Sustainable Carboxylation of Diamines with Hydrogen Carbonate

Article abstract of DOI:10.1021/acs.oprd.8b00229

A protocol for the carboxylation of diamines employing quaternary ammonium hydrogen carbonates as C1 source is presented. The approach is used to obtain industrially relevant bis-O-alkyl carbamates with diverse structural features in very high yield, even on gram scale. The quaternary ammonium salts, formally acting as "transporters" of the carboxylating agent, can be recovered after the reaction, and recycled with high efficiency. Regeneration of the hydrogen carbonates on ion-exchange resin grants excellent atom economy in the process.

Full text of DOI:10.1021/acs.oprd.8b00229

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Communication
Sustainable carboxylation of diamines with hydrogen carbonate
Gianpiero Forte, Isabella Chiarotto, Frank Richter, Vinh Trieu, and Marta Feroci
Org. Process Res. Dev., Just Accepted Manuscript • DOI: 10.1021/acs.oprd.8b00229 • Publication Date (Web): 31 Aug 2018
Downloaded from http://pubs.acs.org on September 2, 2018
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Sustainable carboxylation of diamines with
hydrogen carbonate
Gianpiero Forte,a,* Isabella Chiarotto,a Frank Richter,b Vinh Trieu,b Marta Feroci a,*
a Dipartimento di Scienze di Base e Applicate per l'Ingegneria, Sapienza Università di Roma, Via del Castro
Laurenziano 7, 00161 Roma, Italy. *E-mail: gianpiero.forte@uniroma1.it; marta.feroci@uniroma1.it
b Covestro Deutschland AG, Kaiser-Wilhelm-Allee 60, 51365 Leverkusen, Germany
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TABLE OF CONTENT
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Abstract. A protocol for the carboxylation of diamines employing quaternary ammonium
hydrogen carbonates as C1 source is presented. The approach is used to obtain
industrially relevant bis-O-alkyl carbamates with diverse structural features in very high
yield, even on gram scale. The quaternary ammonium salts – formally acting as
“transporters” of the carboxylating agent – can be recovered after the reaction, and
recycled with high efficiency. Regeneration of the hydrogen carbonates on ion exchange
resin grants excellent atom economy in the process.
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Keywords: Carboxylation, carbamates, diamines, green chemistry, atom economy.
INTRODUCTION
The environmental impact of production processes is a topic of increasing awareness in
current research and development.1 This has fueled the interest towards under-explored
approaches to chemical synthesis, building up the idea of green and sustainable
chemistry.2 A substantial number of studies on the reactivity of carbon dioxide, along with
the amount of funding consistently allocated to develop reactions to exploit CO2, well
attests this situation.3 Carbon dioxide is indeed regarded as the primary anthropogenic
contribution to the greenhouse effect. As of 2013, its concentration in the atmosphere has
exceeded the record value of 400 ppm,4 raising major concerns about impacts on climate
change. To prevent irreversible environmental issues, recent international agreements
called for an urgent and dramatic cut in global emissions of CO2.5
Resources spent on strategies that limit the release of carbon dioxide into the environment
have since considerably increased.6 On the other hand, CO2 represents a cheap and
readily accessible carbon source,7 and the prospect of capturing the gas from industrial
exhausts has driven the quest for viable methods to overcome its inert nature. These
methods generally require harsh reaction conditions, such as high pressure or the
presence of strong nucleophiles, and appear quite cumbersome to operate on a large
scale. Most importantly, they often make use of metal catalysis, raising concerns on the
environmental impact of waste management.
