Fluoride-Catalyzed Deblocking: A Route to Polymeric Urethanes

Article abstract of DOI:10.1002/anie.201800795

We report a fluoride-catalyzed deblocking of urethanes as “blocked” isocyanates. Organic and inorganic sources of fluoride ion proved effective for deblocking urethanes and for converting polyurethanes to small molecules. Distinct from conventional deblocking chemistry involving organometallic compounds and high temperatures, the method we describe is metal-free and operates at or slightly above room temperature. The use of fluorescent blocking agents enabled visual and spectroscopic monitoring of blocking/deblocking reactions, and the selected conditions proved applicable to urethanes containing a variety of blocking groups. The method additionally enabled a one pot deblocking and polymerization with α,ω-diols. Overall, this deblocking/polymerization strategy offers a convenient and efficient solution to problems that have limited the breadth of applications of polyurethane chemistry.

Full text of DOI:10.1002/anie.201800795

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Accepted Article
Title: Fluoride-Catalyzed Deblocking as a New Route to Polymeric
Urethanes
Authors: Madhu Sheri, Umesh Choudhary, Sunitha Grandhee, and
Todd Shannon Emrick
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201800795
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10.1002/anie.201800795
Angewandte Chemie International Edition
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Fluoride-Catalyzed Deblocking as a New Route to Polymeric
Urethanes
Madhu Sheri,† Umesh Choudhary,† Sunitha Grandhee,‡ and Todd Emrick†*
shown in Figure 1, blocked isocyanates 2a-e were prepared by
reacting toluene diisocyanate (TDI) with selected alcohols in
anhydrous dimethylformamide (DMF). The reactions were
monitored by infrared spectroscopy, showing the loss of NCO
signals (2265 cm-1) and emergence of bands for the carbonyl
(1710-1716 cm-1) and N-H (3326 cm-1) groups of urethanes. For
the pyrene-blocked sample, 1H NMR spectroscopy revealed
aromatic resonances from 8.05 to 8.35 ppm (from pyrene) and
7.05-7.25 ppm (from TDI), as well as broad N-H resonances at
9.05 and 9.75 ppm (Figures S1-S23). The fluorescence spectrum
of pyrene-blocked TDI exhibited characteristic vibronic bands at
395 nm (0-0 transition) and 415 nm (0-2 transition), as well as
excimer emission at 480 nm.25-26
Abstract: We report a fluoride-catalyzed deblocking of urethanes as
“blocked” isocyanates. Organic and inorganic sources of fluoride ion
proved effective for deblocking urethanes and for converting
polyurethanes to small molecules. Distinct from conventional
deblocking chemistry involving organometallic compounds and high
temperatures, the method we describe is metal-free and operates at
or slightly above room temperature. The use of fluorescent blocking
agents enabled visual and spectroscopic monitoring of
blocking/deblocking reactions, and the selected conditions proved
applicable to urethanes containing a variety of blocking groups. The
method additionally enabled a one pot deblocking and polymerization
with -diols. Overall, this deblocking/polymerization strategy offers
a convenient and efficient solution to problems that have limited the
breadth of applications of polyurethane chemistry.
With respect to the deblocking mechanism, we note that
anion coordination depends on ionic and dipolar interactions.24-28
The literature describes fluoride ion as a versatile reagent for
ureas, involving N-H deprotonation, formation of bifluoride anion
-
(HF2 ), and subsequent structural transformations.29-31 For
Since their discovery by Bayer and co-workers,
polyurethane-based materials have elevated to a position of
major societal importance.1-2 The polyurethane market continues
rapid growth, owing to the superior properties of these polymers
in numerous applications,3-5 including as sealants,6-7 adhesives,8-
example, the combination of fluoride ion with aromatic ureas
produced colorimetric chemosensors, with color changes induced
by N-H deprotonation.32-34 Unlike ureas, N-H deprotonation of
urethanes can trigger elimination to generate isocyanates by
Hofmann-type rearrangement.35-36 We investigated urethane
deblocking using fluoride, chloride, bromide, and iodide salts. As
illustrated in Figure 2, addition of 5 mole percent of tetra-n-
butylammonium fluoride (n-Bu4NF) to pyrene-blocked TDI in DMF
led to an immediate loss of pyrene fluorescence, due to
elimination and precipitation of pyrene. Similar experiments
performed with n-Bu4NCl produced only a small fluorescence
reduction, while n-Bu4NBr and n-Bu4NI afforded no visual change
to the solution. DMF solutions of CsF performed similarly to n-
Bu4NF, prompting our focus on the effect of fluoride ion on
urethane deblocking and catalysis of polyurethane formation from
blocked isocyanate monomers.
