Efficient synthesis of readily water-soluble amides containing sulfonic groups

Article abstract of DOI:10.1080/00397911.2013.794900

A series of various readily water-soluble amides were synthesized by different procedures. These compounds are useful chemical tracers for assessing the cooling progress in a georeservoir during geothermal power plant operation. Acylation of primary amine

Full text of DOI:10.1080/00397911.2013.794900

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Efficient Synthesis of Readily Water-
Soluble Amides Containing Sulfonic
Groups
Krzysztof R. Idzik a , Karsten Nödler a & Tobias Licha a
a Department of Applied Geology , Geoscience Center of the
University of Göttingen , Göttingen , Germany
Accepted author version posted online: 15 Aug 2013.Published
online: 11 Oct 2013.
To cite this article: Krzysztof R. Idzik , Karsten Nödler & Tobias Licha (2014) Efficient Synthesis
of Readily Water-Soluble Amides Containing Sulfonic Groups, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 44:1, 133-140, DOI:
10.1080/00397911.2013.794900
To link to this article: http://dx.doi.org/10.1080/00397911.2013.794900
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Synthetic Communications1, 44: 133–140, 2014
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2013.794900
EFFICIENT SYNTHESIS OF READILY WATER-SOLUBLE
AMIDES CONTAINING SULFONIC GROUPS
¨
Krzysztof R. Idzik, Karsten Nodler, and Tobias Licha
Department of Applied Geology, Geoscience Center of the University of
Go¨ttingen, Go¨ttingen, Germany
GRAPHICAL ABSTRACT
Abstract A series of various readily water-soluble amides were synthesized by different pro-
cedures. These compounds are useful chemical tracers for assessing the cooling progress in a
georeservoir during geothermal power plant operation. Acylation of primary amines was
carried out by basically employing the Schotten–Baumann method. As a second method
a single-phase solvent system consisting of ethyl acetate as an organic solvent and triethy-
lamine as a catalyst was used. Products were characterized by 1H NMR and 13C NMR.
[Supplementary materials are available for this article. Go to the publisher’s online edi-
tion of Synthetic Communications1 for the following free supplemental resource(s): Full
experimental and spectral details.]
Keywords Brine; primary amines; Schotten–Baumann reaction; sulfonic acid amides
Received March 20, 2013.
Address correspondence to Krzysztof R. Idzik or Tobias Licha, Department of Applied Geology,
Geoscience Center of the University of Go¨ttingen, Goldschmidtstrasse 3, 37077 Go¨ttingen, Germany.
E-mail: krzysztof.idzik@pwr.wroc.pl; tobias.licha@geo.uni-goettingen.de
133

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K. R. IDZIK, K. NODLER, AND T. LICHA
134
INTRODUCTION
Compounds susceptible to undergo hydrolysis have raised interest as thermo-
sensitive tracers in geothermal applications.[1,2] Together with their kinetic hydrolysis
parameters it becomes possible to track thermal fronts in geothermal reservoirs and
allows prediction of the thermal drawdown with time. The biggest advantage of these
new tracers is that they are highly water soluble and have no geogenic background
concentrations, and while the amides show no fluorescence at least one of the hydroly-
sis reaction products does. The latter allows performing online measurements under
in situ conditions, further reducing operational costs. While esters react too fast,[3]
amides are sufficient to study high enthalpy systems on longer time scales.[4]
Acylation provides an inexpensive and efficient way for obtaining amides in a
synthetic process.[5] A number of reagents can be used for carrying out this reaction,
such as benzoyl chloride,[6] benzoic anhydride,[7] 2-benzoylthio-1-methylpyridinium
chloride,[8] and benzoyl cyanide.[9]
RESULTS AND DISCUSSION
Acylation of primary amines is carried out in brine solution using a stoichio-
metric amount of acid chloride followed by trituration with aqueous saturated bicar-
bonate solution as the well-known Schotten–Baumann method.[10] The primary
amine is suspended in brine (scale: 1 g of sodium chloride in 3 ml of water) and then
an equivalent amount of acid chloride derivative in acetone (1:1) is added dropwise
under stirring. The desired product is finally obtained by treating the reaction mixture
with saturated bicarbonate solution. To gain insight into the role of the brine, it is
assumed that the high concentration of Clꢀ ions in the reaction mixture prevents a
fast hydrolysis of acid chloride and is also responsible for the slow decomposition
of the tetrahedral intermediate formed by the nucleophilic attack of the amino group
toward the acid chloride. The rationale is supported by the fact that when the reaction
is carried out only in water (instead of brine), the yield is drastically reduced. From
the sodium salt, the required derivatives are obtained by usual acid workup followed
by washing with hot water to remove traces of carboxylic acid. The products are crys-
tallized from methanol–water solution or purified by column chromatography
(Scheme 1).
The main problem in using the Schotten–Baumann method for water-soluble
compounds is the separation of resulting products from salts in the purification step.
Scheme 1. Synthesis of 4-[(naphthalen-1-ylcarbonyl)amino]benzenesulfonic acid (2) obtained by two
different methods.

