Nitric acid in dichloromethane solution. Facile preparation from potassium nitrate and sulfuric acid

Article abstract of DOI:10.1016/S0040-4039(00)02253-X

Pure dry HNO₃ can be liberated from KNO₃ with 96% H₂SO₄ directly into CH₂Cl₂ to yield solutions of variable concentration for use in a number of organic reactions. The present method efficiently replaces the employment of 100% HNO₃ in some synthetic applications, avoiding the problems associated in storage and handling the acid.

Full text of DOI:10.1016/S0040-4039(00)02253-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 1387–1389
Nitric acid in dichloromethane solution. Facile preparation
from potassium nitrate and sulfuric acid
Paolo Strazzolini,* Angelo G. Giumanini and Antonio Runcio
Department of Chemical Sciences and Technologies, University of Udine, via del Cotonificio 108, I-33100 Udine, Italy
Received 1 November 2000; revised 28 November 2000; accepted 6 December 2000
Abstract—Pure dry HNO can be liberated from KNO with 96% H SO directly into CH Cl to yield solutions of variable
3
3
2
4
2
2
concentration for use in a number of organic reactions. The present method efficiently replaces the employment of 100% HNO3
in some synthetic applications, avoiding the problems associated in storage and handling the acid. © 2001 Elsevier Science Ltd.
All rights reserved.
Commercial 100% HNO3 in CH Cl2 solution has
2
recently proved to be a very useful reagent in organic
synthesis, either in regio-controlled electrophilic aro-
1
matic nitration or in the deprotection of t-butyl esters
2
3
of carboxylic acid and amino acid derivatives. Despite
some reports assessing potential explosion hazards in
4
handling HNO –CH Cl mixtures, we have never expe-
3
2
2
rienced any problem in using such solutions. Neverthe-
less, purchasing, storage and handling of 100% HNO3
may represent difficulties, due to the strong oxidising
Scheme 1.
a
Table 1. Nitration of aromatic substrates by KNO –H SO in CH Cl (Scheme 1)
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2
4
2
2
b
Conversion (%)c
b
Entry
Substrate (1)
React. Time (h)
Product (2)
Isomer Ratio (o-/m-/p-, rel.%)
1
2
3
4
5
PhCH COOMe (1a)
24
1
2
2
24
>99 (97)
>99 (93)
97 (95)
97 (92)
>99 (93)
2a
2a
2b
2c
2d
75/8/17
49/14/37
84/3/13
85/5/10
86/4/10
2
d
PhCH COOMe (1a)
2
e
PhCH CHO (1b)
2
e
PhCH COMe (1c)
2
PhCH COPh (1d)
2
a
Unless otherwise specified, finely powdered KNO3 (50.0 mmol) was treated with the appropriate amount of 96% H SO (47.5 mmol) and the
2
4
mixture stirred for 15 min at room temperature; CH Cl (25.0 mL) was added to the homogeneous slurry so obtained and the mixture cooled
2
2
at 0°C with vigorous stirring. A solution of the substrate 1 (5.0 mmol) in CH Cl2 (8.0 mL) was added dropwise and the stirring continued at
2
room temperature for the required time. The reaction mixture was then poured into 10% aqueous Na SO (30 mL) and the separated organic
2
4
phase washed with 10% aqueous Na SO (2×20 mL), dryed over anhydrous Na SO , concentrated to dryness and the products obtained
2
4
2
4
conveniently purified.1
b
b
c
1b
All substrates and products are commercially available (Aldrich, Milano, Italy) or have been reported elsewhere.
1
Reported conversions were determined by H NMR on intact reaction mixtures, after dilution with CDCl : only mononitration was observed.
3
Isolated yields are in parentheses.
d
e
The reaction was carried out as reported above using: 25.0 mmol KNO –23.8 mmol 96% H SO in 1.5 mL CH Cl and 0.5 mL CH Cl2 to
dissolve the substrate.
After 24 h extensive oxidation took place.
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2
2
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Keywords: deblocking; nitration; nitric acid and derivatives; dichloromethane.
*
Corresponding author. Tel.: +39 0432 558870; fax: +39 0432 558803; e-mail: strazzolini@dstc.uniud.it
0
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)02253-X

