Ruthenium-catalyzed formation of pyrazoles or 3-hydroxynitriles from propargyl alcohols and hydrazines

Article abstract of DOI:10.24820/ark.5550190.p010.893

Functionalized pyrazoles are generated from secondary propragyl alcohols and hydrazines in a ruthenium-catalyzed cascade process, consisting of redox isomerization, Michael addition, cyclocondensation and dehydrogenation steps. The same bifunctional catalyst mediates the conversion of tertiary propargyl alcohols with hydrazine to 3-hydroxynitriles via anti-Markovnikov hydroamination followed by elimination of ammonia.

Full text of DOI:10.24820/ark.5550190.p010.893

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Ruthenium-catalyzed formation of pyrazoles or 3-hydroxynitriles
from propargyl alcohols and hydrazines
Julia Kaufmann, Elisabeth Jäckel, and Edgar Haak*
Institute of Chemistry, Otto von Guericke University Magdeburg, 39106 Magdeburg, Germany
Email: edgar.haak@ovgu.de
Dedicated to Professor Stephen Hanessian
Received 01-27-2019
Abstract
Accepted 03-08-2019
Published on line 03-13-2019
Functionalized pyrazoles are generated from secondary propragyl alcohols and hydrazines in a ruthenium-
catalyzed cascade process, consisting of redox isomerization, Michael addition, cyclocondensation and
dehydrogenation steps. The same bifunctional catalyst mediates the conversion of tertiary propargyl alcohols
with hydrazine to 3-hydroxynitriles via anti-Markovnikov hydroamination followed by elimination of ammonia.
Keywords: Cascade reactions, homogeneous catalysis, propargyl alcohols, pyrazoles, ruthenium
DOI: https://doi.org/10.24820/ark.5550190.p010.893
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Introduction
The pyrazole nucleus represents a pharmacologically privileged substructure that occurs in numerous
pharmaceutical and agrochemical agents.1-3 Various types of pharmacological properties, such as antibacterial,
antifungal, anticancer, antidepressant, antiinflammatory, anti-tuberculosis, antioxidant as well as antiviral
activity have been described for pyrazole derivatives.1,2 Consequently, a variety of efficient and versatile
synthetic methods have been developed to assemble this structural motif.2-11 The 1,3-dipolar cycloaddition of
diazoalkanes or nitrile imines with olefins and alkynes is limited in terms of the accessibility of the 1,3-
dipoles.2-4 The more frequently applied classical cyclocondensation of hydrazines with 1,3-dicarbonyl
compounds (Knorr synthesis) or acetylenic ketones provides a rapid approach to obtain substituted
pyrazoles.2-7 Alternatively, the more readily available enones can be used, but this requires an additional
oxidation step.2-4,8-11 In this context, ruthenium catalysis is often utilized and various modes of oxidative
catalytic activity are applied, including oxidative C-N coupling,9 hydrogen transfer,10 and visible light
photoredox catalysis.11
Some years ago, we discovered that bifunctional ruthenium cyclopentadienone complexes such as catalyst
1 and derivatives thereof bring about various selective transformations of propargyl alcohols with diverse
nucleophiles. Secondary propargyl alcohols are converted in a redox-isomerization / Michael addition
cascade.12-16 Saturated tertiary substrates generate diverse addition or substitution products,13,15,20 whereas
tertiary 1-alkenyl propargyl alcohols undergo an allylation/cycloisomerization cascade process.13,14,16-20 Herein,
we report on a mechanistically related formation of pyrazoles from secondary propargyl alcohols and
hydrazines as well as the generation of 3-hydroxynitriles from tertiary substrates applying similar reaction
conditions (Scheme 1).
Scheme 1. Conventional pyrazole synthesis and ruthenium catalyzed cascade conversions.
Results and Discussion
The ruthenium-catalyzed conversion of secondary propargyl alcohols 2a-j with hydrazine hydrate led to the
formation of various pyrazoles 3. The cascade reaction proceeds via cycloisomerization, Michael addition,
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cyclocondensation and dehydrogenation steps. Almost quantitative product formation is observed from
substrates 2b-2e containing aryl or sterically demanding alkenyl substituents including terpene-derived
starting materials. Alkyl-substituted substrates 2a and 2f led to small amounts of 3-hydroxynitriles 4 as
byproducts, whereas the hydroamination side product (5) is formed solely from the sterically simplest
derivative 2a. Compounds 2g-2j containing sterically less demanding alkenyl side chains generate
regioisomeric dihydro pyrazoles 6 as the minor components (Scheme 2). No conversion of the propargyl
alcohols is observed in absence of the ruthenium catalyst.
a Reaction time: 15 min for 2a-e, 2g, 2j; 30 min for 2f, 2h, 2i.
