3,5-Dimethylpyrazolium fluorochromate(VI), C5H8N2H[CrO3F], (DmpzHFC): A convenient new reagent for oxidation of organic substrates

Article abstract of DOI:10.1016/S0040-4020(01)00116-8

A new chromium(VI) reagent, 3,5-dimethylpyrazolium fluorochromate, C₅H₈N₂H[CrO₃F] (DmpzHFC), has been developed by reacting dmpz with CrO₃ and aqueous HF for the selective oxidation of primary, secondary and allylic alcohols to the corresponding carbonyl compounds, polycyclic hydrocarbons to cyclic ketones and allylic Δ⁵-steroids to the corresponding α,β-unsaturated ketones.

Full text of DOI:10.1016/S0040-4020(01)00116-8

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 2445±2448
3,5-Dimethylpyrazolium ¯uorochromate(VI),
C5H8N2H[CrO3F], (DmpzHFC): a convenient new
reagent for oxidation of organic substrates
Upasana Bora,a Mihir K. Chaudhuri,a,p Deepa Dey,a Dipak Kalita,a Wancydora Kharmawphlangb
and Gagan C. Mandalb
aDepartment of Chemistry, Indian Institute of Technology, Guwahati 781031, India
bDepartment of Chemistry, North Eastern Hill University, Shillong 793022, India
Received 16 June 2000; revised 3 January 2001; accepted 18 January 2001
AbstractÐA new chromium(VI) reagent, 3,5-dimethylpyrazolium ¯uorochromate, C5H8N2H[CrO3F] (DmpzHFC), has been developed
by reacting dmpz with CrO3 and aqueous HF for the selective oxidation of primary, secondary and allylic alcohols to the corresponding
carbonyl compounds, polycyclic hydrocarbons to cyclic ketones and allylic D5-steroids to the corresponding a,b-unsaturated ketones.
q 2001 Elsevier Science Ltd. All rights reserved.
Over recent years, chromium(VI) based oxidising agents
have been extensively worked on leading to the develop-
ment of a good number of reagents, some of which have
become quite popular and performing well as oxidising
agents. Some of the important entries in the list of reagents
are the Collins reagent,1 chromium trioxide-3,5-dimethyl-
pyrazole complex,2 pyridinium chlorochromate (PCC),3
pyridinium dichromate (PDC)4 and 2,20-bipyridinium
chlorochromate (BiPCC).5 Over several years our group
has been involved in developing newer reagents and
methodologies6 allowing oxidations to be performed under
mild conditions. The versatility of pyridinium ¯uoro-
chromate (PFC)6a,6b,6c,7 goes well to prove the point.
However, the chromium based reagents that have been
developed so far have some limitations that cannot be over-
looked. These include the inherent problems of acidity of
the reagents and their limited solubility in organic solvents.
As a consequence of the aforementioned problems, these
reagents have proved to be unsuitable for oxidations on
several occasions. Consequently, the search for a pre-
eminent new reagent persisted which has now led to the
synthesis of 3,5-dimethylpyrazolium ¯uorochromate(VI),
C5H8N2H[CrO3F] (DmpzHFC).
hydro¯uoric acid and 3,5-dimethylpyrazole in the molar
ratio of 1:2:1. The compound analysed very well. It is
soluble in dichloromethane and highly soluble in aceto-
nitrile, chloroform, ethanol, methanol and acetone. The
solubility of DmpzHFC is comparatively higher than PFC,
PCC and PDC. The reagent is diamagnetic, EPR silent
and melts at 568C. It is a 1:1 electrolyte (LMˆ
107 V21 cm2 mol21, in CH3CN), showing a pH value of
4.9 (0.01 M aqueous solution) and pKa 7.8. The pH of
0.01 M solutions of PCC, PFC and quinolinium ¯uorochro-
mate (QFC) were found to be 1.75, 2.45 and 3.35, respect-
ively, with the corresponding pKa values being 1.4, 2.7 and
4.7.6d A higher pH value of DmpzHFC compared to its
companion reagents attests to its far less acidic character.
In order to ascertain the ef®cacy of the reagent as an oxidant,
it has been tested on a wide array of substrates. DmpzHFC
readily oxidises primary (entry 1±4, Table 1) and secondary
alcohols (entry 5±9, Table 1) in dichloromethane (Scheme
1) to their corresponding aldehydes and ketones. Similar
oxidations can be performed in acetonitrile without com-
promising the yield of the products.
