A new method for the synthesis of pyrazolidines

Article abstract of DOI:10.1016/j.tetlet.2016.05.011

Fully protected pyrazolidines can be readily obtained by acid-catalysed cyclisations of the corresponding allylic hydrazines by carbenium ion generation using concentrated sulfuric acid in dichloromethane.

Full text of DOI:10.1016/j.tetlet.2016.05.011

Accepted Manuscript
A new method for the synthesis of pyrazolidines
Faryal Chaudhry, Benson M. Kariuki, David W. Knight
PII:
S0040-4039(16)30520-2
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.05.011
TETL 47625
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
6 April 2016
29 April 2016
4 May 2016
Please cite this article as: Chaudhry, F., Kariuki, B.M., Knight, D.W., A new method for the synthesis of
pyrazolidines, Tetrahedron Letters (2016), doi: http://dx.doi.org/10.1016/j.tetlet.2016.05.011
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A new method for the synthesis of pyrazolidines.
Faryal Chaudhry,1 Benson M. Kariuki and David W. Knight*
School of Chemistry, Cardiff University, Main College, Park Place, Cardiff, CF10 3AT, UK
___________________________________________________________________________________________________________
Abstract- Fully protected pyrazolidines can be readily obtained by acid-catalysed cyclisations of the corresponding allylic
hydrazines by carbenium ion generation using concentrated sulfuric acid in dichloromethane.
Key words: Pyrazolidine; synthesis; acid-catalysed; cyclisation; hydrazines.
___________________________________________________________________________________________________________
Pyrazoles and their partly and fully reduced derivatives, pyrazolines and pyrazolidines, form an important
group of heterocycles, with potentially important contributions to make to drug design by reason of their
ability to form strong hydrogen bonds at either or both nitrogen atoms. It is perhaps also significant that
Nature does not seem able to form N-N bonds directly and hence such compounds will occupy an entirely
non-natural portion of chemical space and hence are likely to continue to play a central role in the discovery
of novel pharmaceuticals.2 Despite the enormous contribution made by heteroaromatic residues, both with
and without incorporated nitrogen atoms in a majority of commercial drug structures, it has recently become
plain that to achieve a continuation of this success, it would be wise to embrace semi-saturated and fully
saturated analogues of such structural features, in order to introduce both greater flexibility and increased
three dimensional shape.2
Many synthetic routes have been defined for the syntheses of such heterocyclic systems, but quite often these
suffer from a lack of regioselectivity, particularly when both C-N bonds are formed effectively
simultaneously from a hydrazine and an all-carbon bis-electrophile such as a 1,3-dicarbonyl or a conjugated
enone.3 Hence, often it is preferable to assemble such structures using a stepwise approach.4,5 The inspiration
for the present methodology was derived from a possible extension of our finding that unsaturated
sulfonamides 1 are readily converted into the corresponding pyrrolidines 2 following exposure to acid,6 in an
intramolecular hydroamination reaction. A particularly rapid and efficient example (Scheme 1) features
favourable tertiary carbenium ion generation by protonation of the alkene group in the precursor sulfonamide
1, which is then trapped by the sulfonamide group to give an essentially quantitative yield of the
corresponding pyrrolidines 2.
0.4 eq. TfOH
or c.H2SO4
R
R
N
HN
Ts
CH2Cl2,
0 oC, ~15 min.
~100%
Ts
1
2
Scheme 1. Intramolecular, acid-catalysed hydroamination.