135

136

137

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K. R. IDZIK, K. NODLER, AND T. LICHA
138
We tried to find an alternative method for obtaining water-soluble amides without
the presence or formation of any inorganic salts. In acetonitrile all reagents were
completely soluble so we used it as a good solvent in the reaction. Triethylamine
was used as a base. Unfortunately, we did not observe any product formation.
Acetonitrile was replaced by ethyl acetate with good results. We noticed that long
reaction times and an insufficient amount of triethylamine can lead to product
decomposion, and in particular in the acidic environment of the reaction resulting
from acid chloride hydrolysis. The best yield was obtained after reaction times of
12 h with excess of triethylamine. By applying this method it is possible to obtain
products free from inorganic salts (Scheme 1). The results are summarized in Table 1.
In conclusion, we have developed a very simple, inexpensive, nontoxic, and
environmentally friendly method for the acylation of primary amines. The presence
of the SO3H group in all synthesized amides ensures their good water solubility and
thus their application as tracers in georeservoirs. In particular, there is not a lot of
information related to the synthesis of water-soluble amides.
EXPERIMENTAL
All chemicals, reagents, and solvents were used as received from commercial
sources without further purification. 1H NMR and 13C NMR spectra were recorded
in dimethylsulfoxide (DMSO-d6) on a 300-MHz liquid-state Bruker spectrometer.
The splitting patterns are annotated as follows: s (singlet), d (doublet), t (triplet),
q (quartet), and m (multiplet). The products were also confirmed by electrospray
ionization–mass spectrometry (ESI-MS) (instrumentation is described in No¨dler
et al.[11]). Preparative column chromatography was carried out on glass columns
of different sizes packed with silica gel: Merck 60 (0.035–0.070 mm).
General Procedure of Method A
Primary amino sulfonic acid (2.5 mmol) is suspended in brine (scale: 1 g of
sodium chloride in 3 ml of water) and then an equivalent amount of acid chloride
in acetone (1:1) is added dropwise during 15 min. Saturated sodium bicarbonate
solution (10 mmol) is added, and the reaction mixture is stirred for a further period
of 12 h. From the sodium salt, the corresponding product is obtained by the usual
acidic workup (acidification is accomplished by concentrated sulfuric acid) followed
by washing with hot water to remove traces of carboxylic acid created during the
reaction.
General Procedure of Method B
Primary amino sulfonic acid (2.5 mmol) is suspended in ethyl acetate (50 mL)
and then an equivalent amount of acid chloride is added. After the reaction had been
stirred intensively for 10 min at room temperature, 10 mmol of triethylamine is
added. The mixture is stirred overnight, and then the solvent is removed under
reduced pressure. The crude product is washed several times with ethyl acetate
and subsequently purified by column chromatography (hexane=ethyl acetate, 1:5
and then methanol).

SYNTHESIS OF WATER-SOLUBLE AMIDES
139
Spectral Data for Selected Compounds
4-[(Naphthalen-1-ylcarbonyl)amino]benzenesulfonic acid (2). 1H NMR
(300 MHz, DMSO-d6) d, ppm, 10.60 (s, 1H), 8.21–8.15 (m, 1H), 8.07 (d, J ¼ 8.4 Hz,
Hz, 1H), 8.04–7.99 (m, 1H), 7.79–7.74 (m, 3H), 7.64–7.56 (m, 5H); 13C NMR
(300 MHz, DMSO-d6) d, ppm, 167.27, 143.51, 139.35, 134.58, 133.11, 130.07,
129.61, 128.26, 126.93, 126.28, 126.05, 125.44, 125.03, 124.96, 118.79. ESI-MS:
m=z ¼ 326 [MꢀH]ꢀ.
4-[(Diphenylacetyl)amino]benzenesulfonic acid (7). 1H NMR (300 MHz,
DMSO-d6) d, ppm, 10.68 (s, 1H), 7.59 (d, J ¼ 8.7 Hz, 2H), 7.52 (d, J ¼ 8.7 Hz, 2H),
7.39–7.30 (m, 8H), 7.28–7.21 (m, 2H), 5.31 (s, 1H); 13C NMR (300 MHz, DMSO-d6)
d, ppm, 169.92, 141.33, 139.93, 139.09, 128.44, 128.21, 126.67, 125.97, 118.15, 56.98.
ESI-MS: m=z ¼ 366 [MꢀH]ꢀ.
3-Methyl-4-(pentanoylamino)benzenesulfonic acid (10). 1H NMR
(300 MHz, DMSO-d6) d, ppm, 9.25 (s, 1H), 7.42 (s, 1H), 7.36 (dd, J ¼ 8.1, 1.5 Hz,
1H), 7.31 (d, J ¼ 8.1 Hz, 1H), 2.33 (t, J ¼ 7.4 Hz, 2H), 2.18 (s, 3H), 1.63–1.53 (m,
2H), 1.44–1.26 (m, 2H), 0.91 (t, J ¼ 7.4 Hz, 3H); 13C NMR (300 MHz, DMSO-d6)
d, ppm, 171.09, 144.83, 136.45, 130.61, 127.34, 123.99, 123.07, 35.37, 27.33, 21.70,
17.77, 13.61. ESI-MS: m=z ¼ 270 [MꢀH]ꢀ.
4-[(2,2-Dimethylpropanoyl)amino]naphthalene-1-sulfonic acid (17). 1H
NMR (300 MHz, DMSO-d6) d, ppm, 9.45 (s, 1H), 8.92–8.86 (m, 1H), 7.94 (d,
J ¼ 7.8 Hz, 1H), 7.87–7.83 (m, 1H), 7.55–7.49 (m, 2H), 7.32 (d, J ¼ 7.8 Hz, 1H),
1.34 (s, 9H); 13C NMR (300 MHz, DMSO-d6) d, ppm, 177.13, 141.96, 135.13,
129.74, 129.62, 127.76, 125.33, 125.25, 123.99, 122.80, 122.38, 38.83, 27.37. ESI-MS:
m=z ¼ 306 [MꢀH]ꢀ.
SUPPORTING INFORMATION
Full spectroscopic and characterization data including MS (triple quadrupole
mass spectroscopy) are given in the supporting materials, available online.
ACKNOWLEDGMENT
The presented study was funded by the German Ministry of Environment
(BMU) (promotional reference no. 0325417, Reaktherm). This support is gratefully
acknowledged.
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