Stabilization of the hindered urea bond through de-tert-butylation

Article abstract of DOI:10.1039/d1cc00715g

We report the discovery of an acid-assisted de-tert-butylation reaction that can instantly “turn off” the dynamicity of hindered urea bonds (HUBs) and thus broaden their applications. The reaction is demonstrated to be widely applicable to different hindered urea substrates, leading to improved chemical stabilities and mechanical properties of HUB-containing materials.

Full text of DOI:10.1039/d1cc00715g

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Stabilization of the hindered urea bond through
de-tert-butylation†
Cite this: Chem. Commun., 2021,
57, 3812
a
Yingfeng Yang,a Hanze Ying,
Yunchao Jia,b Yingying Chena and
a
Received 6th February 2021,
Accepted 9th March 2021
Jianjun Cheng
*
DOI: 10.1039/d1cc00715g
rsc.li/chemcomm
We report the discovery of an acid-assisted de-tert-butylation N-substituent renders the urea bond dynamic.21 Based on this
reaction that can instantly ‘‘turn off’’ the dynamicity of hindered chemistry, hindered polyurea materials which display some
urea bonds (HUBs) and thus broaden their applications. The reac- unique features as opposed to traditional polyurea were developed,
tion is demonstrated to be widely applicable to different hindered such as materials with self-healing properties, multiple shape-
urea substrates, leading to improved chemical stabilities and memory effect, reprocessability and recyclability, as reported by
mechanical properties of HUB-containing materials.
us21–26 and others.27–29 However, stability issues can sometimes
severely limit their applications. Since the dynamicity of the
Dynamic covalent chemistry (DCC),1,2 characterized by the hindered urea bond is induced by the bulky N-substituent, one
reversible breaking and formation of covalent bonds, is a relatively straightforward strategy to ‘‘turn off’’ the dynamicity could
powerful tool that enables the synthesis of novel macrocycles, be removing the tert-butyl group as shown in Scheme 1. Here we
molecular cages, knots and covalent organic frameworks.3–11 It report the discovery of acid-assisted de-tert-butylation reaction that
has also been incorporated into polymeric networks, which can instantly ‘‘turn off’’ the reversibility of the hindered urea bond
endows the materials with functions like self-healing, shape (HUB). With the use of acid, the carbonyl group of HUB is
memory, stimuli responsiveness, reprocessability and recycl- protonated, followed by the formation of tert-butyl carbocations
ability.12–17 Despite these interesting features, structures with and rearrangement of the proton for the formation of a urea bond
DCC incorporated often suffer from low stability, because of the that has no dynamicity. We demonstrated that this de-tert-
endogenous bond dynamicity. This problem can be circum- butylation reaction is easily attainable in small molecules, and
vented, however, by ‘‘turning off’’ the bond dynamicity to linear/crosslinked polymers.
achieve stabilized structures and substrate properties. How-
The acid-assisted de-tert-butylation of HUBs was discovered
ever, only a few DCCs have feasible chemistry tools to allow easy unexpectedly in our research. While we were studying the
‘‘turning off’’ of the DCC bond dynamicity, such as stabilizing influence of electron effect on the hydrolysis kinetics of a
the dynamic hydrazone bond at high pH,18 or reduction of the HUB, we selected 1 (Fig. 1) as the model compound considering
dynamic olefin, alkyne and imine19 bonds. Thus, new dynamic that its dimethylamino group would change from a weak
covalent reactions with facile stabilizing strategies are of great electron donating group to a strong electron withdrawing group
interest and importance.
when the pH drops from neutral to acidic. To assess the
Polyurea is one of the most widely used industrial materials difference, 1 was dissolved in D2O and the hydrolysis profile
for coating because it features multiple advantages such as was monitored by 1H NMR with or without addition of DCl. For
high strength and toughness, and high thermal and chemical 1 with the addition of DCl, we observed the appearance of a new
stability.20 Despite these superior properties, advancements in
chemistry and applications are quite limited. Recently our
group developed the hindered urea chemistry where the bulky
a Department of Materials Science and Engineering, University of Illinois at Urbana-
Champaign, Urbana, Illinois 61801, USA. E-mail: jianjunc@illinois.edu
b School of Materials Science and Engineering, Henan University of Technology,
100 Lianhua St, Zhongyuan District, Zhengzhou, Henan, China
Scheme 1 Illustration for the acid-assisted de-tert-butylation of
a
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
hindered urea bond.
d1cc00715g
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Fig. 2 (a) Structures of the different hindered urea compounds used to
confirm the feasibility of the de-tert-butylation reaction. (b) Hindered urea
structures bearing N-adamantyl substituent can also be stabilized by acid.
Fig. 1 1H NMR spectra of compound 1 in D2O (i) shortly after adding DCl
(2 mL in 600 mL D2O); (ii) 2 h after adding acid; (iii) with further addition of
