Triphenylphosphine catalyzed stereoselective addition of 3,5-diphenyl-1h-pyrazole to acetylenic esters

Article abstract of DOI:10.1080/10426500701557336

Protonation of the highly reactive 1:1 intermediates produced in the reaction between triphenylphosphine and dialkyl acetylenedicarboxylates by 3,5-diphenyl-1H-pyrazole leads to vinyltriphenylphosphonium salts. The cation in these salts undergoes an addit

Full text of DOI:10.1080/10426500701557336

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Phosphorus, Sulfur, and Silicon
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Triphenylphosphine Catalyzed
Stereoselective Addition of
3,5-Diphenyl-1H-pyrazole to
Acetylenic Esters
Nader Noshiranzadeh a & Ali Ramazani a
a Department of Chemistry , University of Zanjan ,
Zanjan, Iran
Published online: 20 Feb 2008.
To cite this article: Nader Noshiranzadeh & Ali Ramazani (2007) Triphenylphosphine
Catalyzed Stereoselective Addition of 3,5-Diphenyl-1H-pyrazole to Acetylenic Esters,
Phosphorus, Sulfur, and Silicon and the Related Elements, 183:1, 144-149, DOI:
10.1080/10426500701557336
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Phosphorus, Sulfur, and Silicon, 183:144–149, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701557336
Triphenylphosphine Catalyzed Stereoselective Addition
of 3,5-Diphenyl-1H-pyrazole to Acetylenic Esters
Nader Noshiranzadeh and Ali Ramazani
Department of Chemistry, University of Zanjan, Zanjan, Iran
Protonation of the highly reactive 1:1 intermediates produced in the reaction be-
tween triphenylphosphine and dialkyl acetylenedicarboxylates by 3,5-diphenyl-1H-
pyrazole leads to vinyltriphenylphosphonium salts. The cation in these salts under-
goes an addition reaction with the counter anion in CH2 Cl2 at room temperature to
yield the corresponding stabilized phosphorus ylides. Elimination of triphenylphos-
phine from the stabilized phosphorus ylides leads to the corresponding electron-poor
N-vinyl pyrazoles in fairly high yields. The reaction is fairly stereoselective.
Keywords Catalyst; dialkyl acetylenedicarboxylates; electron-poor N-vinyl pyrazoles;
phosphorus ylide; triphenylphosphine; vinyltriphenylphosphonium salts
INTRODUCTION
Pyrazole derivatives are in general well-known nitrogen-containing
heterocyclic compounds, and various procedures have been developed
for their syntheses.1−5 The chemistry of pyrazole derivatives have been
the subject of much interest due to their importance for various ap-
plications and their widespread potential and proven biological and
pharmacological activities such as anti-inflammatory, antipyretic, anal-
gesic, antimicrobial, antiviral, antitumor, antifungal, pesticidal, anti-
convulsant, antihistaminic, antibiotics, anti-depressant, and CNS reg-
ulant properties.2−11
β-Additions of nucleophiles to the vinyl group of vinylic phosphonium
salts leading to the formation of new alkylidenephosphoranes has at-
tracted much attention as a very convenient and synthetically useful
method in organic synthesis.12,13 Organophosphorus compounds have
Received 5 May 2007; accepted 5 June 2007.
This work was supported by the Sandoogh Hemayate as Pajuoheshgharane Keshvare
Iran.
Address correspondence to Ali Ramazani, Department of Chemistry, University of
Zanjan, P.O. Box 45195-313, Zanjan, Iran. E-mail: aliramazani@yahoo.com
144