Scheme 2. Ruthenium catalyzed synthesis of pyrazoles from secondary propargyl alcohols and hydrazine.
If phenylhydrazine is applied as the nucleophilic component, regioisomeric pyrazoles 7 and 8 are obtained
selectively. Byproduct formation is observed only using the sterically simple substrate 2a. Substrates 2b and 2i
react slowly and some unreacted educt was recovered. Substrate 2a forms isomer 7 as the major compound,
whereas unsaturated side chains led to pyrazoles 8 as the major products (Scheme 3).
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Scheme 3. Formation of regioisomeric pyrazoles from secondary propargyl alcohols and phenyl hydrazine.
The formation of byproduct 4 from hydrazine hydrate and alkyl-substituted propargyl alcohols 2a and 2f
led us to investigate the formation of similar 3-hydroxynitriles 4 from tertiary propargyl alcohols 2k-o. Almost
quantitative product formation is observed from alkyl-substituted substrates 2k and 2l. Propargyl alcohols 2n
and 2o are converted much more slowly and some unreacted educt 2 was recovered. The hydroamination side
product (5) is formed solely from the sterically simple derivative 2m, whereas N-aminopyrroles 10 are
generated as byproducts from substrates 2m-2o containing alkenyl side chains (Scheme 4). The propargyl
alcohols are not converted in absence of the ruthenium catalyst. Only trace amounts of hydroxynitriles 4 are
generated from substituted hydrazines (e.g. phenylhydrazine, tert.-butylhydrazine, N,N-dimethylhydrazine)
and propargyl alcohols 2 applying similar reaction conditions. A related rhodium catalyzed conversion of
tertiary propargyl alcohols with tert.-butylhydrazine was previously reported by Fukumoto et al.21
a Reaction time: 15 min for 2k-m; 30 min for 2n, 2o.
Scheme 4. Ruthenium catalyzed synthesis of 3-hydroxynitriles from tertiary propargyl alcohols and hydrazine.
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In accordance with our previously reported results,12-20 substrate activation occurs by initial formation of
the chelated π-complex I and its subsequent conversion into alkynyl species II. Secondary substrates are
further converted to alkenyl complex III by a 1,2-hydrogen shift. Regioselective nucleophilic attack at the
metalated carbon followed by a cyclocondensation step leads to alkyl complex V that liberates the pyrazole
Scheme 5. Proposed mechanisms for the catalytic transformations.
(3, 8) via β-hydride elimination. Regeneration of the active catalyst occurs by elimination of hydrogen from the
ruthenium hydride VI. If tertiary substrates are applied, the nucleophile already attacks the alkynyl complex II,
also at the metalated carbon atom. Elimination of ammonia from hydrazone species VII regenerates the active
catalyst and liberates the 3-hydroxynitrile (4). Formation of regioisomeric N-substituted pyrazoles 7 occurs
presumably by initial hydrazone formation from intermediate III. Side products 5 and 9 are formed via
nucleophilic attack at the internal carbon atom of alkynyl complex II, if sterically simple substrates (2a, 2m) are
applied. Side products 6 and 10 result from initial nucleophilic attack at the non-metalated double bond, if
alkenyl substituted substrates are applied (Scheme 5).
Conclusions
We present ruthenium-catalyzed one pot transformations of readily available propargyl alcohols with
hydrazines to yield functionalized pyrazoles or 3-hydroxynitriles, selectively. Aldehyde-derived secondary
substrates are converted into pyrazoles in a cascade process, consisting of redox isomerization, Michael
addition, cyclocondensation and dehydrogenation steps. Ketone-derived tertiary substrates form 3-hydroxy-
nitriles via anti-Markovnikov hydroamination followed by elimination of ammonia. The processes are
catalyzed by a bifunctional ruthenium complex containing a redox-coupled cyclopentadienone ligand. Such
transition-metal catalyzed cascade reactions are of special interest in the context of drug discovery. The
incorporation of multiple structural transformations in one process carried out in one pot increases synthetic
efficiency significantly and facilitates the rapid generation of various structural analogues utilizing readily
available starting materials.
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Experimental Section
General Information
All reactions were carried out in a dry atmosphere under argon. The chemicals used were dried and purified
according to common procedures. Products were purified by flash chromatography on silica and identified by
spectroscopic analysis (1H NMR, 13C NMR, IR, MS, HRMS). Multiplicity was determined by DEPT spectra for all
compounds. Infrared spectra were obtained with a Perkin-Elmer FT-IR 2000. NMR spectra were recorded with
a Bruker DPX 400 or a Bruker Avance 600 spectrometer. MS and HRMS data were obtained with a Finnigan
MAT 95 or a Waters Acquity UPLC-MS H-Class. Reactions using microwave irradiation were performed in a
sealed tube with an Anton-Paar Monowave 300 reactor. Catalyst 1 has been prepared previously,12 and its
crystal structure has been solved.13
General catalytic procedure
Catalyst 1 (0.02 mmol) was dissolved in toluene (2 mL) and the propargyl alcohol (1 mmol) and hydrazine
hydrate (2 mmol) or phenylhydrazine (1 mmol) were subsequently added. The mixture was heated to 150 °C
for 15-30 minutes using microwave irradiation. Evaporation of the solvent and flash chromatography on silica
(gradient: pentane/ethyl acetate) furnished the purified products as colorless or yellow oils or foams.
