33.92 min, Z- isomer.

Pure E isomer of 12a: yellow oil; 1H NMR (300 MHz, DMSO-d6): δ 8.29 - 8.28 (d, J

= 3 HZ, 2H), 7.92 (s, 1H), 7.62 - 7.59 (d, J = 9Hz, 2H); 13C NMR (75 MHz, DMSO-

d6): 147.9 (Ar C attached to NO2, -1C), 139.3(Ar C attached to olefinic bond -C=C, -

1C), 137.5(3)- 137.5 (Olefinc C attached to Ar ring -C=C, -1C), 130.1(4), 130.1(1) (Ar

C meta to NO2, -2C), 124.1, 123.9 (Ar C ortho to NO2, -2C), 125.9, 122.2, 118.6,

115.0 (q, JCF = 272.25Hz, CF3, -1C) 122.0, 121.5, 121.0,120.5 (q, JCF = 37.5Hz,

olefinic C, =C-CF3Cl, -1C); GC-MS (ESI 70 eV +ve) m/z 252(M+1), 251, 221, 185,

169, 143,120, 101, 75, 50; GC Purity: 99.65% (RT – 33.85 min, E-isomer).

Compounds 13a to 25a were synthesised using procedure as described for

compound 12a.

O2N Cl

CF3

H

(E/Z)-1-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-3-nitrobenzene (13a):

1.25 g; Yield: 78%; Yellow oil; 1H NMR (300 MHz, DMSO-d6): δ 8.28-8.21 (m, 2H),

7.82 (s, 1H), 7.80-7.71 (m, 2H); 13C NMR (75 MHz, DMSO-d6): 147.9 (Ar C attached

to NO2, -1C), 137.2(9) - 137.2(6) (Ar C attached to olefinic bond -C=C, -1C), 135.2(9)

- 135.2(6) (Ar C, para to NO2, -1C), 134.2(Ar C, meta to NO2, -1C), 130.5 (Ar C, ortho

to NO2, -1C), 124.3 (Ar C, ortho to NO2 -1C), 123.5, 123.4(Olefinc C attached to Ar

ring -C=C, -1C), 125.9, 122.3, 118.7, 115.0 (q, JCF = 272.25Hz, CF3, -1C) 121.8,

121.3, 120.8(1), 120.3(1) (q, JCF = 37.5Hz, olefinic C, =C-CF3Cl, -1C); Note: other

carbons are of minor isomer; 19F NMR(282.4 MHz, DMSO-d6): -61.01 (s, CF3, -3F,

E- isomer), -67.70 (s, CF3, -3F, Z- isomer); GC-MS (ESI 70 eV +ve) m/z 252 (M+1),

251, 207, 185, 169, 151, 120, 101, 75, 50 (similar fragments for minor isomer –E:Z =

70 : 30); GC Purity: 98.96%, RT – 33.59 min, E-isomer + minor, Z- isomer not

separated.

6

NC

Cl

CF3

H

(E/Z)-4-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)benzonitrile (14a):

1.21 g; Yield: 82%; Colourless oil; 1H NMR (300 MHz, DMSO-d6): δ 7.96 (s, 1H),

7.91-7.85 (t, J = 9Hz, 2H), 7.53 - 7.50 (d, J = 9Hz, 2H); 13C NMR (75 MHz, DMSO-

d6): 137.8 (Olefinc C attached to Ar ring -C=C, -1C), 137.4 (Ar C attached to olefinic

bond -C=C, -1C), 132.7, (Ar C, -2C), 129.6(3) - 129.6(1) (Ar C, -2C), 125.9, 122.2,

118.6, 115.0 (q, JCF = 272.25Hz, CF3, -1C), 121.7, 121.2, 120.7, 120.2 (q, JCF =

37.5Hz, olefinic C, =C-CF3Cl, -1C); 118.8 (CN, -1C), 112.1 (Ar C attached to CN, -

1C), Note: other carbons are of minor isomer; 19F NMR(282.4 MHz, DMSO-d6): -


+ve) m/z 231 (M+1), 231, 212, 196, 176, 149, 127, 100, 75, 50 (similar fragments for

minor isomer – E:Z = 68 : 32); GC Purity (E+Z): 72.39%, RT – 32.49 min, E-isomer

+ 24.69% RT - 32.61 min, Z- isomer. (Manuscript Reference number 13).

