A safe and efficient route for the preparation of nitro-, dinitro-, and trinitrophenyl chloroformates

Article abstract of DOI:10.1080/00397911.2012.709300

A safe and simple method has been developed for synthesis of chloroformates derived from 2-nitrophenol, 4-nitrophenol, 2,4-dinitrophenol, 2,4,6-trinitrophenol, and pentafluorophenol, the yields being in the range of 72-96%. The method is based on a heterogeneous reaction of the substituted phenol with phosgene dissolved in dichloromethane catalyzed with solid anhydrous potassium carbonate. The synthesis of 2,4,6-trinitrophenyl chloroformate takes place only in the presence of a phase-transfer catalyst, in this case the easily recovered α,ω-dimethoxy poly(ethylene glycol) (PEG; M = 2kDa). The only waste products of the suggested synthesis of the mentioned esters are sodium chloride and potassium chloride. The method markedly reduces the explosion risk connected with drying and handling of salts of mono-, di-, and trinitrophenols and is much more environmentally friendly than the currently used methods. Copyright

Full text of DOI:10.1080/00397911.2012.709300

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A Safe and Efficient Route for the
Preparation of Nitro-, Dinitro-, and
Trinitrophenyl Chloroformates
Miloš Sedlák a , Vladimír Pejchal a , Aleš Imramovský a & Jiří
Hanusek a
a Institute of Organic Chemistry and Technology , Faculty of
Chemical Technology, University of Pardubice , Pardubice , Czech
Republic
Accepted author version posted online: 20 Mar 2013.Published
online: 03 Jun 2013.
To cite this article: Miloš Sedlák , Vladimír Pejchal , Aleš Imramovský & Jiří Hanusek (2013): A
Safe and Efficient Route for the Preparation of Nitro-, Dinitro-, and Trinitrophenyl Chloroformates,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 43:17, 2365-2369
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Synthetic Communications1, 43: 2365–2369, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2012.709300
A SAFE AND EFFICIENT ROUTE FOR THE
PREPARATION OF NITRO-, DINITRO-, AND
TRINITROPHENYL CHLOROFORMATES
ꢀ
´
Milos Sedlak, Vladimır Pejchal, Ales Imramovsky, and
Jirı Hanusek
´
ꢀ
´
ˇ
´
Institute of Organic Chemistry and Technology, Faculty of Chemical
Technology, University of Pardubice, Pardubice, Czech Republic
GRAPHICAL ABSTRACT
Abstract A safe and simple method has been developed for synthesis of chloroformates
derived from 2-nitrophenol, 4-nitrophenol, 2,4-dinitrophenol, 2,4,6-trinitrophenol, and pen-
tafluorophenol, the yields being in the range of 72–96%. The method is based on a hetero-
geneous reaction of the substituted phenol with phosgene dissolved in dichloromethane
catalyzed with solid anhydrous potassium carbonate. The synthesis of 2,4,6-trinitrophenyl
chloroformate takes place only in the presence of a phase-transfer catalyst, in this case
the easily recovered a,x-dimethoxy poly(ethylene glycol) (PEG; M ¼ 2 kDa). The only
waste products of the suggested synthesis of the mentioned esters are sodium chloride
and potassium chloride. The method markedly reduces the explosion risk connected with
drying and handling of salts of mono-, di-, and trinitrophenols and is much more
environmentally friendly than the currently used methods.
Supplemental materials are available for this article. Go to the publisher’s online edition
of Synthetic Communications1 to view the free supplemental file.
Keywords Acylation; phase-transfer catalysis; poly(ethylene glycol)
INTRODUCTION
One group of the currently manufactured specialties of phosgene chemistry are
mono-, di-, and trinitrophenyl chloroformates.[1] These esters containing good
leaving groups are particularly used for activation of amino and hydroxy groups
in syntheses[1] of the carbonates, carbamates, and ureas that find applications in
Received May 25, 2012.
Address correspondence to Milos Sedlak, Institute of Organic Chemistry and Technology, Faculty
ꢀ
of Chemical Technology, University of Pardubice, Studentska 573, 532 10 Pardubice, Czech Republic.
´
´
E-mail: Milos.Sedlak@upce.cz
2365

