convenient approach in the synthetic method
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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. mohanaroopan.s@vit.ac.inbDepartment 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.
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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.
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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): -
60.99 (s, CF3, -3F, E- isomer), -67.61 (s, CF3, -3F, Z- isomer); GC-MS (ESI 70 eV
+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
1.18 g; Yield: 73%; Colourless liquid; 1H NMR (300 MHz, DMSO-d6): δ 7.77-7.12
(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):
1.03 g; Yield: 64%; Colourless liquid; 1H NMR (300 MHz, DMSO-d6): δ 7.65-7.63
(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): -
60.75 (s, CF3, -3F, E- isomer), -67.29 (s, CF3, -3F, Z- isomer); GC-MS (ESI 70 eV
+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).
1.49 g; Yield: 85%; Colourless liquid; 1H NMR (300 MHz, DMSO-d6): δ 7.70-7.58
(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): -
60.95 (s, CF3, -3F, E- isomer), -67.52 (s, CF3, -3F, Z- isomer); GC-MS (ESI 70 eV
+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:
DBU (2 ml, 128.9 mmol) diluted in 5 ml THF was added to a stirred solution of
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
DBU (2 ml, 128.9 mmol) diluted in 5 ml THF was added to a stirred solution of
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): -
62.06 (s, CF3, -3F, E- isomer), -67.01 (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 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
S2.5: Figure 1 - 1H NMR spectrum of compound 14a
NC
F3CCl
36
S2.5: Figure 2 - 13C NMR spectrum of compound 14a
S2.5: Figure 3 - 19F NMR spectrum of compound 14a
NC
F3CCl
37
NC
F3CCl
38
S2.5: Figure 4 - GC Mass spectrum of compound 14a
NC F3C
Cl
39
S2.5: Figure 5 - GC Purity of compound 14a
NC F3C
Cl
40
S2.6: Figure 1 - 1H NMR spectrum of compound 15a
ClF3C
41
S2.6: Figure 2 - 19F NMR spectrum of compound 15a
ClF3C
42
S2.6: Figure 3 - GC Mass spectrum of compound 15a
Cl
CF3
43
S2.6: Figure 4 - GC Purity of compound 15a
Cl
CF3
44
S2.7: Figure 1 - 1H NMR spectrum of compound 16a
ClF3C
MeO F
45
S2.7: Figure 2 - 19F NMR spectrum of compound 16a
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
S2.7: Figure 5 - GC Purity of compound 16a
Cl
CF3MeO
F
49
S2.8: Figure 1 - 1H NMR spectrum of compound 17a
S
F3CCl
50
S2.8: Figure 2 - 13C NMR spectrum of compound 17a
51
S2.8: Figure 3 - 19F NMR spectrum of compound 17a
S
F3CCl
52
S2.8: Figure 4 - GC Mass spectrum of compound 17a
SCF3
Cl
53
S2.8: Figure 5 - GC Purity of compound 17a
SCF3
Cl
54
S2.9: Figure 1 - 1H NMR spectrum of compound 18a
ClF3CBr
F
55
S2.9: Figure 2 – 13C NMR spectrum of compound 18a
ClF3CBr
F
56
S2.9: Figure 3 - 19F NMR spectrum of compound 18a
ClF3CBr
F
57
S2.9: Figure 4 - GC Mass spectrum of compound 18a
Note: Z isomer is not separated due to low concentration (refer - 19F NMR)
Cl
CF3Br
F
58
S2.9: Figure 5 - GC Purity of compound 18a
Note: “Z” isomer is not separated due to low concentration (refer - 19F NMR)
Cl
CF3Br
F
59
S2.10: Figure 1 - 1H NMR spectrum of compound 19a
ClF3C
Cl Cl
60
S2.10: Figure 2 – 13C NMR spectrum of compound 19a
ClF3C
Cl Cl
61
S2.10: Figure 3 - 19F NMR spectrum of compound 19a
ClF3C
Cl Cl
62
S2.10: Figure 4 - GC Mass spectrum of compound 19a
Cl
CF3Cl
Cl
63
S2.10: Figure 5 - GC Purity of compound 19a
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
S2.12: Figure 1 - 1H NMR spectrum of compound 21a
S
ClF3C
73
S2.12: Figure 2 - 13C NMR spectrum of compound 21a
S
ClF3C
74
S2.12: Figure 3- GC Mass spectrum of compound 21a
S Cl
CF3
75
S2.12: Figure 4 - GC Purity of compound 21a
S Cl
CF3
76
S2.13: Figure 1 - 1H NMR spectrum of compound 22a
ClF3C
77
S2.13: Figure 2 – 13C NMR spectrum of compound 22a
ClF3C
78
S2.13: Figure 3 - 19F NMR spectrum of compound 22a
ClF3C
79
S2.13: Figure 4 - GC Mass spectrum of compound 22a
Cl
CF3
80
S2.13: Figure 5 - GC Purity of compound 22a
Cl
CF3
81
S2.14: Figure 1 - 1H NMR spectrum of compound 23a
Cl
CF3
ClCF3
82
S2.14: Figure 2 – 13C NMR spectrum of compound 23a
ClCF3
83
S2.14: Figure 3 - 19F NMR spectrum of compound 23a
Cl
CF3
Cl
CF3
84
S2.14: Figure 4 - GC Mass spectrum of compound 23a
Cl
CF3
85
S2.14: Figure 5 - GC Purity of compound 23a
Cl
CF3
86
S2.15: Figure 1 - 19F NMR spectrum of compound 24a
Cl
CF3
F3CCl
H
87
S2.15: Figure 2 - GC Mass spectrum of compound 24a
CF3
Cl
H
88
S2.15: Figure 3 - GC Purity of compound 24a
CF3
Cl
H
89
S2.16: Figure 1 - 19F NMR spectrum of compound 25a
Cl
CF3
F3CCl
H
90
S2.16: Figure 2 - GC Mass spectrum of compound 25a
CF3
Cl
H
91
S2.16: Figure 3 - GC Purity of compound 25a
CF3
Cl
H
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