Cl

CF3

H

(E/Z)-1-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-4-isopropylbenzene (15a):

0.93 g; Yield: 59%; Colourless liquid; 1H NMR (300 MHz, DMSO-d6): δ 7.76-7.25

(m, 5H), 2.88-2.87 (s, 1H), 1.18 (s, 6H); 19F NMR(282.4 MHz, DMSO-d6): -60.55 (s,

CF3, -3F, E- isomer), -67.05 (s, CF3, -3F, Z- isomer); GC-MS (ESI 70 eV +ve) m/z

250(M+1), 233, 213, 197, 177, 151, 128, 99, 77, 51(similar fragments for minor

isomer – E:Z = 78 : 22); GC Purity (E+Z): 71.70%, RT – 29.92 min, E-isomer +

23.64% RT - 30.25 min, Z- isomer.

O

F Cl

CF3

H

(E/Z)-4-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2-fluoro-1-methoxybenzene (16a):

7


(m, 4H), 3.89-3.86(t, J = 9Hz, OMe -3H); 13C NMR (75 MHz, DMSO-d6): 152.9,

152.8, 149.6(7), 149.6(0) (dd, Ar C attached to F, -1C), 148.5, 148.4 (Ar C attached to

OMe, -1C), 137.8 (olefinic C attached to Ar ring, –C=C, -1C) 128.3, 128.2 (Ar C

attached to olefinc C, -C=C, -1C), 126.1(7), 126.1(4) (Ar C meta to OMe, -1C),

124.9, 124.8 (Ar C ortho to OMe, -1C), 123.1 – 116.6 (CF3, & olefinic C, =C-CF3Cl

not well resolved due to mixture of Z & E isomers -2C), 113.9(2). 113.9(1) (Ar C

ortho to F, -1C), 56.5, 56.4 (s, OMe - 1C), Note: other carbons are of minor isomer; 19F NMR(282.4 MHz, DMSO-d6): -60.61 (s, CF3, -3F, E- isomer), -67.07 (s, CF3, -

3F, Z- isomer), -134.55, 135.40 (Ar –F); GC-MS (ESI 70 eV +ve) m/z 255(M+1),

254, 239, 211, 191, 161, 156, 125, 107, 81, 57(similar fragments for minor isomer –

E:Z = 73 : 27); GC Purity (E+Z): 68.96%, RT – 30.25 min, E-isomer + 26.51% RT -

30.56 min, Z- isomer.

SCF3

Cl

(E/Z)-(4-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)phenyl)(methyl)sulfane (17a):


(d, J = 6Hz, 1H), 7.32-7.28 (s, 4H); 13C NMR (75 MHz, DMSO-d6): 141.0 (Ar C

attached to S-methyl, -1C), 138.8 (Ar C attached to olefinic bond -C=C, -1C), 130.9

(Olefinc C attached to Ar ring -C=C, -1C), 129.5(3), 129.5(0) (Ar C, -2C), 125.5 (Ar

C, -2C), 126.2, 122.6, 119.0, 115.4 (q, JCF = 272.25Hz, CF3, -1C), 118.8, 118.3,

117.8, 117.3 (q, JCF = 37.5Hz, olefinic C, =C-CF3Cl, -1C), 14.5 (C, CH3 attached to

S, -1C), Note: other carbons are of minor isomer; 19F NMR(282.4 MHz, DMSO-d6): -


+ve) m/z 254 (M+1), 252, 219, 202, 169, 151, 133, 89, 69, 50 (similar fragments for

minor isomers – E:Z = 80 : 20); GC Purity (E+Z): 72.43%, RT - 33.23 min, E-isomer

+ 20.44% RT - 33.74 min, Z- isomer.

F

Br

Cl

CF3

H

8

(E/Z)-1-bromo-2-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-4-fluorobenzene (18a).