´
M. SEDLAK ET AL.
2366
agrochemistry,[2] medicinal chemistry,[3–5] or nanochemistry.[6] In contrast to the
syntheses of chloroformates derived from alcohols possessing sufficiently nucleophi-
lic oxygen atoms, the syntheses of chloroformates derived from acidic phenols
(pKa < 10) necessitate transformation of these little reactive hydroxy compounds
into the corresponding salts (phenolates), which are subsequently acylated with
phosgene. Most often, the syntheses start from sodium salts of 2-nitrophenol,[7]
4-nitrophenol,[8] and 2,4-dinitrophenol.[9] In the case of 2,4,6-trinitrophenol (picric
acid), the synthesis requires application of the silver salt (silver picrate).[10] The men-
tioned salts are explosive compounds, and in particular the silver picrate possesses
properties of high explosives.[11,12] According to the currently used technological
methods[1] it is necessary to prepare the corresponding dry nitrophenolate. The dry-
ing is conducted in a vacuum drying cabinet at the lowest temperature possible.
Another drying method is azeotropic dehydration of a wet suspension of the corre-
sponding salt (e.g., with toluene).[1] Then the solid anhydrous nitrophenolate or its
suspension in solvent is gradually added to the solution of phosgene in the respective
solvent. After the reaction is finished, the next operation is distilling off a part of
solvent with excess phosgene, followed by filtration removal of the corresponding
chlorides and final distillation or concentrating the filtrate for precipitation of the
product. The described procedure is not only highly energy consuming but also
connected with hygienically objectionable handling the salts of the mono-, di-, and
trinitrophenols and with high hazard of explosion. Other described methods[13] for
the preparation of chloroformates consist of reactions of nitrophenols with phosgene
in homogeneous medium in the presence of dissolved organic bases,[13] such as
dimethylaniline, pyridine, triethylamine, or diisopropylethylamine. The drawbacks
of these synthetic methods are the relatively high price of the amines and the frequent
formation of undesirable colored side products that contaminate the final product.
The technological and ecological problems connected with the application of
organic bases follow from the necessity of subsequent removal or recovery of the
hydrochlorides of the amines.[13]
RESULTS AND DISCUSSION
The preparation of the chloroformates of 2-nitrophenol, 4-nitrophenol,
2,4-dinitrophenol, and pentafluorophenol was performed by means of a new, safe,
and ecologically acceptable method. This synthetic approach is based on the follow-
ing procedure: Solid anhydrous potassium carbonate is added gradually to the sol-
ution of corresponding phenol with dissolved excess phosgene under stirring. The
reaction stoichiometry was optimized by using 2 mol of phosgene and 1 mol of pot-
assium carbonate per 1 mol of the starting phenol; the only side products are potass-
ium chloride, carbon dioxide, and hydrogen chloride. During the reaction, the
corresponding phenolate anion is formed on the surface of potassium carbonate par-
ticles, and this anion reacts with the dissolved phosgene to give the respective chlor-
oformate. The potassium carbonate is converted into potassium chloride, and the
chloroformate produced is washed off the carbonate surface by dichloromethane,
which enables further formation of phenolate and continuation of the reaction.
The surface of potassium carbonate is continuously restored by the evolving carbon
dioxide. The reaction is accompanied by only mild foaming. In contrast to that, the

NITROPHENYL CHLOROFORMATES
2367
Scheme 1. Synthesis of substituded phenyl chloroformates.
reaction of potassium carbonate (alone, in the absence of phenolate) with phosgene
in dichloromethane proceeds very violently. The whole process is relatively short:
The starting substituted phenol is completely consumed within 1 h. In the case of
nitrophenols, the end of reaction is indicated quite clearly by decolorization of the
surface of inorganic heterogeneous phase. Final operation is distilling off the solvent
containing carbon dioxide, hydrogen chloride and traces of phosgene, which is quan-
titatively absorbed in a spray column with 15% aqueous NaOH solution. After cool-
ing, the suspension is filtered to remove potassium chloride. The filtrate containing
the respective chloroformate is concentrated for crystallization or distilled in vacuum
after removal of dichloromethane by evaporation. In the experiments performed, the
starting phenols underwent complete conversion, and practical yields of nitro- and
dinitrophenyl chloroformates were in the range of 72–96% (Scheme 1).
This method can also be applied to syntheses of other chloroformates derived
from other acidic phenols, which was proved in the synthesis of pentafluorophenyl
chlorformate (yield 85%).[14]
However, in an attempt at synthesis of 2,4,6-trinitrophenyl chloroformate,[10]
the acylation under these conditions does not proceed, not even after 4 days. The
reaction of picric acid with phosgene took place only after addition of a
phase-transfer catalyst (10 mol%). The catalyst chosen in this case was a,x-
dimethoxy poly(ethylene glycol) (PEG, M ¼ 2 kDa), which works similarly as crown
ethers and, in addition is much cheaper and can be recovered thanks to its insolu-
bility in diethyl ether.[15,16] In the case of this acylation, complete conversion was
achieved after 3 days. After removal of carbon dioxide, hydrogen chloride and traces
of phosgene and potassium chloride were filtered off. After removal of dichloro-
methane by distillation, the residue contained PEG and the product. The product
was separated by extraction of the distillation residue with diethyl ether; the extract
was concentrated and the product crystallized in the yield of 83%. The composition
and chemical structure of 2,4,6-trinitrophenyl chloroformate was verified by micro-
analysis and NMR (see Supplementary Material, available online). The PEG preci-
pitated with diethyl ether was reused in the next three experiments without any
statistically significant decrease in the yield of product.
EXPERIMENTAL
A solution of phosgene (9.9 g, 0.10 mol) and corresponding phenol (0.05 mol)
in dichloromethane (400 g) was treated with anhydrous potassium carbonate
(5.3 g, 0.05 mol) added at 25 ꢀC within 5 min. The mixture was intensively stirred
without cooling. In the case of nitrophenols, the surface of potassium carbonate