Such cyclisations are quite general and are also successful when secondary carbenium generation is required.
The fact that concentrated sulfuric acid can be used in less than stoichiometric quantities gives the method
some positive environmental credentials as the only by-product of these usually very clean cyclisations is the
sodium or potassium sulfate generated upon mild, basic work-up. Of course, the highly acidic nature of the
method will impose some restrictions on future applications; thus far, remote alkenes, alkynes, sulfones,
esters and alcohols protected as the corresponding acetates have been found to be stable and not to interfere
with such cyclisations. It was against this background that we wondered if such methodology could be
extended to include cyclisations of suitably protected allylic hydrazines 3 which, if successful, would result
in the definition of a new and perhaps efficient approach to pyrazolidines 4 (Scheme 2).
H+ ?
R3
N R1
HN
R2
N
R3
R1
N
R2
3
4
Scheme 2. The idea: would protected hydrazines cyclise?
Herein, we report our preliminary results, which show that this idea is indeed viable. A recent report strongly
suggested that the methodology shown in Scheme 2 would be successful. In this study, the discovery of
novel, two-step cyclisations was described in which the acylhydrazones 5 having a distal prenyl alkene
underwent conversion into the annulated pyrazolidines 7 (Scheme 3).5 A likely mechanism involves imine
protonation followed by cyclisation to form a cyclohexane which generates exactly the type of tertiary
carbenium ion 6 featured in our pyrrolidine synthesis (Scheme 1), subsequent trapping of which by the newly
generated hydrazine leads to the observed products 7. Of course, as pointed out,5 alternative mechanisms
could well be in operation, but at least a compatibility between such masked hydrazines and an acid-
catalysed reaction looked likely.6
H
N
NHCOAr
6
H
H
N
N
NHCOAr
NHCOAr
5
7
Scheme 3. An acid-catalysed imine cyclisation: possible mechanism.5
We relied on the Mitsunobu reaction7 to obtain suitable substrates for our investigation of the idea shown in
Scheme 2, as outlined in Scheme 4.

i)
ii)
HNCO2Me
NH2
HNCO2Me
NPhth
NCO2Me
NPhth
8
9
10
iii)
v)
iv)
OH
NCO2R
NCO2Me
NH2
NHCO2R
12
11
13
a) R = Me
b) R = iPr
vi)
vii)
NCO2Me
NHZ
NCO2Me
NHTs
14
15
Scheme 4. Starting material synthesis: Reagents and conditions:
i) a) phthalic anhydride, THF, rt, 0.5 h; b) DCC, rt, 18 h, add HOAc
and Et3N, reflux, 1 h (95%); ii) Ph3P, THF, 0 oC, DIAD, 0 oC,
0.25 h, alcohol 12, 0 oC, 0.25 h, add hydrazine 9, then rt, 18 h (87%);
iii) MeNHNH2, CH2Cl2, EtOH, 0 oC-rt, 18 h (96%); iv) K2CO3, Et2O,
H2O, amine 11, add ClCO2Me, rt, 2 h (92%); v) diisopropyl
azodicarboxylate, Ph3P, Et2O, rt, 18 h (ca. 50%); vi) as iv) with
ClCO2Bn (97%); vii) TsCl, pyridine, CH2Cl2, 0-20 oC, 18 h (92%).
Starting with methyl carbazate 8, addition to phthalic anhydride followed by carbodiimide-induced
cyclisation gave the doubly protected hydrazine 9.8 A Mitsunobu coupling of this intermediate with prenyl
alcohol 12 then gave fully substituted hydrazine 10, Ing-Mansk deprotection of which led to the free amine
11. Coupling of this with a chloroformate or tosyl chloride then gave precursors 13a, 14 and 15 in generally
excellent yields. More directly, prenyl alcohol 12 was converted into the symmetrically protected hydrazine
13 by a “half-Mitsunobu” wherein no additional nucleophile is added; the hydrazine by-product plays this
role.9 Although more rapid, this direct method never gave much above a 50% yield after careful
chromatography and hence the lengthier route was preferred. It did however provide useful structural
confirmation of the assigned structures 13 and others. The isomer 17 of the mixed carbamate-sulfonamide
protected hydrazine 15 was prepared by a direct, regioselective Mitsunobu alkylation of alcohol 12.10
ref. 10
HNTs
OH
NTs
+
NHCO2Me
NHCO2Me
12
16
17
Scheme 5: Regioselective Mitsunobu coupling.