Spectral data of compounds 3a,22 3b,23 4a,24 4f,25 4k,26 4l,27 4m,28 4n,28 4o,29 7a,30 7b,31 8a,30 and 8b32 are in
agreement with the data previously reported by others.
(E)-3-Styryl-1H-pyrazole (3c). 1H NMR (600 MHz, CDCl3): δ 7.53 (d, J 2.2 Hz, 1H), 7.47 (t, J 7.6 Hz, 2H), 7.33 (t, J
7.4 Hz, 2H), 7.24 (tt, J 7.3, 1.3 Hz, 1H), 7.12 (d, J 16.6 Hz, 1H), 7.08 (d, J 16.6 Hz, 1H), 6.47 (d, J 2.2 Hz, 1H). 13C
NMR (150 MHz, CDCl3): δ 146.7 (br, C), 136.8 (C, C2), 133.9 (br, CH), 130.5 (CH), 128.7 (2CH), 127.9 (CH), 126.4
(2CH), 118.2 (br, CH), 102.6 (CH). IR (ATR): νmax 3181, 3035, 2956, 1672, 1467, 1369, 1205, 1098, 1048, 966,
768, 752, 694 cm-1. MS (EI): m/z (%): 170 [M]+ (86), 169 (100), 142 (22), 84 (50). HRMS (EI): m/z calcd. for
C11H10N2 [M]+: 170.0839; Found: 170.0839.
1
3-((1R,5S)-6,6-Dimethylbicyclo[3.1.1]hept-2-en-2-yl)-1H-pyrazole (3d). H-NMR (600 MHz, CDCl3): δ 7.50 (d,
J 2.1 Hz, 1H), 6.27 (d, J 2.1 Hz, 1H), 6.04 (tt, J 3.2, 1.5 Hz, 1H), 2.74 (td, J 5.6, 1.5 Hz, 1H), 2.50 (dt, J 8.7, 5.6 Hz,
1H), 2.46 (dt, J 18.6, 3.2 Hz, 1H), 2.39 (dt, J 18.6, 3.0 Hz, 1H), 2.20-2.15 (m, 1H), 1.36 (s, 3H), 1.29 (d, J 8.7 Hz,
1H), 0.87 (s, 3H). 13C-NMR (150 MHz, CDCl3): δ 147.2 (br, C), 138.3 (C), 135.5 (br, CH), 120.1 (CH), 101.5 (CH),
44.0 (CH), 40.8 (CH), 38.1 (C), 31.8 (CH2), 31.5 (CH), 26.3 (CH3), 21.0 (CH3). IR: νmax 3215, 2917, 2872, 1666,
1465, 1365, 1195, 1102, 1050, 909, 886, 765, 730, 647. MS (ESI): m/z (%): 188 [M]+ (76), 173 (74), 146 (31),
145 (100), 144 (39), 107 (33), 84 (95). HRMS (EI): m/z calcd. for C12H16N2 [M]+: 188.1308; Found: 188.1308.
1
(S)-3-[4-(Prop-1-en-2-yl)cyclohex-1-en-1-yl]-1H-pyrazole (3e). H-NMR (600 MHz, CDCl3): δ 7.52 (d, J 2.1 Hz,
1H), 6.32 (br s, 1H), 6.31 (d, J 2.1 Hz, 1H), 4.80-4.77 (m, 2H), 2.65-2.58 (m, 1H), 2.51-2.41 (m, 1H), 2.37-2.22 (m,
2H), 2.18-2.09 (m, 1H), 2.00-1.94 (m, 1H), 1.80 (s, 3H), 1.61 (dtd, J 12.7, 11.3, 5.5 Hz, 1H). 13C-NMR (150 MHz,
CDCl3): δ 149.5 (C), 148.4 (br, C), 134.9 (br, CH), 128.0 (C), 124.3 (CH), 108.9 (CH2), 101.2 (CH), 40.8 (CH), 30.9
(CH2), 27.6 (CH2), 26.8 (CH2), 20.9 (CH3). IR: νmax 3184, 3082, 2920, 1644, 1451, 1434, 1373, 1284, 1198, 1107,
1050, 934, 885, 831, 761 cm-1. MS (EI): m/z (%): 188 [M]+ (67), 147 (61), 120 (77), 119 (100), 93 (59), 81 (33).
