1

Efficient One-pot Synthesis of 5-Perfluoroalkylpyrazoles by

Cyclization of Hydrazone Dianions

Thang Ngoc Ngo,a Syeda Abida Ejaz,

b Tran Quang Hung,

a Tuan Thanh Dang,

a,d Jamshed Iqbal,

b Joanna

Lecka,e Jean Sévigny,

e Peter Langer

a,c*

a Institut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany. E-mail: peter.langer@uni-

rostock.de; Fax: +49 381 4986412; Tel: +49 381 4986410

b Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad, Pakistan

c Leibniz Institut für Katalyse an der Universität Rostock e. V. (LIKAT), Albert-Einstein-Str. 29a, 18059 Rostock, Germany.

d Organic Chemistry, Institute of Chemical and Engineering Sciences, 8 Biomedical Grove, 07-01 Neuros, Singapore 138665.

E-mail: thanhtuandang@hotmail.com

e Department of Microbiology-Infectiology and Immunology, Faculty of Medicine, Centre de Recherche du CHU de Québec –

Université Laval, Québec, QC, G1V 4G2, Canada

NMR spectra

1,3-diphenyl-5-(trifluoromethyl)-1H-pyrazole (4a): ..................................................................................................3

3-(4-methoxyphenyl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole (4b):.....................................................................5

3-(3-methoxyphenyl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole (4c): .....................................................................7

3-(2-methoxyphenyl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole (4d):.....................................................................9

3-([1,1'-biphenyl]-4-yl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole (4e): ............................................................... 11

1-phenyl-3-(p-tolyl)-5-(trifluoromethyl)-1H-pyrazole (4f): .................................................................................... 12

3-(2-fluorophenyl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole (4g): ...................................................................... 14

3-(4-fluorophenyl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole (4h): ...................................................................... 17

3-(naphthalen-2-yl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole (4i):...................................................................... 19

1-phenyl-5-(trifluoromethyl)-3-(4-(trifluoromethyl)phenyl)-1H-pyrazole (4j): ..................................................... 21

5-(perfluoroethyl)-1,3-diphenyl-1H-pyrazole (4k): ................................................................................................ 23

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2015

2

3-(4-methoxyphenyl)-5-(perfluoroethyl)-1-phenyl-1H-pyrazole (4l): .................................................................... 25

3-(naphthalen-2-yl)-5-(perfluoroethyl)-1-phenyl-1H-pyrazole (4m): ..................................................................... 27

3-([1,1'-biphenyl]-4-yl)-5-(perfluoroethyl)-1-phenyl-1H-pyrazole (4n): ................................................................ 29

5-(perfluoropropyl)-1,3-diphenyl-1H-pyrazole (4o): .............................................................................................. 31

3-(4-methoxyphenyl)-5-(perfluoropropyl)-1-phenyl-1H-pyrazole (4p): ................................................................. 33

Ethyl 3-(4-methoxyphenyl)-5-(trifluoromethyl)-1H-pyrazole-1-carboxylate (4q): ................................................ 35

Ethyl 3-(2-fluorophenyl)-5-(trifluoromethyl)-1H-pyrazole-1-carboxylate (4r): ..................................................... 37

2-phenyl-3-(trifluoromethyl)-4,5,6,7,8,9,10,11,12,13-decahydro-2H-cyclododeca[c]pyrazole (4s): ..................... 39

2-phenyl-3-(trifluoromethyl)-4,5,6,7-tetrahydro-2H-indazole (4t): ........................................................................ 41

2-phenyl-3-(trifluoromethyl)-4,5-dihydro-2H-indazole (4u): ................................................................................. 43

2-phenyl-3-(trifluoromethyl)-4,5-dihydro-2H-benzo[g]indazole (4v): ................................................................... 45

5-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (5a): ................................................................................ 47

5-(4-methoxyphenyl)-3-(perfluoroethyl)-1H-pyrazole (5b):................................................................................... 49

5-(4-methoxyphenyl)-3-(perfluoropropyl)-1H-pyrazole (5c): ................................................................................. 51

5-(naphthalen-2-yl)-3-(trifluoromethyl)-1H-pyrazole (5d): .................................................................................... 53

5-(naphthalen-2-yl)-3-(perfluoroethyl)-1H-pyrazole (5e): ...................................................................................... 55

3-(3,3,3,3,3,3,3-heptafluoro-3l8-prop-1-yn-1-yl)-5-(naphthalen-2-yl)-1H-pyrazole (5f): ...................................... 57

3-(trifluoromethyl)-5-(4-(trifluoromethyl)phenyl)-1H-pyrazole (5g): .................................................................... 59