The methods shown in Scheme 4 were also used to prepare representative phenyl- 18a-c and a methyl-
substituted hydrazine 19 along with the geranyl derivative 20 using cinnamyl, crotyl and geranyl alcohols
respectively, in similarly good yields (Figure 1).
NR1
NCO2Me
NTs
NHR2
NHCO2Me
NHCO2Me
Ph
18 a) R1 = R2 = CO2Me
b) R1 = CO2Me; R2 = Ts
c) R1 = Ts; R2 = CO2Me
19
20
Figure 1. Hydrazines from cinnamyl, crotyl and geranyl alcohols.
In general, the precursors 13-15 and 17-20 were readily purified by column chromatography and
1
subsequently characterized by the usual criteria. However, line broadening was usually evident in both H
13
and C NMR spectra, due to restricted rotation. For example, at 400 MHz in CDCl3, the symmetrically
protected prenylated hydrazine 13a showed a pair of broad resonances for the NH group (H 6.6 and 6.8) in a
ratio of ca. 2:1 but, when combined, integrating accurately for one proton, together with an indistinct
methylene resonance centred at H 4.04 and one sharp and one slightly broadened methoxy resonances at H
3.65 and 3.63. Similarly, in the 13C NMR spectrum, while the two allylic methyl groups and one of the
methoxy groups appeared as very sharp resonances, the alkene methine (:CH) was slightly broadened and all
remaining resonances were very broad. In practise, once such features became familiar, these served as
highly characteristic patterns enabling identification of such products.
Our initial attempts to carry out the cyclisation summarized in Scheme 2 were focussed on the precursor 13a
as it should be amongst the easiest to convert into a tertiary carbenium ion and also contained robust, acid-
resistant protecting groups. Catalysis of the desired cyclisation using two contrasting acids, concentrated
sulfuric and trifluoromethanesulfonic (triflic) acid, was examined.6 Sulfuric acid is poorly soluble in
dichloromethane, the most suitable solvent for such chemistry so far identified,11 and hence may react in a
quite different manner to freely soluble triflic acid.12
We were pleased to find that stirring the methoxycarbonyl-protected hydrazine 13a with 0.5 equivalent of
concentrated sulfuric acid in dichloromethane12 at ambient temperature overnight resulted in complete
disappearance of the staring material and isolation of a single product 21 in excellent yield. Similar excellent
yields were also obtained but more rapidly by gently refluxing the reaction mixture for three hours or by
using triflic acid, when the cyclisation occurred at ice temperature in around two hours. In all cases, work-up
was simple: the acid was neutralised using saturated aqueous potassium carbonate and the separated organic
layer washed with water then dried (MgSO4) and evaporated.

Table 1. Acid-catalysed cyclisations of hydrazines 13-15 and 17.
Precursor
Conditions
Product
Yield
0.5 eq. c.H2SO4
95%
93%
20 oC, CH2Cl2, 18 h
NCO2Me
NHCO2Me
0.5 eq. c.H2SO4
NCO2Me
40 oC, CH2Cl2, 3 h
N
CO2Me
0.5 eq. TfOH
97%
0 oC, CH2Cl2, 2 h
13a
21
0.5 eq. c.H2SO4
20 oC, CH2Cl2, 22 h
94%
93%
i
NCO2Pr
i
NCO2Pr
i
NHCO2Pr
N
0.5 eq. c.H2SO4
i
40 oC, CH2Cl2, 3 h
CO2Pr
13b
22
NCO2Me
NHZ
0.5 eq. c.H2SO4
96%
NCO2Me
40 oC, CH2Cl2, 3 h
N
Z
14
23
NCO2Me
NHTs
0.5 eq. c.H2SO4
0 oC, CH2Cl2, 1 h
NCO2Me
98%
94%
N
Ts
15
24
0.5 eq. c.H2SO4
NTs
NTs
0 oC, CH2Cl2, <1 h
NHCO2Me
N
CO2Me
17
25
Under more vigorous conditions than these, or if the triflic acid was wet, variable loss of the protecting
groups was evident from NMR spectra of the crude products. The pattern was much the same with
cyclisations of the related bis-isopropyloxycarbonyl derivative 13b, which was converted into the
pyrazolidine 22 under similar conditions. Somewhat to our surprise, the benzyloxycarbonyl (Z) group also
survived heating to 40 oC to give an equallly good yield of the pyrazolidine 23 (Table 1). Exchanging one of
the carbamate groups for a sulfonamide function accelerated the cyclisations, both examples of which (15 
o
24 and 17  25) proceeded rapidly at 0 C. In the case of substrate 15, a lower pKa of the N-H bond to be
broken may be responsible,10 while in the latter example, perhaps greater steric compression due to the tosyl
group assists the conversion to pyrazolidine 25. Overall, the reaction conditions are comsensurate with the
intermediacy of a tertiary carbenium ion and are relatively close to our previous observations.6