HRMS (EI): m/z calcd. for C12H16N2 [M]+: 188.1308; Found 188.1308.
3-Pentyl-1H-pyrazole (3f). 1H NMR (600 MHz, CDCl3): δ 7.50 (d, J 1.9 Hz, 1H), 6.09 (d, J 1.9 Hz, 1H), 2.69 (t, J 7.8
Hz, 2H), 1.68 (br quint, J 7.6 Hz, 2H), 1.36-1.34 (m, 4H), 0.91 (t, J 7.0 Hz, 1H). 13C NMR (150 MHz, CDCl3): δ
147.9 (br, C), 135.1 (br, CH), 103.4 (CH), 31.6 (CH2), 29.2 (CH2), 26.7 (CH2), 22.5 (CH2), 14.1 (CH3). IR (ATR): νmax
3194, 2955, 2928, 2867, 2859, 1686, 1466, 1434, 1377, 1295, 1202, 1111, 1050, 933, 827, 757 cm-1. MS (EI):
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m/z (%): 138 [M]+ (82), 109 (59), 96 (79), 95 (91), 83 (82), 82 (100), 81 (92). HRMS (EI): m/z calcd. for C8H14N2
[M]+: 138.1152; Found: 138.1152.
(E)-3-(Prop-1-en-1-yl)-1H-pyrazole (3g). 1H NMR (600 MHz, CDCl3): δ 7.50 (d, J 2.1 Hz, 1H), 6.40 (dq, J 16.0, 1.7
Hz, 1H), 6.30 (d, J 2.1 Hz, 1H), 6.24 (dq, J 15.9, 6.6 Hz, 1H), 1.89 (dd, J 6.6, 1.6 Hz, 3H). 13C NMR (150 MHz,
CDCl3): δ 146.6 (br, C), 134.5 (br, CH), 128.3 (CH), 120.9 (CH), 102.0 (CH), 18.6 (CH3). HRMS (EI): m/z calcd. for
C6H8N2 [M]+: 108.0682; Found: 108.0683.
3-(2,6-Dimethylhepta-1,5-dien-1-yl)-1H-pyrazole (3h). E-Isomer: 1H NMR (600 MHz, CDCl3): δ 7.56 (d, J 2.0 Hz,
1H), 6.29 (d, J 2.0 Hz, 1H), 6.22 (br s, 1H), 5.16-5.13 (m, 1H), 2.21-2.17 (m, 4H), 1.96 (d, J 1.2 Hz, 3H), 1.70 (br s,
3H), 1.63 (br s, 3H). 13C NMR (150 MHz, CDCl3): δ 143.9 (br, C), 141.6 (C), 136.1 (br, CH), 132.1 (C), 123.7 (CH),
113.9 (CH), 104.3 (CH), 40.9 (CH2), 26.7 (CH2), 25.8 (CH3), 18.6 (CH3), 17.8 (CH3). IR (ATR): νmax 3186, 3110,
2967, 2855, 1660, 1447, 1376, 1275, 1206, 1169, 1107, 1050, 934, 868, 756 cm-1. HRMS (EI): m/z calcd. for
1
C12H18N2: 190.1465 [M]+; found: 190.1465. Z-Isomer: H NMR (600 MHz, CDCl3): δ 7.54 (d, J 1.8 Hz, 1H), 6.24
(d, J 1.8 Hz, 1H), 6.17 (br s, 1H), 5.19-5.17 (m, 1H), 2.35 (dd, J 8.3, 7.4 Hz, 2H), 2.22-2.19 (m, 2H), 1.92 (d, J 1.1
Hz, 3H), 1.71 (br s, 3H), 1.64 (br s, 3H). 13C NMR (150 MHz, CDCl3): δ 143.3 (br, C), 142.8 (C), 137.2 (br, CH),
132.9 (C), 124.1 (CH), 114.5 (CH), 104.4 (CH), 33.9 (CH2), 26.4 (CH2), 26.1 (CH3), 24.8 (CH3), 18.1 (CH3). HRMS
(EI): m/z calcd. for C12H18N2: 190.1465 [M]+; found: 190.1466.