As part of our ongoing interest in carbamate chemistry, we are committed to investigate
scalable protocols for a sustainable transformation of diamines into alkyl carbamates –
direct precursors of di-isocyanates, and key intermediates in the manufacturing process of
polyurethanes, whose global market is expected to top USD 105 billion by 2025.8 Our
goals are two-fold: (1) devise potential approaches to activate carbon dioxide for the
synthesis of bis-O-alkyl carbamates; (2) optimize existing protocols in the perspective of
industrial applications: taking into account the nature of reaction byproducts, and the
possibility to recycle solvents and catalysts; avoiding health hazards; addressing issues of
scalability and costs associated with the process.9
We recently described the synthesis of bis-O-butyl carbamates from diamines and carbon
dioxide at atmospheric pressure, using butyl chloride as alternative to more harmful and
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expensive bromides or iodides.10 The protocol involves the pre-activation of CO2 on a
copper cathode under very mild conditions. Collateral reactions, however, make the atom
economy of such electrochemical activation highly questionable, while current non-
electrochemical approaches to obtain carbamates from CO2 need further optimization to
be applicable on large scale.11
Here we report that tetraalkylammonium hydrogen carbonates, prepared from the
corresponding chlorides, can efficiently carboxylate diamines. Notably, formed
tetraalkylammonium chlorides can be recovered after the synthesis of carbamate esters,
and used to regenerate the carboxylating agent with excellent atom economy in the overall
process.12
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RESULTS AND DISCUSSION
Reduction of CO2 on copper electrodes in polar aprotic solvents, such as acetonitrile,
mainly yields carbonates.13 Without additional bases, they react with amines to
quantitatively form carbamate anions, whose nucleophilic behavior is particularly
enhanced when tetraalkylammonium salts are used during the electrolysis.14 This
activation method broadly benefits from the practical advantages of electrochemistry,
including the use of mild conditions, and the absence of stoichiometric reductants.15
However, drawbacks like large initial amount of supporting electrolytes, and products of
anodic reactions may hamper the effective sustainability of the protocol in industrial
applications.
Earlier studies from our group demonstrated that tetraethylammonium hydrogen carbonate
(TEAHC) can carboxylate amines as efficiently as carbonates generated in the
electrochemical reduction of CO2.16 TEAHC can be conveniently prepared from the
corresponding chloride (TEACl) in a two-step process (Scheme 1, panel A),17 and is a
promising alternative to overcome the aforementioned issues.
Scheme 1. Synthesis of TEAHC (A); synthesis of butyl carbamates using TEAHC for the
carboxylation of amines (B).
Our investigation began with assessing the reactivity of TEAHC towards diamines –
maintaining ratios optimized for monoamines (1.5 equiv. of TEAHC per amine group), but
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using 2.0 equiv. of butyl chloride instead of 5.0 equiv. of ethyl iodide per diamine – to rule
out the unwanted formation of partially carboxylated, or N-alkylated, byproducts.
Hexamethylenediamine (HMDA) was used to carry out the study because of the symmetric
structure, which facilitates the NMR analysis of reaction products. Under these conditions
(see experimental section), bis-O-butyl carbamate ester 1 is isolated in 92% yield as pure
product (Scheme 2). The reaction can also be transferred to gram scale with a negligible
performance loss: 1 is indeed obtained in 90% yield (19.8 g) when 70.0 millimoles of
HMDA are carboxylated with TEAHC.
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It is interesting to notice that a stoichiometric amount of TEACl is formed during the
alkylation step with butyl chloride (Scheme 1, panel B). Being the starting material for the
synthesis of the hydrogen carbonate, TEACl can be recycled for subsequent reactions.
The negligible solubility of both ammonium salts in diethyl ether largely facilitates their
recovery, as solvent washings allow to separate the carbamate. In Table 1, column A, the
yield of 1 for subsequent reactions are reported. After product extraction at the end of each
run, the remaining solids were dried under high vacuum, then treated according to
Scheme 1. A drop from 90% to 50% in the yield of 1 already occurs in the first recycling
experiment. Slight improvements were observed by filtering off insoluble KCl after the
residue was dissolved in methanol. Yet results remain quite far from being satisfactory,
with the yield of 1 dropping to 65% between run four and five (Table 1, column B).
Scheme 2. Synthesis of dibutyl hexane-1,6-diyldicarbamate (1) using TEAHC as carboxylating
agent. TEAHC: tetraalkylammonium hydrogen carbonate.