Structural proof of the products was straightforward, although there were a few unexpected characteristics.
Disappearance of the resonance for the alkene methine around H 5.2 was the clearest sign of complete
reaction. The products all showed similar degrees of resonance broadening due to restricted and/or pseudo-
1
rotation. For example, in the H NMR spectrum of the pyrazolidine 13a, in CDCl3 at 400 MHz and 32 oC, the
two methoxy groups occurred as sharp singlets at H 3.65 and 3.67, while the geminal methyl groups
appeared as a sharp single resonance at H 1.41. However, the methylene group remote from nitrogen
appeared as a diffuse, broad signal centred on H 1.88 and the two protons of the methylene group adjacent to
nitrogen as two diffuse signals centred at H 3.93 and H 3.18. On warming to 50 oC, the N-CH2 resonances
became very broad but the signal due to the other methylene group resolved into a triplet (H 1.87, J = 6.7
13
Hz). By contrast, when the same sample was used to obtain a C proton-decoupled spectrum under the same
conditions, all resonances were sharp except for the geminal methyl groups, which appeared as very
broadened resonances centred on C 25.3 and 27.4 ppm. Similar effects were observed throughout this series;
in many cases, heating the sample in d6-DMSO produced an even less informative 1H NMR spectrum.
In similar fashion, the mixed carbamate-sulfonamide 24 showed sharp resonances for the tosyl and methoxy
1
o
groups in its H NMR spectrum in CDCl3 at 32 C, but separate, broadened resonances for each of the ring
protons, centred on H 3.64, 3.43, 1.94 and 1.75 and two broadened singlets for the geminal methyls centred
13
at H 1.61 and 0.97. Once again, all resonances in the C spectrum were sharp, except for the methyls which,
as in previous examples, appeared as very broadened resonances centred on 24.2 and 28.3 ppm. To be certain
of these structural assignments, we carried out an X-ray crystallographic analysis of product 24, the result of
which is shown in Figure 2.13
Figure 2. ORTEP diagram of product 24.
We then continued onto a study of related cyclisations of the less highly substituted substrates 18a-c and 19,
each of which would give a less stabilised carbenium ion when protonated at the alkene function (Table 2).
In the event, the cyclisations proceeded well under conditions which correlated well with the stability of the
intermediate carbenium ion. Using either concentrated sulfuric or triflic acid, cyclisations of the
representative cinnamyl derivatives 18a-c either required heating for 3-6 hours in dichloromethane or a more
prolonged reaction time at ambient temperature. At least with these substrates, yields were again excellent.
Table 2. Acid-catalysed cyclisations of hydrazines 18a-c, 19 and 20.

Precursor
Conditions
Product
Yield
93%
96%
0.5 eq. c.H2SO4
40 oC, CH2Cl2, 6 h
NCO2Me
NHCO2Me
NCO2Me
Ph
N
0.5 eq. TfOH
Ph
35 oC, CH2Cl2, 4 h
CO2Me
18a
26
0.5 eq. c.H2SO4
20 oC, CH2Cl2, 44 h
87%
79%
NCO2Me
NHTs
NCO2Me
Ph
N
0.5 eq. c.H2SO4
Ph
Ph
40 oC, CH2Cl2, 3 h
Ts
18b
27
NTs
0.5 eq. c.H2SO4
NTs
95%
90%
Ph
20 oC, CH2Cl2, 40 h
NHCO2Me
N
CO2Me
18c
28
0.5 eq. c.H2SO4
85 oC, (CH2)2Cl2, 22 h
NCO2Me
NCO2Me
NHCO2Me
N
CO2Me
19
29
H
98%
[3:2
t/c]
0.5 eq. c.H2SO4
0 oC, CH2Cl2, 1 h
NTs
NTs
NHCO2Me
N
CO2Me
20
30
Lengthier reaction times again began to cause loss of the protecting groups. In the case of the NHTs
derivative 18b, 18 hours exposure to c.H2SO4 at ambient temperature led to clean conversion but only to an
extent of ca. 50%. In contrast, under both conditions mentioned in Table 2, formation of an isolable by-
product was evident (~25 and 15% respectively), which turned out to be compound 31, formed by
elimination of toluenesulfinic acid. This showed characteristic apparent triplets at H 3.94 and 3.19, along
with other consistent features. Similar elimination products were thought to be present in the crude reaction
mixtures isolated from reactions of the other two cinnamyl-based precursors but were not isolated and
therefore not identified with certainly.
NCO2Me
Ph
N
31
Figure 3. The elimination product from 18b