3-(2-Methylprop-1-en-1-yl)-1H-pyrazole (3i). 1H NMR (600 MHz, CDCl3): δ 7.55 (d, J 1.8 Hz, 1H), 6.27 (d, J 1.8
Hz, 1H), 6.20 (br s, 1H), 1.96 (d, J 0.7 Hz, 3H), 1.93 (d, J 1.1 Hz, 3H). 13C NMR (150 MHz, CDCl3): δ 143.9 (br, C),
138.4 (C), 136.3 (br, CH), 114.2 (CH), 104.3 (CH), 27.1 (CH3), 20.1 (CH3). IR (ATR): νmax 3179, 3101, 2927, 1665,
1462, 1441, 1377, 1280, 1207, 1109, 1051, 934, 839, 761 cm-1. MS (EI): m/z (%): 122 [M]+ (100), 107 (27), 94
(20); HRMS (EI): m/z calcd. for C7H10N2: 122.0839 [M]+; Found: 122.0838.
(E)-3-(Pent-1-en-1-yl)-1H-pyrazole (3j). 1H NMR (600 MHz, CDCl3): δ 7.51 (d, J 2.1 Hz, 1H), 6.40 (dt, J 16.0, 1.3
Hz, 1H), 6.32 (d, J 2.1 Hz, 1H), 6.25 (dt, J 16.0, 6.9 Hz, 1H), 2.19 (qd, J 7.1, 1.3 Hz, 2H), 1.50 (sext, J 7.4 Hz, 2H),
0.96 (t, J 7.4 Hz, 3H). 13C NMR (150 MHz, CDCl3): δ 146.5 (br, C), 134.6 (br, CH), 133.4 (CH), 119.7 (CH), 102.0
(CH), 35.1 (CH2), 22.4 (CH2), 13.8 (CH3). IR (ATR): νmax 3175, 3100, 2958, 2928, 2871, 1662, 1462, 1436, 1377,
1296, 1200, 1102, 1052, 962, 934, 759 cm-1. MS (EI): m/z (%): 136 [M]+ (94), 121 (62), 107 (100), 94 (49), 80
(69). HRMS (EI): m/z calcd. for C8H12N2: 136.0995 [M]+; Found: 136.0995.
(E)-1-Phenyl-3-styryl-1H-pyrazole (7c). 1H NMR (600 MHz, CDCl3): δ 7.92 (d, J 2.5 Hz, 1H), 7.73 (dd, J 8.5, 1.1
Hz, 2H), 7.57 (d, J 7.3 Hz, 2H), 7.55 (d, J 7.4 Hz, 2H), 7.48 (dd, J 8.5, 7.5 Hz, 2H), 7.39 (t, J 7.6 Hz, 2H), 7.30 (t, J
7.3 Hz, 1H), 7.29 (t, J 7.5 Hz, 1H), 7.26 (d, J 16.6 Hz, 1H), 7.20 (d, J 16.6 Hz, 1 H), 6.71 (d, J 2.5 Hz, 1H). 13C NMR
(150 MHz, CDCl3): δ 152.4 (C), 140.2 (C), 137.2 (C), 130.9 (CH), 129.6 (2CH), 128.8 (2CH), 128.0 (CH), 127.9
(CH), 126.7 (2CH), 126.5 (CH, C13), 120.6 (CH), 119.1 (2CH), 105.1 (CH). IR (ATR): νmax 3047, 3000, 1598, 1515,
1499, 1381, 1256, 1052, 963, 946, 761, 747, 688 cm-1. MS (EI): m/z (%): 246 [M]+ (84), 245 (100), 169 (39), 168
(31), 158 (39). HRMS (EI): m/z calcd. for C17H14N2 [M]+: 246.1152; Found: 246.1152.
1
3-((1R,5S)-6,6-Dimethylbicyclo[3.1.1]hept-2-en-2-yl)-1-phenyl-1H-pyrazole (7d). H NMR (600 MHz, CDCl3): δ
7.86 (d, J 2.5 Hz, 1H), 7.70 (dd, J 8.7, 1.2 Hz, 2H), 7.44 (dd, J 8.5, 7.4 Hz, 2H), 7.26 (tt, J 7.5, 1.1 Hz, 2H), 6.55 (d,
J 2.5 Hz, 1H), 6.19 (tt, J 3.3, 1.5 Hz, 1H), 3.12 (td, J 5.7, 1.4 Hz, 1H), 2.55 (dt, J 8.8, 5.7 Hz, 1H), 2.51 (dt, J 18.4,
3.2 Hz, 1H), 2.44 (dt, J 18.4, 3.0 Hz, 1H), 2.22 (septd, J 2.9, 1.2 Hz, 1H), 1.41 (s, 3H), 1.34 (d, J 8.9 Hz, 1H), 0.93
(s, 3H). 13C NMR (150 MHz, CDCl3): δ 153.7 (C), 140.9 (C), 140.4 (C), 129.4 (2CH), 127.7 (CH), 126.0 (CH), 120.7
(CH), 119.0 (2CH), 104.1 (CH), 43.0 (CH), 41.0 (CH), 38.0 (C), 32.0 (CH2), 31.6 (CH2), 26.4 (CH3), 21.1 (CH3). IR
(ATR): νmax 2931, 2913, 1599, 1517, 1501, 1461, 1365, 1315, 1254, 1220, 1199, 1176, 1155, 1140, 1121, 1081,
1046, 1029, 946, 927, 902, 885, 807, 751, 689, 667 cm-1. MS (EI): m/z (%): 264 [M]+ (92), 249 (78), 221 (100),
182 (40), 105 (37). HRMS (EI): m/z calcd. for C18H20N2 [M]+: 264.1621; Found: 264.1621.