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P. Strazzolini et al. / Tetrahedron Letters 42 (2001) 1387–1389
5
nature of the acid. Moreover, its inherent instability,
down. The colourless homogeneous slurry so obtained
was then stirred three times (10 min) with portions of
producing nitrogen oxides and H O on storage, modifies
2
its properties favouring, inter alia, unwanted oxidations
and causes dilution ending up in loss of titre as well as
miscibility with CH Cl . For such reasons, a method
circumventing these drawbacks would be highly desir-
able.
CH Cl2 (1×30 mL and 2×20 mL) and the resulting
2
extracts combined and filtered through a sintered glass
septum and used as such in desired applications. For
analytical purposes, the whole organic solution was
2
2
extracted with H O (3×30 mL) and the combined
2
aqueous phase submitted to the necessary assays (alkali-
metric titration, BaCl2 and KMnO4 tests, ion chro-
matography), after subtraction of suitable blanks. The
CH Cl solution (ca. 70 mL) was found to average 1.19
Consequently, we decided to consider the possibility of
producing a solution of pure HNO in CH Cl , suitable
3
2
2
for any subsequent synthetic purpose, by freeing the
acid with concentrated H SO in situ from some readily
2
2
M HNO (83% recovered yield of the acid) and was free
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4
3
available and cheap nitrate. Nitric acid inorganic salts
are in general very stable chemicals and among them
of H SO , as well as HCl originating by decomposition
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4
2−
−
of the solvent (<30 mg/L SO , <0.3 mg/L Cl ). In
4
KNO is common, cheap, nature friendly and safe to
addition, ion chromatography and a negative KMnO4
test ruled out the presence of nitrogen products of lower
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6
handle. We found that the use of finely powdered
KNO and an equimolecular amount of H SO , to be
oxidation state. When needed, the solution of HNO so
obtained can be concentrated by removal of part of the
solvent by distillation at atmospheric pressure.
3
2
4
3
stirred with the solid (slightly exothermic reaction) for 1
h at rt with protection from light and eventual extrac-
tion of the slurry with three portions of dry solvent,
gave pure CH Cl solutions of HNO with a molarity of
We have tested the solutions so obtained against two
reactions employing HNO in CH Cl (Tables 1 and 2):
2
2
3
ca. 1.2. The efficiency of the process was above 80%, as
could be established alkalimetrically after thorough
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2
2
more conveniently, the substrate could be present
already in the extraction solvent. In order to optimise
the KNO –H SO ratio necessary for the completion of
extraction of the organic phase with H O.
2
3
2
4
As the result of a few preliminary experiments, a typical
preparation involved mixing finely powdered KNO3
the nitration reaction, a set of experiments was per-
formed where the reactants (Table 1, entry 1) were
treated with increasing amounts of H SO . After 24 h at
(
100 mmol, 10.1 g) with concentrated H SO (96%, 98.8
2 4
2
4
mmol, 5.5 mL) with efficient stirring, for 1 h at rt in the
dark with protection from external moisture. Lumps
that form during this process should be carefully broken
rt, the following conversions were observed: KNO3/
H SO4 1.00:0.75 (mol/mol), 70%; 1.00:0.85, 91%;
2
1.00:0.95, >99%.
Scheme 2.
a
Table 2. Nitrolysis of t-butyl esters of carboxylic acids by KNO –H SO in CH Cl (Scheme 2)
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2
4
2
2
b
Conversion (%)c
b
Entry
Substrate (3)
G
Product (4)
Yield (%)
1
2
3
3a
3b
3c
3d
Me C
PhCH2
Ph
>99
>99
>99
98
4a
4b
4c
4d
86
92
93
88
3
d
4
L-ZHN(Me)CH
a
Unless otherwise specified, finely powdered KNO3 (40.0 mmol) was treated with the appropriate amount of 96% H SO (38.0 mmol) and the
2
4
mixture stirred for 15 min at room temperature; CH Cl (10.0 mL) was added to the homogeneous slurry obtained and the mixture cooled at
2
2
0
°C with vigorous stirring. A solution of the substrate 3 (20.0 mmol) in CH Cl (10.0 mL) was added dropwise and the stirring continued at
2 2
0
°C for 2 h. After this time, the reaction mixture was poured into 10% aqueous Na CO (120 mL) and Et O (50.0 mL) was added. The separated
2
3
2
organic phase was discarded and the aqueous phase made acidic with 37% HCl (ca. 3.5 mL), and extracted with Et O (3×30 mL). The combined
2
ethereal phase was washed with 10% aqueous Na SO (1×30 mL), dryed over anhydrous Na SO concentrated to dryness and the product 4
2
4
2
4,
2
,3
obtained conveniently purified.
All substrates and products are commercially available (Aldrich, Milano, Italy) or have been reported elsewhere.
Reported conversions were determined by H NMR on intact reaction mixtures after dilution with CDCl3.
The reaction was carried out as reported above using: 70.0 mmol KNO –66.0 mmol 96% H SO in 10.0 mL CH Cl and 10.0 mL CH Cl2 to
b
c
2,3
1
d
3
2
4
2
2
2
dissolve the substrate.