Triphenylphosphine Catalyzed Stereoselective Addition
145
been extensively employed in organic synthesis as useful reagents as
well as ligands in a number of transition metal catalysts.14 Phospho-
rus ylides are a class of special type of zwitterions, which bear strongly
nucleophilic electron rich carbanions. The electron distribution around
the P+ C− bond and its consequent chemical implications had been
probed and assessed through theoretical, spectroscopic and crystallo-
graphic investigations.15 They are excellent ligands and excel in their
ligating functions the unstabilized ylides because of their ambidentate
and chemically differentiating character. Proton affinity of these ylides
can be used as a molecular guide to assess their utility as synthetic
reagents and their function as ligands in coordination and organometal-
lic chemistry.16 The nucleophilicity at the ylidic carbon is a factor of
essential mechanistic importance in the use of these ylides as Wittig
reagents. Phosphorus ylides are important reagents in synthetic or-
ganic chemistry, especially in the synthesis of naturally occurring prod-
ucts, compounds with biological and pharmacological activity.12 These
ylides are usually prepared by treatment of a phosphonium salt with
a base, and phosphonium salts are usually obtained from a phosphine
and an alkyl halide. Phosphonium salts are also prepared by Michael
addition of phosphorus nucleophiles to activated olefins and in other
ways.12 The phosphonium salts are most often converted to the ylide
by treatment with a strong base, though weaker bases can be used if
the salt is acidic enough.12 In recent years, we have established a one-
pot method for the synthesis of stabilized ylides.17−25 In this article, we
wish to describe the stereoselective preparation of electron-poor N-vinyl
pyrazoles from the dialkyl acetylenedicarboxylates and 3,5-diphenyl-
1H-pyrazole in the presence of triphenylphosphine in fairly high yields
(Scheme 1).
RESULTS AND DISCUSSION
Reactions are known in which an α, β-unsaturated carbonyl compound
is produced from phosphonium salts.25 Thus, The compound 5 may re-
sult from initial addition of triphenylphosphine (1) to the acetylenic
esters 2 and concomitant protonation of the 1:1 adducts by the 3,5-
diphenyl-1H-pyrazole (3) to form the corresponding triphenylphospho-
nium salts 4. Addition of the anion in 4 to the vinyltriphenylphos-
phonium cation leads to the formation of the stabilized phosphorus
ylides 5 (Scheme 1) that undergoes intramolecular proton transfer lead-
ing to formation of sterically congested electron-poorN-vinyl pyrazoles
7 via zwitterionic intermediate 6 (Scheme 1). In this reaction triph-
enylphosphine acts as a catalyst. TLC indicated that the reaction was
completed after 72 h in CH2Cl2 at room temperature. We reduced the

146
N. Noshiranzadeh and A. Ramanzani
SCHEME 1
amount of triphenylphosphine to 50% of mole ratio. In all cases where
we have used triphenylphosphine as a catalyst in the range of 50% to
100% of molar ratio, the reaction time amounted to 72 h. In all cases
where we have used triphenylphosphine as a catalyst in the range be-
low 50% of mole ratio, the reaction time was longer than 72 h. The
reaction proceeds smoothly and cleanly and no side reactions were
observed. In the absence of triphenylphosphine no products were ob-
served. Based on TLC monitoring of the reaction and NMR analyses

Triphenylphosphine Catalyzed Stereoselective Addition
147
of the products, in this reaction, Z and E stereoisomers of 7a and 7b
were observed. Relative population of E and Z isomers were deter-
1
mined via their H NMR spectra (7a: %Z = 59 , %E = 41 ; 7b: %Z
= 71, %E = 29) and therefore, the reaction is fairly stereoselective.
The mechanism of the reaction has not been established experimen-
tally and therefore only proposed mechanism is shown in the Scheme
1
1. The structures 7a–b were deduced from their IR, H and 13C NMR
spectra.
CONCLUSION
In summary, we have found a new and efficient method for prepar-
ing sterically congested electron-poorN-vinyl pyrazoles (7) from
triphenylphosphine (1), dialkyl acetylenedicarboxylates (2) and 3,5-
diphenyl-1H-pyrazole (3) (Scheme 1). We believe the reported method
offers a simple and efficient route for the preparation of substi-
tuted electron-poorN-vinyl pyrazole 7a–b (Scheme 1). Its ease of
work up and fairly good yields make it a useful addition to mod-
ern synthetic methodologies. Other aspects of this process are under
investigation.
EXPERIMENTAL
Melting points were measured on an Electrothermal 9100 apparatus
and are uncorrected. IR spectra were recorded on a Mattson-1000 FTIR
1
spectrophotometer. H and 13C NMR spectra were measured with a
Bruker Spectrospin spectrometer at 250 and 62.5 MHz, respectively
(Me4Si as internal standard).
General Procedure for the Preparation of Compounds 7a–b
To a magnetically stirred solution of triphenylphosphine 1 (0.262 g, 1
mmol) and the 3,5-diphenyl-1H-pyrazole 3 (0.22 g, 1 mmol) in CH2Cl2 (5
mL) was added dropwise a mixture of the respective dialkyl acetylenedi-
carboxylate 2 (0.13 mL, 1 mmol) in CH2Cl2 (2 mL) at −10◦C over a
period of 15 min. The mixture was allowed to warm up to room tem-
perature and stirred for 74 h. The solvent was removed under reduced
pressure, and the viscous residue was purified by silica gel column chro-
matography using ethyl acetate-light petroleum ether (1:8) as eluent.
The solvent was removed under reduced pressure yielding the N-vinyl
pyrazoles (7a–b).