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(S)-1-Phenyl-3-[4-(prop-1-en-2-yl)cyclohex-1-en-1-yl]-1H-pyrazole (7e). 1H NMR (600 MHz, CDCl3): δ 7.86 (d, J
2.3 Hz, 1H), 7.70 (dd, J 8.5, 1.1 Hz, 2H), 7.44 (dd, J 8.4, 7.4 Hz, 2H), 7.26 (tt, J 7.5, 1.1 Hz, 1H), 6.53 (d, J 2.4 Hz,
1H), 6.43 (dtd, J 5.2, 2.4, 0.9 Hz, 1H), 4.80-4.78 (m, 2H), 2.84-2.79 (m, 1H), 2.56-2.49 (m, 1H), 2.40-2.35 (m,
1H), 2.32-2.27 (m, 1H), 2.17 (dddt, J 17.6, 10.5, 3.9, 2.6 Hz, 1H), 2.02-1.98 (m, 1H), 1.81 (s, 3H), 1.64 (dtd, J
12.7, 11.5, 5.3 Hz, 1H). 13C NMR (150 MHz, CDCl3): δ 154.7 (C), 150.0 (C), 140.4 (C), 130.4 (C), 129.5 (2CH),
127.4 (CH), 126.1 (CH), 124.8 (CH), 118.9 (2CH), 108.9 (CH2), 104.0 (CH), 41.1 (CH), 31.1 (CH2), 27.7 (CH2), 26.5
(CH2), 21.0 (CH3). IR (ATR): νmax 3069, 2964, 2917, 1599, 1515, 1501, 1451, 1434, 1401, 1372, 1346, 1329,
1294, 1254, 1236, 1093, 1039, 948, 886, 830, 750, 688 cm-1. MS (EI): m/z (%): 264 [M]+ (89), 249 (33), 223 (87),
195 (100), 182 (82), 169 (45). HRMS (EI): m/z calcd. for: C18H20N2 [M]+: 264.1621; Found: 264.1621.
(E)-1-Phenyl-3-(prop-1-en-1-yl)-1H-pyrazole (7g). 1H NMR (400 MHz, CDCl3): δ 7.84 (d, J 2.5 Hz, 1H), 7.67 (dd, J
8.5, 1.1 Hz, 2H), 7.44 (dd, J 8.3, 7.5 Hz, 2H), 7.26 (tt, J 7.4, 1.1 Hz, 2H), 6.53 (dq, J 16.0, 1.5 Hz, 1H), 6.51 (d, J 2.5
Hz, 1H), 6.35 (dq, J 15.9, 6.6 Hz, 1H), 1.92 (dd, J 6.6, 1.6 Hz, 1H). 13C NMR (150 MHz, CDCl3): δ 152.7 (C), 140.2
(C), 129.5 (2CH), 128.6 (CH), 127.7 (CH), 126.2 (CH), 123.2 (CH), 119.0 (2CH), 104.4 (CH), 18.6 (CH3). IR (ATR):
νmax 3048, 3013, 2962, 2931, 2912, 1598, 1518, 1500, 1457, 1386, 1369, 1257, 1048, 963, 949, 930, 750, 689
cm-1. MS (EI): m/z (%): 184 [M]+ (100), 183 (29), 77 (39). HRMS (EI): m/z calcd. for C12H12N2 [M]+: 184.0995;
Found: 184.0995.
(E)-3-(Pent-1-en-1-yl)-1-phenyl-1H-pyrazole (7j). 1H NMR (400 MHz, CDCl3): δ 7.84 (d, J 2.5 Hz, 1H), 7.68 (dd, J
8.5, 1.3 Hz, 1H), 7.44 (dd, J 8.5, 7.5 Hz, 2H), 7.26 (tt, J 7.4, 1.1 Hz, 1H), 6.53 (dt, J 16.0, 1.4 Hz, 1H), 6.52 (d, J 2.5
Hz, 1H), 6.34 (dt, J 16.0, 6.9 Hz, 1H), 2.23 (qd, J 7.0, 1.4 Hz, 2H), 1.53 (sext, J 7.4 Hz, 2H), 0.98 (t, J 7.3 Hz, 3H).