Excellent efficiency in recycling experiments was achieved when anion exchange resin
Amberlite IRA-400 was utilized to convert TEACl to TEAHC (Table 1, column C). The resin
is commercially available in chloride form, and stable to basic conditions. It is readily
activated for our purposes by treatment with sodium hydrogen carbonate,18 which can be
prepared by bubbling CO2 into aqueous solutions of sodium hydroxide. Besides leading to
recycle TEACl up to four times without any appreciable loss in the the yield of 1, the use of
these resins is generally regarded as a “green” asset for sustainable applications, and they
are currently employed in a wide range of industrial processes.19 By the end of five
subsequent reactions with such recycling approach, we calculated a 6.5% total loss of
active TEAHC, which may be ascribed to Hofmann elimination on TEA cation at high
temperatures.20
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Table 1. Regeneration of carboxylating agent. Yield of 1 for the reaction in Scheme 1. a
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TEAHC: tetraethylammonium hydrogen carbonate; SpiroHC: 5-azoniaspiro[4.4]nonane hydrogen carbonate.
a
Synthesis of dibutyl hexane-1,6-diyldicarbamate from hexamethylenediamine (0.5 mmol), quaternary
ammonium hydrogen carbonate (1.5 mmol) and butyl chloride (2.0 mmol) under experimental conditions
b
reported in Scheme 1. For each set of experiments, the carboxylating agent is reported in parentheses;
c
isolated product; after product extraction, the remaining solids were dried under vacuum and used to
d
regenerate TEAHC; prior to regenerate TEAHC, the remaining solids were dissolved in methanol, and the
impurities filtered off; e the remaining solids were dissolved in water and passed on Amberlite IRA-400 resin,
activated as described in the Experimental Section.
We reasoned that our process could benefit from the high thermal stability of spirocyclic
ammonium salts recently reported.21 In a set of experiments TEAHC was replaced by 5-
azoniaspiro[4.4]nonane hydrogen carbonate (SpiroHC), whose corresponding chloride 2
can be conveniently prepared from pyrrolidine (Scheme 3). The data (Table 1, column D)
indicate results comparable to the use of TEAHC, even in gram scale carboxylations: 88%
yield (1.4 g) of 1 is indeed obtained from 5.0 millimoles of HMDA (see SI). However we
calculated up to 27% total loss of active SpiroHC after five subsequent reactions.
Scheme 3. Synthesis of 5-azoniaspiro[4.4]nonane chloride (2).
Because diamines with diverse structural features are precursors of industrially important
carbamates, we tested the range of applicability of carboxylation with TEAHC and SpiroHC
on compounds reported in Table 2. Both salts efficiently react with aliphatic diamines,
yielding results comparable to those obtained with electrochemically activated CO2 (entries
1-3). Benzyl diamines are slightly affected by inductive effect of the aromatic ring, resulting
in decreased efficiency of the carboxylation process, and lower yield of the final carbamate
(entry 4). Unexpected drop in performance of the reaction with SpiroHC is observed in this
case. The spirocyclic cation appears to play a detrimental role that we find hard to
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rationalize at this stage. Aromatic diamines suffer from a poor nucleophilic character, and
cannot be carboxylated either with TEAHC or SpiroHC under our mild experimental
conditions. As observed already in the case of electrochemically activated CO2, formation
of very low amounts of carbamate can only be observed when ethyl iodide is used in the
alkylation step (entries 5-6).
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Table 2. Carboxylation of different diamines using TEAHC or SpiroHC.a
TEAHC: tetraethylammonium hydrogen carbonate; SpiroHC: 5-azoniaspiro[4.4]nonane hydrogen carbonate.
a
Diamines (0.5 mmol) were treated with quaternary ammonium hydrogen carbonate (1.5 mmol), then with
butyl chloride (2.0 mmol) at 80 °C. b isolated product. The yield for each first recycling experiment is reported
c
in parentheses; CO2 activated on a copper cathode prior to reaction with the diamine. For further details,
see ref. 10; d ethyl iodide used in the alkylation step (room temperature, overnight).
CONCLUSIONS
In conclusion, quaternary ammonium hydrogen carbonates carboxylate benzyl diamines
with good yield, and aliphatic diamines with high to very high yield even on gram scale. We
proved that anion exchange resins can be repeatedly used to obtain the carboxylating
agent from the corresponding chloride, which is regenerated in the synthesis of bis-O-alkyl
carbamates. Quaternary ammonium ions thus formally act as “transporters” of an activated
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form of CO2, and can successfully be recycled to achieve a sustainable process with
excellent atom economy.
TEAHC and SpiroHC are both effective carboxylating agents towards diamines, with the
former giving generally better results when used in the synthesis of bis-O-alkyl
carbamates. Active SpiroHC, supposedly more stable to temperature, experiences a
significant loss during recycling experiments; by contrast, TEAHC is regenerated in
virtually quantitative way.