Predictably, the corresponding crotyl derivative 19 required the much more vigorous conditions of reflux in
dichloroethane in order to induce cyclisation. Nevertheless, a decent yield of the hoped-for pyrazolidine 29
was isolated, but once again there was evidence for the loss of protecting groups although no products from
this were isolated. The products 26-29, in contrast to the foregoing gem-dimethyl derivatives (Table 1),
exhibited largely first order NMR spectra, with only minimal line broadening.
A final example featured an attempt to use a cascade cyclisation to form a bicyclic derivative. As this would
be a return to the intermediacy of tertiary carbenium ions, it was expected to proceed under much milder
conditions. In the event, the geranyl-substituted hydrazine 20 was smoothly converted into a mixture 30 of
two separable products, in a ratio of ca. 3:2, at 0 oC in under one hour. These were assigned as the trans- and
cis-fused products 32 and 33 (Fig. 4), on the basis of some rather poor quality nOe evidence.
H
H
NTs
NTs
N
N
CO2Me
CO2Me
32
33
Figure 4. The trans- and cis-isomers of product 30.
Fortunately, both were crystalline solids and so X-ray crystallographic analysis was used to confirm these
assignments, by measurement of the minor isomer 33, the resulting ORTEP diagram of which is shown in
Figure 5.14
Figure 5. ORTEP diagram of the cis-isomer 33
1
Some resonances were characteristic of the two isomers in their H NMR spectra: in the trans-isomer 32, one
of the protons -to nitrogen appeared as a dd pattern (J = 13.2 and 11.0 Hz) at H 3.22 and a relatively sharp
methoxy signal resonating at H 3.63 whereas in the cis-isomer 33, the corresponding protons resonated as an
apparent triplet (J = 13.0 Hz) at H 3.09 and a very broadened resonance centred on H 3.40.
These model studies have therefore established that the cyclisations shown in Scheme 2 are indeed viable,
despite the presence of two albeit protected nitrogen atoms. Given due attention to the stability or otherwise
of additional substituents, this combination of Mitsunobu coupling or, in the future, other C-N formation