13C NMR (150 MHz, CDCl3): δ 152.8 (C), 140.3 (C), 133.8 (CH), 129.5 (2CH), 127.6 (CH), 126.2 (CH), 122.1 (CH),
118.9 (2CH), 104.5 (CH), 35.1 (CH2), 22.4 (CH2), 13.9 (CH3). IR (ATR): νmax 3047, 2958, 2928, 1599, 1518, 1501,
1456, 1257, 1046, 965, 947, 749, 689 cm-1. MS (EI): m/z (%): 212 [M]+ (100), 197 (80), 183 (38), 131 (34), 77
(31). HRMS (EI): m/z calcd. for C14H16N2 [M]+: 212.1308; Found: 212.1308.
(E)-1-Phenyl-5-styryl-1H-pyrazole (8c). 1H NMR (600 MHz, CDCl3): δ 7.69 (d, J 1.9 Hz, 1H), 7.53 (d, J 4.3 Hz, 4H),
7.45 (q, J 4.3 Hz, 1H), 7.43 (d, J 7.9 Hz, 2H), 7.35 (t, J 7.6 Hz, 2 H), 7.29 (tt, J 7.4, 1.1 Hz, 1H), 7.11 (d, J 16.3 Hz,
1H), 6.92 (d, J 16.3 Hz, 1 H), 6.69 (d, J 1.9 Hz, 1H). 13C NMR (150 MHz, CDCl3): δ 141.3 (C), 140.4 (CH), 139.7 (C),
136.5 (C), 132.2 (CH), 129.3 (2CH), 128.9 (2CH), 128.4 (CH), 128.1 (CH), 126.7 (2CH), 125.6 (2CH), 115.8 (CH),
104.2 (CH). IR (ATR): νmax 3046, 3026, 3002, 1598, 1515, 1499, 1455, 1389, 1328, 1256, 1237, 1071, 1052, 962,
946, 925, 761, 747, 689 cm-1. MS (EI): m/z (%): 246 [M]+ (100), 245 (97), 169 (34), 158 (85), 157 (62). HRMS
(EI): m/z calcd. for C17H14N2 [M]+: 246.1152; Found: 246.1152.
5-((1R,5S)-6,6-Dimethylbicyclo[3.1.1]hept-2-en-2-yl)-1-phenyl-1H-pyrazole (8d). 1H NMR (600 MHz, CDCl3): δ
7.60 (d, J 1.9 Hz, 1H), 7.47 (dd, J 8.5, 1.2 Hz, 2H), 7.42 (t, J 7.9 Hz, 2H), 7.34 (tt, J 7.3, 1.3 Hz, 1H), 6.25 (d, J 1.9
Hz, 1H), 5.75 (tt, J 3.3, 1.4 Hz, 1H), 2.40 (dt, J 18.6, 3.1 Hz, 1H), 2.31 (dt, J 8.8, 5.7 Hz, 1H), 2.29 (dt, J 18.6, 3.1,
1H), 2.11-2.08 (m, 1H), 2.07 (td, J 5.6, 1.5 Hz, 1H), 1.25 (d, J 8.8 Hz, 1H), 1.18 (s, 3H), 0.87 (s, 3H). 13C NMR (150
MHz, CDCl3): δ 144.1 (C), 141.0 (C), 140.1 (CH), 137.6 (C), 129.0 (2CH), 127.6 (CH), 125.2 (CH), 124.9 (2CH),
106.2 (CH), 45.8 (CH), 40.2 (CH), 38.0 (C), 32.1 (CH2), 31.9 (CH2), 26.2 (CH3), 20.9 (CH3). IR (ATR): νmax 2946,
2933, 2915, 1597, 1499, 1468, 1448, 1383, 1366, 1349, 1263, 1219, 1117, 1070, 1055, 1021, 952, 924, 900,
885, 811, 778, 760, 691, 652 cm-1. MS (EI): m/z (%): 264 [M]+ (64), 221 (100), 195 (58), 194 (51), 94 (25). HRMS
(EI): m/z calcd. for: C18H20N2 [M]+: 264.1621; Found: 264.1621.