´
M. SEDLAK ET AL.
2368
became yellow, and the surface of the solid phase then decolorized within ca. 45 min.
The mixture was stirred for another ca. 30 min. Dichloromethane (100 mL) was dis-
tilled off, and the solid portion (ca. 4 g) was obtained from the cooled distillation
residue by filtration. The filtrate was rid of all dichloromethane by distillation on
a water bath, and the product was purified by distillation or crystallization.
2-Nitrophenyl Chloroformate
Yield 86%, 131–133 ꢀC=7 mm (131.5–132.5 ꢀC=7 mm[7]) in the form of yellowish
liquid (8.6 g, 1H NMR (400.13 MHz, CDCl3): d 8.16 (1H, dd, J ¼ 8.2 Hz, J ¼ 1.6 Hz,
H3), 7.74 (1H, dt, J ¼ 8.2 Hz, J ¼ 1.6 Hz, H4), 7.52 (1H, dt, J ¼ 8.2 Hz, J ¼ 1.3 Hz,
H5), 7.38 (1H, dd, J ¼ 8.2 Hz, J ¼ 1.3 Hz, H6). 13C NMR (100.62 MHz, CDCl3): d
154.9, 149.1, 143.8, 135.5, 128.3, 126.1, 124.2.
4-Nitrophenyl Chloroformate
1
Yield 92%, mp 78–80 ꢀC (81–82 ꢀC[8]). H NMR (400.13 MHz, CDCl3): d 8.30
(2H, d, J ¼ 9.1 Hz, H3, H5), 7.42 (2H d, J ¼ 9.1 Hz, H2, H6). 13C NMR
(100.62 MHz, CDCl3): d 155.1, 148.8, 146.3, 125.6, 121.6.
2,4-Dinitrophenyl Chloroformate
1
Yield 72%, mp 57–59 ꢀC (57.4 ꢀC[9]). H NMR (400.13 MHz, CDCl3): d 9.01
(1H, d, J ¼ 2.8 Hz, H3), 8.58 (1H, dd, J ¼ 9.0 Hz, J ¼ 2.6 Hz, H5), 7.63 (1H, d,
J ¼ 9.2 Hz, H6). 13C NMR (100.62 MHz, CDCl3): d 148.4, 147.3, 145.9, 145.7,
129.9, 126.2, 121.9.
Pentafluorophenyl Chloroformate
Yield 85%, bp 68–70 ꢀC=20 mm (53 ꢀC=13 mm[14]) in the form of colorless
liquid (10.5 g, 85%). 13C NMR (100.62 MHz, CDCl3): d 148.6 (s), 142.0 (m), 139.2
(m), 136.6 (m), 130.9 (m). 19F NMR (376.46 MHz, CDCl3): d ꢁ 152.4 (2 F, d,
J ¼ 16.9 Hz); ꢁ155.3 (1 F, t, J ¼ 21.5 Hz); ꢁ 161.2 (2 F, t, J ¼ 19.6 Hz).
2,4,6-Trinitrophenyl Chloroformate
1
Yield 83%, mp 78–80 ꢀC (77.3 ꢀC[10]). H NMR (400.13 MHz, CDCl3): d 8.84
(3H, s). 13C NMR (100.62 MHz, CDCl3): d 144.6, 145.7, 127.2, 122.9. Anal. calcd.
for C7H2ClN3O8 (290.95): 28.84% C; 0.69% H; 12.16% Cl; 14.41% N. Found:
28.91% C; 0.71% H; 12.24% Cl; 14.38% N.
CONCLUSION
The described method of synthesis of 2-nitrophenyl chloroformate, 4-nitrophe-
nyl chloroformate, 2,4-dinitrophenyl chloroformate, 2,4,6-trinitrophenyl chlorofor-
mate, and pentafluorophenyl chloroformate did not require the application of
separately prepared phenolate salts[7–9] and application of organic bases.[1,13] This

NITROPHENYL CHLOROFORMATES
2369
method fundamentally simplifies the earlier laboratory and industrial procedures; in
particular, it eliminates the explosion risk connected with handling the starting salts
of (mono-, di-, tri-)nitrophenols, especially silver picrate.[10] The respective pheno-
lates are formed directly in the reaction mixture on the surface of potassium carbon-
ate, where they undergo subsequent reaction with phosgene. The synthesis can be
conducted in a simple way and also on industrial scale in a single reactor. In com-
parison with the industrial technologies currently used,[1,7–9,13] this method is dis-
tinctly more environmentally friendly, with its only waste product being sodium
chloride or potassium chloride.
ACKNOWLEDGMENT
The authors acknowledge financial support from the University of Pardubice
and the project GACR P 106=11=005.
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