148
N. Noshiranzadeh and A. Ramanzani
Dimethyl 2-(3,5-Diphenyl-1H-pyrazol-1-yl)-2-butenedioate (7a)
Colorless oil; yield 75%; IR (neat) (υmax , cm−1): 3026 (CH, arom); 2954
(CH , alipha); 1727 (C O , ester); 1612 (C C, alkene); 1524 (C N). %E
=41, %Z = 59.
1H NMR (CDCl3) for E stereoisomer δH: 3.66 and 3.73 (6 H, 2s, 2
OCH3); 6.15 (1 H, 1 s, CH); 6.76 (1 H, 1 s, H-pyrazol); 7.26–7.88 (10
H, m, arom.).
13C NMR (CDCl3) for E stereoisomer δC : 52.31 and 52.89 (2 OCH3);
107.98, 126.13, 127.86, 128.75, 129.09 (12CH); 129.40, 142.13, 146.11,
153.46 (5C); 162.95 and 164.96 (C O of ester).
1H NMR (CDCl3) for Z stereoisomer δH: 3.58 and 3.64 (6H, 2 s,
2OCH3); 6.81(1H, 1s, H-pyrazol); 7.01(1H, 1s, CH); 7.26–7.88(10H,
m, arom).
13C NMR (CDCl3) for Z stereoisomer δC : 52.14 and 53.11(2OCH3);
104.36, 125.88, 128.61, 128.71, 128.85(12CH); 129.44, 137.86, 146.27,
152.85 (5C); 162.95 and 163.86 (C O of ester).
Diethyl 2-(3,5-Diphenyl-1H-pyrazol-1-yl)-2-butenedioate (7b)
Colorless oil; yield 75%, IR (neat) (υmax , cm−1) : 3020 (CH, arom);
2956 (CH , alipha); 1727 (C O , ester); 1612 (C C, alkene); 1524 (C N).
%E =29, %Z = 79.
1H NMR (CDCl3) for E stereoisomer δH: 1.23 and 1.26 (6H, 2s, 3JHH
=
3
7.2 Hz, 2CH3 of 2OEt ) 4.07 and 4.19 (4H, 2q, JHH = 7.2 Hz, 2OCH2
of 2OEt); 6.22 (1H, 1s, H-pyrazol); 6.76 (1H, 1s, CH); 7.33–7.89 (10H,
m, arom).
13C NMR (CDCl3) for E stereoisomer δC: 13.69 and 14.07 (2CH3);
61.12 and 62.29 (2OCH2of 2OEt); 107.66, 126.08, 127.07, 128.70, 128.80
(12CH); 130.28, 132.64, 141.84, 153.30 (5C); 162.42 and 164.47 (C O
of ester).
1H NMR (CDCl3) for Z stereoisomer δH: 1.01 and 1.07 (6H, 2s, 3JHH
=
7.2 Hz, 2CH3 of 2OEt ) 4.02and 4.10 (4H, 2q, 3JHH = 7.2 Hz, 2OCH2 of
2OEt); 6.82 (1H, 1s, H-pyrazol); 7.07 (1H, 1s, CH); 7.33–7.89 (10H, m,
arom).
13C NMR (CDCl3) for Z stereoisomer δC: 13.69 and 13.95 (2CH3);
61.45 and 62.47 (2OCH2of 2OEt); 104.19, 125.82, 127.79, 128.62, 128.80
(12CH); 129.04, 138.10, 146.05, 152.67 (5C); 162.32 and 163.65 (C O
of ester).
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