Fused ring hydrocarbons such as anthracene (entry 10,
Table 1) and phenanthrene (entry 12, Table 1) are oxidised
to 9,10-anthraquinone and phenanthrene-9,10-quinone,
respectively. These oxidations can be performed not only
in dichloromethane but also in acetonitrile or acetic acid.
Importantly, the reagent is found to be quite effective for the
oxidation of D5-steroid systems, (entry 13±15, Table 1)
(Scheme 2) to the corresponding a,b-unsaturated ketones.
In all these cases the products were obtained in moderate to
The reagent 3,5-dimethylpyrazolium ¯uorochromate(VI),
C5H8N2H[CrO3F], (DmpzHFC), can be easily prepared in
excellent yield from the reaction of CrO3 with aqueous
Keywords: alcohols; polycyclic hydrocarbons; D5-steroids; chromium(VI);
oxidations.
p
Corresponding author. Tel.: 191-361-690769; fax: 191-361-690762;
e-mail: mkc@iitg.ernet.in
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(01)00116-8

2446
U. Bora et al. / Tetrahedron 57 (2001) 2445±2448
Table 1. Oxidation of organic substrates with DmpzHFC
Entry
Substrates
Solvent/time (h)
Substrate:oxidant
Producta
Yield (%)b
1.
2.
3.
4.
5.
6.
7.
8.
1-Butanol
CH2Cl2/1.5
CH2Cl2/0.5
CH2Cl2/1
CH2Cl2/1.5
CH2Cl2/0.5
CH2Cl2/1.5
CH2Cl2/2
1:1.1
1:1.25
1:1.25
1:1.5
1:1.25
1:1.1
1:2.5
1:1
1:1.25
1:2.5
1:2
1:2.5
1:6
1:6
1-Butanal
Benzaldehyde
Citronellal
Geranial
Cyclohexanone
Acrolein
Menthone
Glyceraldehyde
Benzil
9,10-Anthraquinone
9,10-Anthraquinone
Phenanthrene-9,10-quinone
3-Acetoxy-7-keto-cholesterol
3-Benzoyloxy-7-keto-cholesterol
7-Keto-pregnonalone acetate
6-Methoxy-1-tetralone
Triphenylphosphine oxide
1a
2a
3a
4a
5a
6a
7a
8a
80
78
70
95
70
95
65
35
70
58
90
70
75
70
60
60
70
Benzyl alcohol
Citronellol
Geraniol
Cyclohexanol
2-Propen-1-ol
Menthol
Glycerol
Benzoin
Anthracene
Anthrone
Phenanthrene
3-Acetoxy cholesterol
3-Benzoyloxy cholesterol
Pregnonalone acetate
6-Methoxy tetralene
Triphenylphosphine
CH2Cl2/1
9.
CH2Cl2/1.5
CH2Cl2/3.5
CH3CN/3
9a
10.
11.
12.
13.
14.
15.
16.
17.
10a
11a
12a
13a
14a
15a
16a
17a
CH2Cl2/4
CH3CN/10
CH3CN/10
CH3CN/12
CH3CN/10
CH2Cl2/2 min
1:6
1:6
1:1.1
a
Products were characterised by comparison with authentic samples (NMR, IR and mass spectra, TLC and mp/bp measurements).
Isolated yields are reported.
b
high yields (Table 1). Notably, D5-steroids are more than
also that the reaction time is much longer (typically ca. 30 h)
compared to the present protocol. It has been now demon-
strated through entries 13±15 (Table 1) that a six molar
equivalent of DmpzHFC in dry acetonitrile afforded the
desired products in good yields in a comparatively much
shorter time (10 h). Notably, D5-steroidal oxidations invol-
ving one of our previously developed reagents,
C5H5NH[CrO3]F (PFC), has not provided very promising
results so far.
mere probes for oxidation as D5-steroids with a ketone func-
tion at C-7 (D5-7-ketones) are found in animal tissues8 and
food stuffs9 and are known to be inhibitors of mammalian
sterol biosynthesis10±12 and cell replication.13,14 Though
such oxidations are not unprecedented in the literature, the
allylic oxidation of D5-systems carried out with chromic
acid reagents,15 PCC,16 PDC17 and RuCl3-TBHP18 has
only a limited success, has involved prohibit ably expensive
reagent or has required a large excess of the reagent (1:25±
120, substrate:oxidant), stringent reaction conditions and a
longer reaction time. Thus, for instance, an amount of 25±
30 molar equivalents of PCC in re¯uxing dichloromethane
required 48 h to afford ca. 55% yield of the product.16 Like-
wise, a reaction time of 24 h was reported to be needed for
similar oxidations involving 25 molar equivalents of PCC or
PDC in re¯uxing benzene or in dimethylsulfoxide or pyri-
dine at 1008C.17 In so far as RuCl3-TBHP oxidations of
D5-steroids are concerned, it is not only that the reagent is
expensive with the oxidation procedure being tedious but
In yet another example, 6-methoxy tetralene (c.f. activated
hydrocarbon; entry 16, Table 1) was oxidised to 6-methoxy-
1-tetralone as a case of ketone formation at the C-1 position.