1.62 g; Yield 84%; Colourless liquid; 1H NMR (300 MHz, DMSO-d6): δ 7.77 - 7.71

(m, 1H), 7.64 (s, 1H), 7.32 – 7.22 (m, 2H); 13C NMR (75 MHz, DMSO-d6): 162.6,

162.5, 159.4, 159.3 (dd, Ar C attached to F, -1C), 136.4 (olefinic C attached to Ar

ring, –C=C, -1C) 135.2, 135.1 (Ar C attached to olefinc C, -C=C, -1C), 134.1, 133.9

(Ar C meta to F, -1C), 125.3, 121.7, 118.1, 114.4 (q, JCF = 272.25Hz, CF3, -1C)

122.4, 121.9, 121.4,120.9 (q, JCF = 36.75Hz, olefinic C, =C-CF3Cl, -1C), 118.1(6),

118.1(1), 117.8, 117.6 (dd, Ar C ortho to F, -1C), 117.2(6), 117.2(3), 116.9(4).

116.9(0) (dd, Ar C ortho to F, -1C), 116.2 (Ar C attached to Br, -1C), and minor

isomer; 19F NMR(282.4 MHz, DMSO-d6): -62.52 (s, CF3, -3F, E- isomer, major), -

67.95 (s, CF3, -3F, Z- isomer), -113.68, -114.5 (Ar C attached to F -1C); GC-MS (ESI

70 eV +ve) m/z 305 (M+1), 304, 301, 267, 249, 223, 188, 169, 157, 119, 99, 69, 50;

GC Purity: 95.56%, RT – 29.26 (E & Z isomers not resolved in current method).

Cl

Cl Cl

CF3

H

(E/Z)-1,2-dichloro-4-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)benzene (19a).


(m, 3H), 7.31.- 7.0 (d, J = 3Hz, 1H); 13C NMR (75 MHz, DMSO-d6): 136.7(6),

136.7(3) (olefinic C attached to Ar ring, –C=C, -1C), 133.1 (s, Ar C attached to

olefinc C, -C=C, -1C), 132.4 (s, Ar C attached to Cl, -1C), 131.6 (s, Ar C attached to

Cl, -1C), 130.9 (s, Ar C ortho to Cl, -1C), 130.6(2), 130.6(0) (d, Ar C ortho to Cl, -

1C), 128.9(4), 128.9(1) (d, Ar C meta to Cl, -1C), 125.9, 122.2, 118.6, 115.0 (q, JCF =

272.25Hz, CF3, -1C) 121.4, 120.9, 120.4, 119.9 (q, JCF = 37.5Hz, olefinic C, =C-

CF3Cl, -1C), and minor isomer aromatic carbon 133.4, 132.2, 132.0,131.9, 131.2,

130.4(9), 130.4(3), 130.3, 130.1, 129.3, -6C); 19F NMR(282.4 MHz, DMSO-d6): -


+ve) m/z 278(M+2), 274; 239, 219, 204,169, 135, 119, 99, 74, 69, 50 (similar

fragments for minor isomer – E:Z = 79 : 21); GC Purity (E+Z): 74.82%, RT – 31.68

min, E-isomer + 22.04% RT - 31.84 min, Z- isomer.

9

S

Br

ClF3C

H

(E/Z)-3-bromo-2-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)benzo[b]thiophene (20a –A &

20a - B):

20a - A:


sulfone 11 (2.0g, 6.34 mmol) and 3-bromobenzo[b]thiophene-2-carbaldehyde 20

(1530.0 mg, 6.35 mmol) in 15 ml of THF at -50 to -60°C slowly in 20 minutes. After

addition the mixture was stirred for 1 h at -50 to -60°C temperature. The reaction was

then allowed to warm up to room temperature and stirred for another 1 h. The

completion of the reaction was monitored by TLC. The reaction mass was quenched

with water. The aqueous layer was extracted with ethyl acetate 3 x 30 ml. The

combined organic layer dried over sodium sulphate, filtered and evaporated under

reduced pressure. The product was purified by column chromatography (silica, pet

ether/AcOEt 95:5) to yield (E/Z)-3-bromo-2-(2-chloro-3,3,3-trifluoroprop-1-en-1-

yl)benzo[b]thiophene 20a-A.