P. Strazzolini et al. / Tetrahedron Letters 42 (2001) 1387–1389
1389
1
,2
3
Nitration (Scheme 1) and nitrolytic (Scheme 2) reac-
tions were best performed by mixing CH Cl solutions
Dr. P. Martinuzzi for NMR data collection and to Mr.
P. Polese for skilful assistance.
2
2
of the appropriate substrate with a suitable amount of
the preformed KNO –H SO slurry, as reported in
Tables 1 and 2. The results obtained were, in all cases,
coincidental with those afforded by reactions in which
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2
4
References
commercial fuming (d=1.51) HNO was employed in
1. (a) Strazzolini, P.; Verardo, G.; Gorassini, F.; Giumanini,
A. G. Bull. Chem. Soc. Jpn. 1995, 68, 1155–1161; (b)
Strazzolini, P.; Giumanini, A. G.; Runcio, A.; Scuccato,
M. J. Org. Chem. 1998, 63, 952–958.
3
1
–3
CH Cl .
2
2
In conclusion, in view of the peculiar behaviour of
HNO in the aprotic solvent CH Cl , readily available
2. Strazzolini, P.; Dall’Arche, M. G.; Giumanini, A. G.
3
2
2
solutions prepared and described here are expected to
offer further advantages and opportunities with respect
to known reactions of the neat acid, as well as reactions
Tetrahedron Lett. 1998, 39, 9255–9258.
3. Strazzolini, P.; Scuccato, M.; Giumanini, A. G. Tetra-
hedron 2000, 56, 3625–3633.
of the acid at different concentrations in H O or
4. (a) Andrussow, L. Chim. Ind. (Paris) 1961, 86, 542–545
(Chem. Abst. 1963, 58, 12362f); (b) Romanova, L. B.;
Ivanova, M. E.; Nesterenko, D. A.; Eremenko, L. T. Russ.
Chem. Bull. 1994, 43, 1207–1208 (Izv. Akad. Nauk, Ser.
Khim. 1994, 1271–1272; Chem. Abst. 1995, 122, 105214).
2
H SO . Moreover, the reaction producing HNO , being
2
4
3
−
1 7
only slightly exothermic (DH°=−21.1 kJ mol ),
proves suitable for any scale-up purpose.
5. Stern, S. A.; Mullhaupt, J. T.; Kay, W. B. Chem. Rev.
Acknowledgements
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istry, 4th Edn; John Wiley: Chichester, UK, 1980; p. 430.
6
This work was supported in part by grants to A.G.G.
CNR 95.01044CT03, 96.02740CT03, 97.02807CT03)
and to P.S. (MURST 1994, 40%). We are indebted to
7. Calculated from literature standard enthalpy of formation
values. See: CRC-Handbook of Chemistry and Physics,
76th Edn; CRC Press: Boca Raton, FL, USA, 1995.
(
.
.