5-(perfluoroethyl)-3-(4-(trifluoromethyl)phenyl)-1H-pyrazole (5h):...................................................................... 61

3-(3,3,3,3,3,3,3-heptafluoro-3l8-prop-1-yn-1-yl)-5-(4-(trifluoromethyl)phenyl)-1H-pyrazole (5i): ...................... 63

2-phenyl-3-(trifluoromethyl)-2H-indazole (6a): ..................................................................................................... 64

2-phenyl-3-(trifluoromethyl)-2H-benzo[g]indazole (6b): ....................................................................................... 66

3-(4-methoxyphenyl)-5-(trifluoromethyl)isoxazole (8a): ....................................................................................... 68

3-(naphthalen-2-yl)-5-(trifluoromethyl)isoxazole (8b): .......................................................................................... 70

3

1,3-diphenyl-5-(trifluoromethyl)-1H-pyrazole (4a):

4

5

3-(4-methoxyphenyl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole (4b):

6

7

3-(3-methoxyphenyl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole (4c):

8

9

3-(2-methoxyphenyl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole (4d):

10

11

3-([1,1'-biphenyl]-4-yl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole (4e):

12

1-phenyl-3-(p-tolyl)-5-(trifluoromethyl)-1H-pyrazole (4f):

13

14

3-(2-fluorophenyl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole (4g):

15

16

17

3-(4-fluorophenyl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole (4h):

18

19

3-(naphthalen-2-yl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole (4i):

20

21

1-phenyl-5-(trifluoromethyl)-3-(4-(trifluoromethyl)phenyl)-1H-pyrazole (4j):

22

23

5-(perfluoroethyl)-1,3-diphenyl-1H-pyrazole (4k):

24

25

3-(4-methoxyphenyl)-5-(perfluoroethyl)-1-phenyl-1H-pyrazole (4l):

26

27

3-(naphthalen-2-yl)-5-(perfluoroethyl)-1-phenyl-1H-pyrazole (4m):

28

29

3-([1,1'-biphenyl]-4-yl)-5-(perfluoroethyl)-1-phenyl-1H-pyrazole (4n):

30

31

5-(perfluoropropyl)-1,3-diphenyl-1H-pyrazole (4o):

32

33

3-(4-methoxyphenyl)-5-(perfluoropropyl)-1-phenyl-1H-pyrazole (4p):

34

35

Ethyl 3-(4-methoxyphenyl)-5-(trifluoromethyl)-1H-pyrazole-1-carboxylate (4q):

36

37

Ethyl 3-(2-fluorophenyl)-5-(trifluoromethyl)-1H-pyrazole-1-carboxylate (4r):

38

39

2-phenyl-3-(trifluoromethyl)-4,5,6,7,8,9,10,11,12,13-decahydro-2H-cyclododeca[c]pyrazole (4s):

40

41

2-phenyl-3-(trifluoromethyl)-4,5,6,7-tetrahydro-2H-indazole (4t):

42

43

2-phenyl-3-(trifluoromethyl)-4,5-dihydro-2H-indazole (4u):

44

45

2-phenyl-3-(trifluoromethyl)-4,5-dihydro-2H-benzo[g]indazole (4v):

46

47

5-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (5a):

48

49

5-(4-methoxyphenyl)-3-(perfluoroethyl)-1H-pyrazole (5b):

50

51

5-(4-methoxyphenyl)-3-(perfluoropropyl)-1H-pyrazole (5c):

52

53

5-(naphthalen-2-yl)-3-(trifluoromethyl)-1H-pyrazole (5d):

54

55

5-(naphthalen-2-yl)-3-(perfluoroethyl)-1H-pyrazole (5e):

56

57

3-(3,3,3,3,3,3,3-heptafluoro-3l8-prop-1-yn-1-yl)-5-(naphthalen-2-yl)-1H-pyrazole (5f):

58

59

3-(trifluoromethyl)-5-(4-(trifluoromethyl)phenyl)-1H-pyrazole (5g):

60

61

5-(perfluoroethyl)-3-(4-(trifluoromethyl)phenyl)-1H-pyrazole (5h):

62

63

3-(3,3,3,3,3,3,3-heptafluoro-3l8-prop-1-yn-1-yl)-5-(4-(trifluoromethyl)phenyl)-1H-pyrazole (5i):

64

2-phenyl-3-(trifluoromethyl)-2H-indazole (6a):

65

66

2-phenyl-3-(trifluoromethyl)-2H-benzo[g]indazole (6b):

67

68

3-(4-methoxyphenyl)-5-(trifluoromethyl)isoxazole (8a):

69

70

3-(naphthalen-2-yl)-5-(trifluoromethyl)isoxazole (8b):

71