1.99 g; Yield: 92%; Yellow Solid; mp 49-51°C ; 1H NMR (300 MHz, DMSO-d6): δ

8.10 - 8.07 (m, 1H), 7.84 - 7.74 (m, 2H), 7.60 - 7.51 (m, 2H); 19F NMR(282.4 MHz,

DMSO-d6): -61.98 (s, CF3, -3F, E- isomer), -67.13 (s, CF3, -3F, Z- isomer); GC-MS

(ESI 70 eV +ve) m/z 342 (M+1), 307, 281, 261, 241, 226, 192, 176, 157, 113, 88, 69,

50 (similar fragments for minor isomer – E:Z = 32 : 68); GC Purity (E+Z): 21.78%,

RT – 42.72 min, E-isomer + 77.28% RT - 44.61 min, Z- isomer.

20a –B: Reaction performed at higher temperature compared to compounds 20a - A


sulfone 11 (2.0g, 6.34 mmol) and 3-bromobenzo[b]thiophene-2-carbaldehyde 20

(1530.0 mg, 6.35 mmol) in 15 ml of THF at -20 to -10°C slowly in 20 minutes. After

addition the mixture was stirred for 1 h at -20 to -10°C temperature. The reaction was

then allowed to warm up to room temperature and stirred for another 1 h. The

completion of the reaction was monitored by TLC. The reaction mass was quenched

10

with water. The aqueous layer was extracted with ethyl acetate 3 x 30 ml. The

combined organic layer dried over sodium sulphate, filtered and evaporated under

reduced pressure. The product was purified by column chromatography (silica, pet

ether/AcOEt 95:5) to yield (E/Z)-3-bromo-2-(2-chloro-3,3,3-trifluoroprop-1-en-1-

yl)benzo[b]thiophene 20a-B.

1.95 g; Yield: 90 %; Yellow Solid; 1H NMR (300 MHz, DMSO-d6): δ 8.09 - 8.06 (m,

1H), 7.83 - 7.74 (m, 2H), 7.58 - 7.52 (m, 2H); 19F NMR(282.4 MHz, DMSO-d6): -


+ve) m/z 342 (M+1), 307, 281, 261, 241, 226, 192, 176, 157, 113, 88, 69, 50 (similar

fragments for both isomers – E/Z = 67 : 33); GC Purity (E+Z): 75.98%, RT – 42.53

min, E-isomer + 19.28% RT - 44.39 min, Z- isomer.

S CF3

ClH

(E/Z)-2-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)thiophene (21a):

0.72 g; Yield: 53%; Colourless liquid; 1H NMR (300 MHz, DMSO-d6): δ 7.84 - 7. 80

(m, 2H), 7.42 - 7.41 (m, 1H), 7.16 - 7.13(m, 1H); 13C NMR (75 MHz, DMSO-d6):

136.1 (olefinic C attached to thiophene ring, –C=C, -1C), 134.3, 134.2 (d, thiophene

ring 2nd position C attached to olefinc C, -C=C, -1C), 132.1(5), 132.1(3) (d, thiophene

ring 5th position C, -1C), 131.3(8), 131.3(5) (d, thiophene ring 3rd position C, -1C),

128.1 (s, thiophene ring 4th position C, -1C), 126.3, 122.7, 119.1, 115.5 (q, JCF =

270.75Hz, CF3, -1C) 115.7, 115.2, 114.7, 114.2 (q, JCF = 39.75Hz, olefinic C, =C-

CF3Cl, -1C), and minor isomer aromatic carbon 134.1(9), 133.1(6), 132.7, 127.8,( -

4C); GC-MS (ESI 70 eV +ve) m/z 213(M+1), 212, 193, 177, 157, 115, 108, 69, 58

(similar fragments for both isomers – E:Z = 82 : 18); GC Purity (E+Z): 74.41%, RT –

27.67 min, E-isomer + 21.67% RT - 27.87 min, Z- isomer.