Incidentally, this product appears to be the key building
block for several life saving drugs and steroid molecules.19
Here again, the reaction time in our case was relatively short
(10 h) with the molar equivalent of the oxidant required
being far less (6 equiv.) compared to literature procedures
(13±48 h, 60±120 equiv.).16,20 In addition, a very facile
oxidation of triphenylphosphine to triphenylphosphine
oxide (entry 17, Table 1) suggests that DmpzHFC is also
capable of acting as an ef®cient oxo-transfer reagent.
A brown microcrystalline product isolated after the oxi-
dation, as the reduced product, has been identi®ed to be a
chromium(IV) species, C5H8N2H[CrO2F], as ascertained
from the results of chemical analyses, chemical determin-
ation of oxidation level of the metal (3.9±4.1), magnetic
Scheme 1.
Scheme 2.

U. Bora et al. / Tetrahedron 57 (2001) 2445±2448
2447
susceptibility ꢀmeff ˆ 2:92 BM at rt) and EPR (single line at
g ˆ 1:935 ^ 0:005† measurements in addition to IR spec-
troscopy. This suggests very clearly that DmpzHFC serves
as a 2-electron-transfer reagent.
added a solution of geraniol (1.02 g, 6.6 mmol) in 10 mL
of CH2Cl2 in one portion. Stirring was continued for 30 min
to give a yellow solution. The progress of the reaction was
monitored by TLC. After completion of the reaction, 50 mL
of dry diethyl ether was added to the reaction mixture and
the whole mass was shaken well, the organic layer decanted
and the residue washed with dry diethyl ether ꢀ3 £ 20 mL†:
The combined organic layers were passed through a short
pad of Celitew, to trap the reduced chromium, and washed
thoroughly with diethyl ether. The combined ®ltrate was
evaporated in a rotavapor under reduced pressure to give a
crude, gummy material which was subjected to column
chromatography over a short pad of silica gel using ethyl
acetate±hexane (1:9) as an eluent to afford geranial (4a,
Table 1) as a colourless liquid. Yield was 1 g (95%), bp
2288C (lit.21a bp 2298C).
To sum up, the easily prepared new reagent (DmpzHFC) has
a number of advantages over its companion reagents like
PCC, PDC and PFC, or RuCl3-TBHP as evident from the
consideration of the amount of the reagent required for a
large variety of oxidations, solubility in different solvents,
controlled acidity, shorter reaction time and high to very
high yields of products. The reduced chromium species
can be trapped on a silica gel or a Celitew column for safe
disposal. Based on all the results hitherto obtained it may be
stated that DmpzHFC is an important addition to the realm
of oxidising agents.
1.2.2. Oxidation of glycerol. An amount of 1.08 g (5 mmol)
DmpzHFC was dissolved in 10 mL of CH2Cl2. To it was
added a solution of glycerol (0.36 mL, 5 mmol) in 10 mL of
CH2Cl2, and the whole was stirred for 1 h. The progress
of the reaction was monitored by GC. An amount of
50 mL of diethyl ether was added to the reaction mixture
and the whole mass was shaken well, the organic layer
decanted and the residue washed with diethyl ether ꢀ3 £
20 mL†: The combined organic layer was concentrated in
a rotavapor and then passed through a short pad of silica gel
to trap the reduced product of the reagent, and washed
repeatedly with diethyl ether. The ®ltrate was evaporated
in a rotavapor to give a crude material which was subjected
to column chromatography over a pad of silica gel using
ethyl acetate±hexane (9:1) as eluent to afford glyceralde-
hyde as dl-mixture. Yield was 0.16 g (35%), mp 1438C
(lit.21b mp 144±1458C).
1. Experimental
1.1. General
IR spectra were recorded using a Perkin Elmer Model No
983 spectrophotometer. H NMR spectra were recorded
1
using 300 MHz Bruker AC-F instrument, GC mass spectra
were recorded in Fission 8000 series using capillary column.
Elemental analyses were performed using Perkin Elmer C,
H, N analyser. ESR spectra were recorded at ambient
temperature by
a Varian E-109 ESR spectrometer
(X-band) with 100 kHz ®eld modulation. Magnetic suscept-
ibility measurements were conducted by the Gouy method
using Hg[Co(NCS)4] as calibrant.