methods and the acid-catalysed cyclisation should provide viable and regiospecific access to many types of
pyrazolidines.
Acknowledgements
We thank Dr Piotr Rutkowski for skilled experimental assistance and advice and the Higher Education
Commission (HEC), Pakistan, for the award of a six month IRSIP fellowship (to FC).
References and notes
1.
2.
On leave from the Institute of Chemistry, University of the Punjab, Lahore, Pakistan.
See, for example, Bhonsle, J. B.; Clark, T.; Bartolotti, L.; Hicks, R. P. Curr. Topics Med. Chem. 2013, 13, 3205-3224;
Wong, C. F.; Bairy, S. Current Pharm. Design 2013, 19, 4739-4754; Teixeira, C.; Serradji, N.; Amroune, S.; Storck, K.;
Rogez-Kreuz, C.; Clayette, P.; Barbault, F.; Maurel, F. J. Mol. Graphics & Modelling 2013, 44, 91-103; Ghemtio, L.;
Perez-Nueno, V. I.; Leroux, V.; Asses, Y.; Souchet, M.; Mavridis, L.; Maigret, B.; Richie, D. W. Comb. Chem. High
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2002-2012; Perez-Riverol, Y.; Vera, R.; Mazola, Y.; Musacchio, A. Curr. Topics Med. Chem. 2012, 12, 1790-1796. For a
discussion of modern tactics in drug discovery, see Lee, J. A.; Uhlik, M. T.; Moxham, C. M.; Tomandl, D.; Sall, D. J. J.
Med. Chem. 2012, 55, 4527-4538; Gomtsyan, A. Chem. Het. Cmpds. 2012, 48, 7-10. For a discussion of the relevance of
incorporating more 3D shape to potential pharmaceuticals, see Lovering, F.; Bikker, J.; Humblet, C. J. Med. Chem. 2009,
52, 6752-6756.
3.
4.
Yet, L. Comp. Heterocycl. Chem. III, Katritzky, A. R.; Ramsden, C. A.; Scriven, E. F. V.; Taylor, R. J. K. Eds., Elsevier,
Oxford, 2008, 4.01, 1-141 and references therein.
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Schwarz, N.; Beller, M. Org. Lett. 2008, 10, 2377-2379; Giampietro, N. C.; Wolfe, J. P. J. Am. Chem. Soc. 2008, 130,
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Venkataramasubramanian, V.; Sudalai, A. Org. Lett. 2012, 14, 2468-2471; Yamamoto, Y.; New J. Chem. 2013, 37, 3873;
Chand, S. S.; Prakash, P.; Szymoniak, J.; Preethanuj, P.; Dhanya, B. P.; Radhakrishnan, K. V. Org. Lett. 2013, 15, 3338-
3341 and references therein. For a review of pyrazolidine synthesis and applications, see Davis, L. O. Org. Prep. Proced.
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6.
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12.
Dunford, D. G.; Chaudhry, F.; Kariuki, B.; Knight, D. W.; Wheeler, R. C. Tetrahedron Lett. 2012, 53, 7006-7009 and
references therein.
o
o
When temperatures above 45 C were required, dichloroethane, b.p. 84 C, was used. As concentrated sulfuric acid can
only be largely suspended in dichloromethane, measuring ‘standardized’ mixtures was also quite inaccurate.
Typically, 0.5 equivalent of acid was used with respect to the precursor hydrazine. Reactions were carried out in anhydrous
dichloromethane under dry nitrogen. Triflic acid was measured by syringe and added to the solution. Concentrated sulfuric
acid was measured dropwise by glass pipette; typically ~30 mg (two drops) was added to 4 mL of dry dichloromethane.
13.
X-ray analysis of pyrazolidine 24: C14H20N2O4S, Mr=312.38, Triclinic, P-1, a=8.2711(4) Å, b=9.5914(6) Å, c= 10.2058(6)
β
V=767.33(8) Å3, Z=2, DX=1.352 Mg m−3, λ(Mo Kα)=0.71073 Å, μ=0.228
cm−1, F(000)=332, T=160(2) K, crystal size = 0.30 x 0.30 x 0.12 mm3, Reflections collected = 5124, Independent
= 0.0462, Final R1 = 0.0892, wR2 = 0.1832 for I>2sigma(I), and R1 =
int
0.1267, wR2 = 0.199 for all data. The CIF files have been deposit at Cambridge Crystallographic Deposit Center with
registry number CCDC 888756.
In the crystal, the toluene and methyl ester groups adopt a cis conformation. The other face of the phenyl ring overlaps
partly with a ring from a neighbouring molecule resulting in intermolecular   interaction.
14.
X-ray analysis of pyrazolidine 33: C19H28N2O4S, Mr=380.49, Triclinic, P-1, a=8.8933(6) Å, b=10.0576(6) Å,
c=11.9571(5)
β
V=979.36(10) Å3, Z=2, DX=1.290 Mg m−3, λ(Mo
Kα)=0.71073 Å, μ=0.191 cm−1, F(000)=408, T=160(2) K, crystal size = 0.35 x 0.25 x 0.09 mm3, Reflections collected =
= 0.0598, Final R1 = 0.0914, wR2 = 0.1806 for
int
I>2sigma(I), and R1 = 0.1887, wR2 = 0.2244 for all data. The CIF files have been deposit at Cambridge Crystallographic
Deposit Center with registry number CCDC 888757.
The toluenesulfonyl and methyl ester groups adopt a trans conformation in the crystal. Thephenyl ring is involved in  
interactions through partial overlap with a ring from a neighbouring molecule. The closest contact made by the opposite
face of the ring is through the tertiary hydrogen, with an intramolecular C-H...ring-centroid interaction of ca. 2.7 Å.
E-mail: knightdw@cardiff.ac.uk

[Graphical abstract]
A new method for the synthesis of pyrazolidines
Faryal Chaudhry, Benson M. Kariuki and David W. Knight
Protected allylic hydrazines, prepared
c.H2SO4
using Mitsunobu couplings, can be
cyclised efficiently to give good to
excellent yields of pyrazolidines
using strong acid catalysts.
R3
N R1
HN
R2
N
R3
R1
N
R2
Key words: Pyrazolidine; synthesis; acid-catalysed; cyclisation; hydrazines.
E-mail: knightdw@cardiff.ac.uk

Highlights.
The synthesis of substituted pyrazolidines using simple, cost-effective methodology.
Catalysis by sulfuric acid.
Secondary benzylic and secondary carbenium ions can also be trapped.
Short approach to generate precursors.
Regiospecific pathway.