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EXPERIMENTAL SECTION
Materials and methods. NMR spectra were recorded on a Bruker AC 200
spectrometer, using CDCl3 as internal standard. HPLC grade acetonitrile (≥ 99.9%, Sigma-
Aldrich) was used in all the experiments. Tetraethylammonium chloride (≥ 99.9%, Sigma-
Aldrich) was stored in a desiccator. All other reagents were used as received.
Each described experiment was repeated at least three times, and the yields (reported as
average values in the manuscript) are calculated on the amount of isolated pure product.
Amberlite IRA-400 resin (chloride form, Sigma-Aldrich) was loaded with water into a glass
column (height: 18 cm; internal diameter: 1 cm), and activated as follows:
• washed with water until AgNO3 test was negative to chlorides (only when used for the
first time);
• slowly washed with 20 ml of NaHCO3 solution (1.0 mol/L in water);
• washed with water until HCl test for bicarbonates was negative.
Synthesis of 5-azoniaspiro[4.4]nonane chloride, 2. KOH (1.12 g, 20.0 mmol) was
stirred in water (15 ml) at 100 °C. After 10 min, pyrrolidine (1.65 ml, 20.0 mmol) was slowly
added, followed by slow addition of 1,4-dichlorobutane (2.2 ml, 20.0 mmol). The reaction
mixture was kept under stirring at 100 °C for 18h, then overnight at room temperature. The
solvent was evaporated under reduced pressure to obtain a solid residue, which was
dissolved in CHCl3 and filtrated. CHCl3 was evaporated under vacuum to afford 2.85 g of
pure chloride 2 (88% yield).
Preparation of TEAHC and SpiroHC on Amberlite resin. Tetraethylammonium or 5-
azoniaspiro[4.4]nonane chloride (1.5 mmol) in 2.0 ml of water was slowly passed through
a column containing the hydrogencarbonate form of the ion-exchange resin (see Materials
and Methods section). The column was washed with water until 50 ml of solution were
collected. The solvent was removed under reduced pressure to afford TEAHC or SpiroHC
as a white solid, which was kept overnight under high vacuum.
General protocol to the synthesis of bis-O-butylcarbamates using TEAHC or
SpiroHC. In a 50 ml round bottom flask, TEAHC or SpiroHC (1.5 mmol) was dissolved in
12 ml of acetonitrile. The diamine (0.5 mmol, dissolved in 1 ml of acetonitrile) was added,
and the reaction was allowed to stir at room temperature for 1h. Butyl chloride (2.0 mmol)
was added, and the mixture stirred at 80 °C for 3h. The solvent was removed under
reduced pressure, and the resulting residue was extracted with diethyl ether (3 × 40 ml).
The collected organic fractions were concentrated to dryness to yield the pure butyl
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dicarbamate ester, while the diethyl ether used for the extractions was condensed and
used in following experiments.
Carboxylation scale-up with TEAHC. Synthesis of dibutyl hexane-1,6-
diyldicarbamate, 1. TEAHC (40.2 g, 210.0 mmol) was dissolved in 1.3 L of acetonitrile,
and hexamethylenediamine (8.1 g, 70.0 mmol, dissolved in 70 ml of acetonitrile) was
added. The solution was allowed to stir at room temperature for 2h. Butyl chloride (29 ml,
280.0 mmol) was added, and the reaction mixture heated at 80 °C for 3h. The solvent was
removed under reduced pressure, and the resulting residue was extracted with ethyl
acetate (3 × 300 ml). The collected organic fractions were concentrated to dryness to
afford 19.8 g of the product (90% yield).
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Recovery and recycle of TEACl or chloride 2. The solid residue, after ethereal
extractions, was dried in vacuo, dissolved in 2 ml of water, and treated with the resin to
regenerate TEAHC or SpiroHC as described above.
ACKNOWLEDGEMENTS
This work was financially supported by Covestro Deutschland AG, Sapienza Università di
Roma and MIUR (Ministero dell'Istruzione, dell'Università e della Ricerca).
ASSOCIATED CONTENT
Supporting Information. Reported procedure for TEAHC preparation from TEACl without
1
using Amberlite resin; carboxylation scale-up with SpiroHC; H, 13C NMR spectra and
characterization of synthesized compounds (PDF).
The authors declare no competing financial interests.
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