1.1.1. Preparation of 3,5-dimethylpyrazolium ¯uoro-
chromate, DmpzHFC, C5H8N2H[CrO3F]. To a solution
of 5.6 g (56 mmol) CrO3 in 2.5 mL water in a 100 mL poly-
ethylene beaker, 5 mL (120 mmol) 48% HF was added with
stirring. An orange red solution was obtained. The reaction
mixture was then cooled in an ice-bath (temperature,
0±58C) and 5.6 g (58.33 mmol) 3,5-dimethylpyrazole was
added portion-wise, with stirring, when an orange crystal-
line compound separated out. This was ®ltered under
vacuum, using a polyethylene funnel, washed with petro-
leum ether ꢀ3 £ 10 mL†; rapidly dried in a vacuum desic-
cator and ®nally stored in a sealed polyethylene bag in a
freezer. The yield of C5H8N2H[CrO3F] was found to be
11.6 g (92%). The melting point of the compound was
found to be 568C. Electrical conductance (in CH3CN) was
107 V21 cm2 mol21, IR n(KBr): 954(s, Cr±O), 921(s,
Cr±O) and 633(m, Cr±F), 800±1600 cm21 (originating
due to the 3,5-dimethylpyrazolium cation). Electronic
1.2.3. Oxidation of anthracene. In a dry round-bottomed
¯ask, 0.18 g (1 mmol) of anthracene was dissolved in 10 mL
of CH2Cl2. To the solution, 0.54 g (2.5 mmol) of DmpzHFC
was added and re¯uxed for 3.5 h. The progress of the reac-
tion was monitored by TLC. The reaction mixture was
concentrated using a rotavapor and then washed with
50 mL of diethyl ether. The combined organic layer was
passed through a short pad of Celitew to trap the reduced
product of the reagent and washed thoroughly with diethyl
ether. The ®ltrate was evaporated in a rotavapor to give a
crude product which was puri®ed by column chroma-
tography over a short pad of silica gel using ethylacetate±
hexane (1:9) as eluent. 9,10-Anthraquinone was obtained as
a yellow crystalline compound having mp 2718C (lit.22 mp
2738C). Yield of the compound was 0.12 g (58%).
absorption at 27,701 cm21, corresponded to A1! E ꢀe ˆ
1
1
1.2.4. Oxidation of triphenylphosphine. The oxidation
was conducted under nitrogen atmosphere. In a 100 mL
round-bottomed ¯ask was placed 1.81 g (8.39 mmol) of
DmpzHFC and 4 mL of CH2Cl2. PPh3 (2.4 g, 9.16 mmol)
dissolved in 3 mL of CH2Cl2 was added in one portion
maintaining the substrate: oxidant mol ratio of 1:1.1. An
instantaneous exothermic reaction set in and the oxidation
was complete in 2 min. The reaction solution was separated
by centrifugation and then ®ltered through a short silica gel
column. The column material was washed thoroughly with
diethyl ether and ®ltered. The combined ®ltrate and wash-
ings were evaporated on a steam-bath and the white highly
1641 M21 cm21†; 36,765 cm21 to 1A1! A1 ꢀe ˆ
1
1
4101 M21 cm21
†
and 46,296 cm21 to 1A1! E ꢀe ˆ
9706 M21 cm21†: Analysis: found Cr, 24.35%; F, 8.95%;
C, 27.80%; N, 12.98%; H, 3.91%. C5H8N2H[CrO3F] calcu-
lated: Cr, 24.06%; F, 8.80%; C, 27.78%; N, 12.96%; H,
4.21%.
1.2. General procedure for the oxidation of alcohols
1.2.1. Oxidation of geraniol. To a stirred solution of
DmpzHFC (1.57 g, 7.26 mmol) in 10 mL of CH2Cl2 was

2448
U. Bora et al. / Tetrahedron 57 (2001) 2445±2448
Tetrahedron 1987, 43, 5389. (c) Bhattacherjee, M. N.;
Chaudhuri, M. K. Inorg. Synth. 1990, 27, 310. (d) Chaudhuri,
M. K.; Chettri, S. K.; Lyndem, S.; Paul, P. C.; Srinivas, P.
Bull. Chem. Soc. Jpn 1994, 67, 1894. (e) Chaudhuri, M. K.;
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Lakshmiprabha, T. R.; Mandal, G. C. Tetrahedron Lett.