9
foams,10-11 and coatings.12-13 Polyurethane properties are
tailored by monomer selection,14-16 involving diisocyanates, diols,
and/or polyols.17 However, even conventional polyurethane
chemistry carries significant challenges, including moisture
sensitivity and toxicity of the isocyanate monomers.18-19 “Blocked”
isocyanates, obtained by reacting isocyanates with alcohols, are
more stable and less toxic, and serve as isocyanate surrogates in
polyurethane synthesis.20-22 At elevated temperature and in the
presence of a catalyst, losing the blocking group regenerates the
isocyanate, which polymerizes with diols or polyols. This
chemistry presents its own complexities by requiring high
deblocking temperatures and variable success depending on the
selected isocyanate, solvent, catalyst, and blocking moiety.17-19
Solvents and co-reactants induce disparities in deblocking
temperatures, with higher temperatures promoting isocyanurate
formation and degradation.17,23 As such, efficient new methods for
isocyanate deblocking are needed on both a small and large scale.
After addition of n-Bu4NF to a DMF solution of pyrene-
blocked TDI, FTIR analysis of an aliquot taken from the reaction
mixture showed the return of a characteristic NCO stretching band
at 2265 cm-1 (Figure 3a); additionally, 1H NMR spectroscopy
confirmed the disappearance of N-H signals from 9.1-9.8 ppm,
while signals typical of TDI re-emerged (Figures S47-S58). Upon
addition of the phenolic TokyoGreen (TG),37-38 a rapid color
change, from blue to yellow, was observed as the generated
isocyanate was consumed. The TG-blocked TDI products were
obtained in 75-80% yield, with structural confirmation by FTIR, 1H
NMR, ESI-MS, and UV-Vis spectroscopy (Figure 3). FTIR
spectroscopy showed characteristic bands at 1712 cm-1 and 3326
Here we report a mild and effective route to isocyanate
deblocking involving halide ions, and especially fluoride salts.
This methodology was tested successfully on a variety of
urethanes, including 1) fluorescent versions that enabled facile
spectroscopic characterization of blocking group exchange and 2)
precursors to polyurethanes and cross-linked polyurethanes
using sequential deblocking and polymerization. Our selection of
fluoride ion for these reactions exploits its strong hydrogen
bonding interactions with N-H groups of organic compounds.24 As
1
cm-1 for the carbonyl and N-H groups, respectively and H NMR
showed signals corresponding to TG (6.45-7.80 ppm),
characteristic TDI resonances from 7.20-7.30 ppm, and broad NH
resonances at 9.10 and 9.62 ppm (Figure S51); these data
confirmed the desired deblocking and nucleophile exchange. The
TG-blocked compound had a bright yellow fluorescence under
UV-light, with absorption and photoluminescence (PL) emission
at 520 nm and 540 nm, respectively (Figure 3b).
Dr. M. Sheri, Dr. U. Choudhary, Prof. T. Emrick
Polymer Science and Engineering Department, University of
Massachusetts Amherst, 120 Governors Drive, Amherst, MA 01003,
United States.
Email: tsemrick@mail.pse.umass.edu
Dr. S. Grandhee
BASF Corporation, 1609 Biddle Avenue, Wyandotte, Michigan, 48192
United States.
Fluoride-catalyzed deblocking was then tested on
polyurethane 2f (Figure 1) that had been prepared from TDI and
triethylene glycol (Mn ~30 kDa, Figure 4). This was performed in
anhydrous DMF with 5 mole percent n-Bu4NF or CsF, followed by
addition of 2 molar equivalents TG (based on TDI) to afford a
product which was confirmed spectroscopically (by 1H NMR,
Supporting information is given in a link at the end of the document.
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10.1002/anie.201800795
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Figure 2. Fluoride-catalyzed urethane exchange, from
pyrene-to-TG, with photographs of the corresponding solutions.
FTIR, UV-Vis) to have undergone deblocking, and which by
GPC showed a reduction in molecular weight from the original
polyurethane to the low molecular weight bis-substituted TDI
(Figure 4b) in 76% yield. Similar experiments were conducted on
conventional blocked isocyanates prepared from TDI or
methylene diphenyl diisocyanate (MDI) with propargyl alcohol,
isopropanol, and tert-butanol (Figures S1-S46). The relatively
low boiling points of these alcohols allowed their removal under
vacuum after deblocking, driving the reactions towards product.
In a typical reaction, after 30 minutes stirring under vacuum (500
mbar), the mixture was returned to ambient pressure, water was
added, and the product was recovered as an orange solid in 75-
80% yield. 1H NMR spectroscopy showed a loss of signals
corresponding to the original blocking groups as well as the
Figure 3. FTIR spectra of (a) pyrene-blocked TDI (blue),
deblocked product (green), and TG-substituted product (red); (b)
UV-Vis and PL spectra of pyrene- and TG-blocked TDI in DMF.
appearance
of
TG
resonances
(Figures S51-S58).
Approximately 5 mol% F- proved optimal – using lower amounts
(2-3 mol %) required longer reaction times (>5 hours) or led to
only partial deblocking.
The stability of blocked isocyanates makes them attractive for
long-term storage and reducing exposure/toxicity concerns.
Coupling those advantages with convenient, catalytic
polymerization methodology is attractive for the preparation of
polyurethanes. As shown in Figure 5, blocked isocyanates 2a-e
were used to prepare polyurethanes starting from a slight molar
Figure 4. (a) Fluoride-catalyzed deblocking of polyurethane 2f
with TG; (b) GPC traces of 2f (red) and TG-blocked TDI (blue).