F3CCl

H

(E/Z)-2-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)naphthalene (22a):

11

1.39 g; Yield: 85%; Colourless liquid; 1H NMR (300 MHz, DMSO-d6): δ 7.99 -

7.88(m, 5H), 7.59 - 7.54 (m, 2H), 7.54 - 7.41(d, J = 9Hz, 1H); 13C NMR (75 MHz,

DMSO-d6): 139.3(5),139.3(2) (olefinic C attached to Ar ring, –C=C, -1C), 133.1,

132.7, 130.1, 128.6, 128.5, 128.4, 128.0, 127.6, 127.2, 125.9 (Aromatic carbon -10C),

126.2, 122.6, 118.9, 115.3 (q, JCF = 272.25Hz, CF3, -1C) 119.9, 119.4, 118.9, 115.3

(q, JCF = 39.75Hz, olefinic C, =C-CF3Cl, -1C), and minor isomer aromatic carbon

133.8, 132.8, 132.6, 132.5, 131.2, 129.0(8), 129.0(5), 128.2, 127.3, 126.7 aromatic

acrbon, -10C); 19F NMR(282.4 MHz, DMSO-d6): -60.58 (s, CF3, -3F, E- isomer), -

67.14 (s, CF3, -3F, Z- isomer); GC-MS (ESI 70 eV +ve) m/z 257(M+1), 256, 237,

221, 201, 170, 152, 126, 100, 75, 69, 51(similar fragments for both isomers – E:Z =

83 : 17); GC Purity (E+Z): 75.29%, RT – 35.90 min, E-isomer + 20.43% RT - 36.45

min, Z- isomer.

CF3

ClH

(E/Z)-3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-1,1'-biphenyl (23a):

1.62 g; Yield 90.%; 1H NMR (300 MHz, DMSO-d6): δ 7.84- 7.63(m, 1H), 7.61-7.44

(m,4H), 7.40-7.31(m,5H); 19F NMR(282.4 MHz, DMSO-d6): -60.56 (s, CF3, -3F, E-

isomer), -67.23 (s, CF3, -3F, Z- isomer); GC-MS (ESI 70 eV +ve) m/z 283(M+1), 282

base peak, 269, 246, 227, 183, 178, 152, 113, 88, 76, 51 (similar fragments for both

isomers – E:Z = 84 : 16); GC Purity (E+Z): 78.23%, RT – 40.20 min, E-isomer +

17.88% RT - 40.70 min, Z- isomer.

H

Cl

CF3

(E/Z)-(4-chloro-5,5,5-trifluoropent-3-en-1-yl)benzene (24a):

1.19 g; Yield: 80 %; Colourless liquid; 19F NMR (282.4 MHz, DMSO-d6): -61.51 (s,

CF3, 3F, E- isomer), -67.67 (s, 3F, Z- isomer); GC-MS (ESI 70 eV +ve) m/z

234(M+1), 199, 177, 143, 128, 91 base peak, 65, 51 (similar fragments for both

isomers – E:Z = 32 : 68); GC Purity (E+Z): 28.39%, RT – 29.17 min, E-isomer +

71.61% RT - 29.42 min, Z- isomer).

12

H

Cl

CF3

(E/Z)-4-chloro-5,5,5-trifluoropenta-1,3-dien-1-yl)benzene (25a):

1.18 g; Yield: 78 %; 19F NMR (282.4 MHz, DMSO-d6): -60.60, 60.69 (s, CF3, 3F, E-

isomer), -66.75 (s, 3F, Z- isomer); GC-MS (ESI 70 eV +ve) m/z 232(M+1), 232,197,

177, 146, 128, 102, 69, 51 (similar fragments for both isomers – E:Z = not separated);

GC Purity (E+Z): 93.78%, RT – 30.98 min, E & Z- isomer not separated in current

method).

13

S2.1: Figure 1 - 1H NMR spectrum of compound 10

SN

S

Cl

F3C

14

S2.1: Figure 2 - 19F NMR spectrum of compound 10

SN

S

Cl

F3C

15

S2.1: Figure 3 - GC Mass spectrum of compound 10

S

NS

ClF3C

16

S2.1: Figure 4 - GC Purity of compound 10

S

NS

ClF3C

17

S2.2: Figure 1 - 1H NMR spectrum of compound 11

SN

S

CF3Cl

O O

18

S2.2: Figure 2 - 13C NMR spectrum of compound 11

SN

S

CF3Cl

O O

19

S2.2: Figure 3 - 19F NMR spectrum of compound 11

SN

S

CF3Cl

O O

20

S2.2: Figure 4 - GC Mass spectrum of compound 11

S

NS

CF3

ClO

O

21

S2.2: Figure 5 - HRMS spectrum of compound 11

S

NS

CF3

ClO

O

22

S2.2: Figure 6 - GC Purity of compound 11

S

NS

CF3

ClO

O

23

S2.3: Figure 1 - 19F NMR spectrum of compound 12a (Mixture)