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crystalline product thus obtained was ascertained to be
OPPh3.6b,6d Yield of OPPh3 was 1.78 g (70%).
The products were all characterised by NMR, IR and mass
spectral measurements, mp/bp recording and by comparison
with authentic samples.
1.2.5. Oxidation of D5-steroids: a typical procedure.
Cholesterol acetate (entry 13, Table 1) (0.43 g, 1 mmol)
was dissolved in anhydrous CH3CN (10 mL) containing
7. (a) Nonaka, T.; Kanemoto, S.; Oshima, K.; Nozaki, H. Bull.
Chem. Soc. Jpn 1984, 57, 2019. (b) Banerji, K. K. J. Chem.
Soc., Perkin Trans. 2 1988, 547. (c) Banerji, K. K. J. Org.
Chem. 1988, 53, 2154. (d) Agarwal, S.; Chowdhury, K.;
Banerji, K. K. J. Org. Chem. 1991, 56, 5111. (e) Moondra,
A.; Mathur, A.; Banerji, K. K. J. Chem. Soc. Dalton Trans.
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Ê
molecular sieves (0.02 g, type 3 A). DmpzHFC (1.3 g,
6 mmol) was added to the substrate and the mixture stirred
under re¯ux for 10 h. The progress of the reaction was
monitored by TLC. Diethyl ether (50 mL) was then added
to the reaction mixture, the ether layer decanted and the
residue further washed with ether ꢀ3 £ 30 mL†: The
combined ether layers were passed through a short pad of
Celitew to trap the reduced chromium. The ethereal solution
was evaporated and the crude material subjected to column
chromatography over silica gel using ethyl acetate±hexane
(1:20) to afford 13a (Table 1) in 0.3 g (75%) yield as a white
crystalline compound having mp 155±1568C (lit.23 mp
157±1598C). [Analysis: found C, 78.61%; H, 10.22%; O,
10.78%. C29H46O3 calculated C, 78.68%; H, 10.49%; O,
8. Parish, E. J.; Nanduri, V. B. B.; Kohl, H. H.; Taylor, F. R.
Lipids 1986, 21, 27 (see also references cited therein).
9. Smith, L. L. Cholesterol Autoxidation, Plenum: New York,
1981.
10. Schroepfer, Jr., G. C. Ann. Rev. Biochem. 1981, 51, 585.
11. Taylor, F. R.; Saucier, S. E.; Shown, E. P.; Parish, E. J.;
Kandutsch, A. A. J. Biol. Chem. 1984, 259, 12382.
12. Sato, Y.; Sonoda, Y.; Morisaki, M.; Ikekawa, H. Chem.
Pharm. Bull. Jpn 1984, 32, 3305.
;
10.84%]. IR, n (KBr): 1741, 1671 cm21 1H NMR
(300 MHz, CDCl3) dH ˆ 5:7 (s, 1H, ±CO±CHv); 4.68
(m, 1H, ±CHOAc); 2.05 (s, 3H, ±OCOCH3); 1.2 (s, 3H,
±CH3); 0.95 (s, 3H, ±CH3); 0.9 (s, 3H, ±CH3); 0.88 (s,
3H, ±CH3); 0.78 ppm (s, 3H, ±CH3).
13. Cheng, K.-P.; Nagano, N.; Bang, L.; Ourisson, G. J. J. Chem.
Res. 1977, (S) 217, (M) 2501.
14. Nagano, H.; Poyser, J. P.; Cheng, K.-P.; Bang, L.; Ourisson,
G. J. J. Chem. Res. 1977, (S) 218, (M) 2522.
15. Salmond, W. G.; Batra, M. A.; Havens, J. L. J. Org. Chem.
1978, 43, 2057 (see also references cited therein).
16. Parish, E. J.; Chitrakorn, S.; Wei, T-Yi Synth. Commun. 1986,
16, 1371.
Acknowledgements
The authors, D. D. and G. C. M. thank CSIR, New Delhi,
and U. B. thanks IITG for award of the research fellowships.
17. Parish, E. J.; Wei, T-Yi Syn. Commun. 1987, 17, 1227.
18. Miller, R. A.; Li, W.; Humphrey, G. R. Tetrahedron Lett.
1996, 37, 3429.
19. (a) Akhrem, A. A.; Titov, Y. A. Total Steroid Synthesis,
Plenum: New York, 1970. (b) Barlaam, B.; Boivin, J.;
Elkaim, L.; Elton-Farr, S.; Zard, S. Z. Tetrahedron 1995, 51,
1675. (c) Fieser, L. F.; Fieser, M. Steroids, Reinhold: New
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