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excess of the blocked structure relative to diol. Attempted
polymerizations at room temperature led to little increase in
molecular weight, but at 50 °C the polymerizations proceeded to
to afford 4a-e with Mn values of 8-10 kDa. When the
polymerizations were conducted at 50 °C for 6 hours under
vacuum (500 mbar), molecular weight values were higher (Mn
reaching 27 kDa) (Figure 5b) and PDIs ranged from 2.3-3.1.
Precipitation was observed during the polymerizations, and
polymers 4a-e were obtained as white solids in 60-75% yield;
notably, in the case of 4e, residual 1-pyrenemethanol was
removed by extraction into CH2Cl2 and the polyurethane obtained
had no fluorescent signature, confirming the absence of the
original blocking group in the structure. Similar experiments were
conducted on blocked isocyanates prepared from MDI (Figures
S63-S70). These polymerizations proceeded
generated isocyanate. Oxime blocking agents undergo
intramolecular cyclization to yield 3-methylisoxazol-5-one.39-40 We
synthesized oxime-blocked isocyanate 2d, derived from ethyl
acetoacetate oxime (EAO), for fluoride-catalyzed deblocking
(Figure 6). Addition of F- caused deblocking and release of EAO,
and the generated isocyanate was subsequently treated with 4-
methylumbelliferone to form the bright blue fluorescent coumarin-
blocked isocyanate. The product was isolated in 86% yield and
characterized by NMR, FTIR, UV-Vis, and fluorescence
spectroscopy (Figures S71-S74). Notably, polymerizations
conducted with 2d at 50 oC without vacuum afforded polyurethane
with Mn value of 28 kDa in good yield 65-75% since removal of
deblocked structure from solution is unnecessary (Table 1).
Figure 6. Fluoride-catalyzed urethane exchange, from oxime-to-
coumarin, and photographs of the corresponding solutions.
This fluoride-catalyzed methodology is anticipated to be
applicable to many types of polyurethane structures and
preparative methods. As outlined in Figure 7, when a solution of
blocked isocyanate 2d (3 mmol) in DMF was treated with 5 mol%
n-Bu4NF or CsF, followed by addition of 1,1,1-trishydroxymethyl
ethane (2 mmol), an insoluble white gel formed as a result of this
Figure 5. (a) Preparation of polyurethanes 4a-e by deblocking
and polymerization; (b) representative GPC trace of polyurethane
4a (DMF as mobile phase); (c) temporal evolution of molecular
weight of polymer 4a (estimated by GPC).
A2
+
B3 polymerization (Figure S75). Going forward,
polyurethane-based thin films, coatings, foams, and printed
objects from blocked urethanes are anticipated to be similarly
amenable to this halide-catalyzed process.
Table 1. Number-average molecular weight (Mn) and PDI values
of 4a-e estimated by GPC with DMF as mobile phase (calibrated
against polystyrene standards). aYields after precipitation.
Figure 7. Preparation of cross-linked polyurethane by fluoride-
catalyzed deblocking of oxime-blocked TDI (2d) and
polymerization with 1,1,1-trishydroxymethylethane.
generated polyurethanes 4f-j with Mn values of 12-18 kDa (Table
S1) and with PDI 1.2-1.9. These fluoride-catalyzed polyurethane
syntheses, monitored by GPC (Figure 5c), exhibited classic step-
growth polymerization kinetics, with little molecular weight
increase early in the reaction timeframe, and rapid molecular
weight growth in the later stages. These polymerizations predict
easy scalability, as they were conducted easily at the two-gram
scale.
In summary, we described a new method of urethane
deblocking and polyurethane formation by exploiting fluoride ion
as an efficient and mild catalyst. The reactions are enabled by
the propensity of fluoride anion to engage in urethane deblocking
and generate reactive isocyanates for polymerization. Our
selection of fluorescent blocking agents enabled easy visual and
spectroscopic monitoring of these reactions, and we anticipate
the methods described to be amenable to numerous polyurethane
preparations and formulations.
We also examined
a blocking agent which, following
deblocking, undergoes chemistry to render it unreactive with the
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Acknowledgements
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The authors acknowledge financial support from BASF-NORA
and appreciate the helpful discussions of Drs. M. Schroeder, K.
Gust, and R. Kumar.
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Keywords: blocking • fluoride-catalyzed deblocking •
fluorescence • polyurethane • cross-linked polyurethane
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Entry for the Table of Contents
COMMUNICATION
Madhu Sheri, Umesh
Choudhary, Sunitha
Grandhee and Todd
Emrick,*
Page No. – Page No.
Fluoride-Catalyzed
Deblocking as a New
Route to Polymeric
Urethanes
We report a new method of urethane deblocking and polyurethane formation using fluoride ion
as an efficient catalyst. Fluorescent blocking groups enabled easy visual and spectroscopic
monitoring of blocking/deblocking reactions, and we anticipate that this method will offer a
convenient and efficient solution to problems that have limited the breadth of applications of
polyurethane chemistry.
This article is protected by copyright. All rights reserved.