ClF3C

O2N

24

S2.3: Figure 2 - GC MS spectrum of compound 12a (Mixture)

Cl

CF3O2N

25

S2.3: Figure 3 - GC Purity of compound 12a (Mixture)

Cl

CF3O2N

26

S2.3: Figure 4 - 1H NMR spectrum of compound 12a (Pure)

ClF3C

O2N

27

S2.3: Figure 5 - 13C NMR spectrum of compound 12a (Pure)

ClF3C

O2N

28

S2.3: Figure 6 - GC Mass spectrum of compound 12a (Pure)

Cl

CF3O2N

29

S2.3: Figure 7 - GC Purity of compound 12a (Pure)

Cl

CF3O2N

30

S2.4: Figure 1 - 1H NMR spectrum of compound 13a

ClF3C

NO2

31

S2.4: Figure 2 - 13C NMR spectrum of compound 13a

ClF3C

NO2

32

S2.4: Figure 3 - 19F NMR spectrum of compound 13a

ClF3C

NO2

33

S2.4: Figure 4 – GC Mass spectrum of compound 13a

Cl

CF3

O2N

34

S2.4: Figure 4 - GC Purity of compound 13a

Cl

CF3

O2N

35


NC

F3CCl

36



NC

F3CCl

37

NC

F3CCl

38

S2.5: Figure 4 - GC Mass spectrum of compound 14a

NC F3C

Cl

39


NC F3C

Cl

40


ClF3C

41


ClF3C

42


Cl

CF3

43


Cl

CF3

44


ClF3C

MeO F

45


ClF3C

MeO F

46

S2.7: Figure 3 – 13C NMR spectrum of compound 16a

ClF3C

MeO F

47

S2.7: Figure 4 - GC MS spectrum of compound 16a

Cl

CF3MeO

F

48


Cl

CF3MeO

F

49


S

F3CCl

50


51


S

F3CCl

52


SCF3

Cl

53


SCF3

Cl

54


ClF3CBr

F

55


ClF3CBr

F

56


ClF3CBr

F

57


Note: Z isomer is not separated due to low concentration (refer - 19F NMR)

Cl

CF3Br

F

58


Note: “Z” isomer is not separated due to low concentration (refer - 19F NMR)

Cl

CF3Br

F

59


ClF3C

Cl Cl

60


ClF3C

Cl Cl

61


ClF3C

Cl Cl

62


Cl

CF3Cl

Cl

63


Cl

CF3Cl

Cl

64

S2.11: Figure 1 - 1H NMR spectrum of compound 20a - A

Br

S

ClF3C

65

S2.11: Figure 2 - 19F NMR spectrum of compound 20a - A

Br

S Cl

CF3

Br

S

ClF3C

66

S2.11: Figure 3 – GC Mass spectrum of compound 20a - A

Br

S Cl

CF3

67

S2.11: Figure 4 - GC purity of compound 20a – A

Br

S Cl

CF3

68

S2.11: Figure 5 - 1H NMR spectrum of compound 20a - B

Br

S

ClF3C

69

S2.11: Figure 6 - 19F NMR spectrum of compound 20a - B

Br

S

ClF3C

70

S2.11: Figure 7 - GC Mass spectrum of compound 20a – B

Br

S Cl

CF3

71

S2.11: Figure 8 - GC purity of compound 20a – B

Br

S Cl

CF3

72


S

ClF3C

73


S

ClF3C

74

S2.12: Figure 3- GC Mass spectrum of compound 21a

S Cl

CF3

75


S Cl

CF3

76


ClF3C

77


ClF3C

78


ClF3C

79


Cl

CF3

80


Cl

CF3

81


Cl

CF3

ClCF3

82


ClCF3

83


Cl

CF3

Cl

CF3

84


Cl

CF3

85


Cl

CF3

86


Cl

CF3

F3CCl

H

87


CF3

Cl

H

88


CF3

Cl

H

89


Cl

CF3

F3CCl

H

90


CF3

Cl

H

91


CF3

Cl

H

convenient approach in the synthetic method

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