(S)-1-Phenyl-5-[4-(prop-1-en-2-yl)cyclohex-1-en-1-yl]-1H-pyrazole (8e). 1H NMR (600 MHz, CDCl3): δ 7.62 (d, J
1.9 Hz, 1H), 7.49 (dd, J 8.3, 1.0 Hz, 2H), 7.43 (t, J 7.9 Hz, 2H), 7.35 (tt, J 7.4, 1.2 Hz, 1H), 6.28 (d, J 1.8 Hz, 1H),
5.87-5.85 (m, 1H), 4.79 (quint, J 1.4 Hz, 1H), 4.72-4.71 (m, 1H), 2.27-2.21 (m, 1H), 2.20-2.16 (m, 1H), 2.15-2.10
(m, 2H), 2.07-2.01 (m, 1H), 1.82-1.78 (m, 1H), 1.74 (s, 3H), 1.49 (dddd, J 12.8, 11.2, 10.1, 6.1 Hz, 1H). 13C NMR
(150 MHz, CDCl3): δ 149.3 (C), 145.1 (C), 140.9 (C), 139.9 (CH), 130.0 (CH), 129.1 (2CH), 128.0 (C), 127.5 (CH),
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124.6 (2CH), 109.1 (CH2), 106.5 (CH), 40.3 (CH), 31.0 (CH2), 28.5 (CH2), 27.5 (CH2), 20.9 (CH3). IR (ATR): νmax
3046, 2964, 2917, 1597, 1515, 1500, 1473, 1449, 1384, 1328, 1312, 1258, 1229, 1122, 1070, 1052, 963, 945,
925, 889, 833, 760, 690, 651 cm-1. MS (EI): m/z (%): 264 [M]+ (77), 263 (44), 196 (33), 195 (92), 94 (100). HRMS
(EI): m/z calcd. for: C18H20N2 [M]+: 264.1621; Found: 264.1621.
(E)-1-Phenyl-5-(prop-1-en-1-yl)-1H-pyrazole (8g). 1H NMR (600 MHz, CDCl3): δ 7.59 (d, J 1.9 Hz, 1H), 7.51-7.44
(m, 4H), 7.42-7.38 (m, 1H), 6.47 (d, J 1.9 Hz, 1H), 6.32-6.21 (m, 2H), 1.85 (d, J 4.9 Hz, 3H). 13C NMR (150 MHz,
CDCl3): δ 141.5 (C), 140.2 (CH), 139.8 (C), 130.2 (CH), 129.2 (2CH), 127.9 (CH), 125.5 (2CH), 118.9 (CH), 103.6
(CH), 18.7 (CH3). IR (ATR): νmax 3033, 2963, 2933, 1596, 1499, 1452, 1391, 1070, 956, 931, 924, 910, 761, 695,
684, 648 cm-1. MS (EI): m/z (%): 184 [M]+ (100), 183 (35), 77 (33). HRMS (EI): m/z calcd. for C12H12N2: 184.0995
[M]+; Found: 184.0995.
5-(2-Methylprop-1-en-1-yl)-1-phenyl-1H-pyrazole (8i). 1H NMR (600 MHz, CDCl3): δ 7.65 (d, J 1.8 Hz, 1H), 7.48
(dd, J 8.4, 1.1 Hz, 2H), 7.43 (t, J 7.6 Hz, 2H), 7.34 (tt, J 7.4, 1.2 Hz, 1H), 6.37 (d, J 1.8 Hz, 1H), 5.97 (br s, 1H), 1.92
(d, J 1.0 Hz, 3H), 1.86 (d, J 1.2 Hz, 3H). 13C NMR (150 MHz, CDCl3): δ 140.1 (C), 140.0 (C), 139.9 (CH), 139.4 (C),
129.0 (2CH), 127.5 (CH), 125.2 (2CH), 113.5 (CH), 106.9 (CH), 26.8 (CH3), 20.1 (CH3). HRMS (EI): m/z calcd. for
C13H14N2: 198.1152 [M]+; Found: 198.1152.
1
(E)-5-(Pent-1-en-1-yl)-1-phenyl-1H-pyrazole (8j). H NMR (400 MHz, CDCl3): δ 7.60 (d, J 1.9 Hz, 1H), 7.51-7.45
(m, 4H), 7.42-7.38 (m, 1H), 6.48 (d, J 1.9 Hz, 1H), 6.30-6.20 (m, 2H), 2.18-2.13 (m, 2H), 1.47 (sext, J 7.3 Hz, 2H),
0.94 (t, J 7.4 Hz, 3H). 13C NMR (150 MHz, CDCl3): δ 141.5 (C), 140.2 (CH), 139.8 (C), 135.3 (CH), 129.2 (2CH),
127.8 (CH), 125.5 (2CH), 117.8 (CH), 103.6 (CH), 35.2 (CH2), 22.3 (CH2), 13.8 (CH3). IR (ATR): νmax 3034, 2958,
2929, 1598, 1500, 1448, 1391, 961, 931, 924, 761, 695, 685, 649 cm-1. MS (EI): m/z (%): 212 [M]+ (70), 208 (30),
183 (70), 169 (100), 131 (33), 77 (45). HRMS (EI): m/z calcd. for C14H16N2 [M]+: 212.1308; Found: 212.1308.
Acknowledgements
This work was supported by the German Research Foundation DFG (No. 265182801).
Supplementary Material
See the Supporting Information for full experimental data and copies of 1H and 13C NMR spectra.
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