compound 2 after acid treatment.
de-tert-butylation reaction. Four solutions of 1 were prepared
with citrate buffer of pH 3, 4, 5, and 6, and the de-tert-
butylation process of 1 at different pH was monitored by
HPLC (Fig. S27, ESI†). It was observed that the hydrolysis
product predominated at higher pH and the de-tert-butylated
species only emerged at pH 3. This result indicates that high
acidity is necessary for the de-tert-butylation reaction. We
also studied the reaction kinetics with different urea and acid
concentrations. As shown in Fig. 3a, a model reaction was
chosen at either fixed acid concentration (50 mM) with the
variation of the urea concentration (Fig. 3b) or fixed urea
concentration (0.5 mM) with the variation of the acid concen-
tration (Fig. 3c). A first order correlation to both the urea and
acid concentration was observed, which explains why there
was almost no hydrolyzed product observed in Fig. 1-ii. As
shown in Fig. 3d, the dissociation (k-1) and de-tert-butylation
(kdt) are two competing processes. The former is acid
independent30 while the latter accelerates with increased
set of peaks (Fig. 1-i, red peaks) in addition to 1 (Fig. 1-i, black
peaks). Compound
1 completely disappeared after 2 h
1
(Fig. 1-ii). However much to our surprise, the H NMR of the
products in the neutral and acidic groups was different. To
further confirm this, compound 2, which was a hydrolysis
product, was added to the acidic group (Fig. 1-iii). The new
set of peaks did not coincide with that of compound 2 (Fig. 1-iii,
blue peaks), implying a degradation process different from
hydrolysis. MS analysis showed that the acid-induced reaction
of 1 resulted in 3, the tert-butyl group depleted form of 1
instead of the hydrolysed product (2).
We next explored if the de-tert-butylation is generally applic-
able in hindered urea compounds. Different tert-butyl based
hindered ureas prepared from either aliphatic or aromatic
isocyanates and tert-butyl amines (Fig. 2a and Scheme S1,
Fig. S1–S10, ESI†) were tested in either D2O or CDCl3, with
either DCl or methanesulfonic acid/trifluoroacetic acid added,
respectively. The products were confirmed by NMR and MS
(Fig. S13–S23, ESI†). All compounds showed very fast and
exclusive de-tert-butylation with barely any hydrolysis product
observed. These results demonstrated that the acid assisted
de-tert-butylation reaction was achievable in a wide range of
compounds bearing hindered urea bonds in both aqueous and
organic solvents with added inorganic/organic acids. What’s
more, excessive acid would not cause degradation of the urea
linkage under our experimental conditions. We also tested two
urea compounds bearing an N-adamantyl substituent (Fig. S11
and S12, ESI†). With no surprise, the adamantyl group can also
be readily removed by acid (Fig. 2b and Fig. S24–S26, ESI†),
implying that any substituents on the HUB that can form a
stable tertiary carbocation upon acidification would undergo a
similar depletion process, resulting in a stable urea structure.
To have a better understanding of the role acid plays in
Fig. 3 (a) Scheme for the model reaction. (b) The relationship between
reaction rate and urea concentration (acid concentration: 50 mM). (c) The
relationship between reaction rate and acid concentration (urea concen-
tration: 0.5 mM). (d) Illustration of the relationship between dissociation
the reaction, 1 was used to study the pH dependence of the and de-tert-butylation.
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acid concentration. When subject to high acidity, the de-tert- backbones. We also studied the acid-induced de-tert-butylation
butylation would be much faster than the dissociation process. reaction in aromatic HUPs, which gave similar results (Fig. S36,
Once de-tert-butylated, the hindered urea concentration would ESI†).
decrease, further reversing the dissociation reaction towards the
We then went on to explore the de-tert-butylation reaction in
formation of hindered urea, which explained why only de-tert- a crosslinked organogel. G1, a model HUB containing cross-
butylated species were observed at high concentration of acid. For linked polymer, was synthesized at the TEA : TEG : DtBEA :
aromatic HUB compounds with much greater dissociation HMDI ratio of 1 : 6.5 : 4 : 12 in 30 wt% DMF (Fig. 5a). Half of
constants, higher concentration of acid was required to drive the gel was treated with methanesulfonic acid in CHCl3 for 1 h
the de-tert-butylation process and prevent the formation of hydro- and then washed with CHCl3 three times to remove acid (G1-H).
lyzed species (Fig. S22 and S23, ESI†).
G1-H was then immersed in CHCl3 overnight to ensure further
After studying the reaction in small molecules, we went on removal of the acid. The washed G1-H and G1 were immersed
to study the feasibility of the de-tert-butylation chemistry in in CHCl3, and then incubated with an excessive amount of
linear hindered urea polymers (HUPs) using P1 (Fig. 4a) as the amine. The acid treated gel G1-H remained structurally intact
model polymer. Poly(propylene glycol) was added to increase while the gel G1 was completely dissolved (Fig. 5b), demon-
the solubility of the de-tert-butylated polymer. The NMR studies strating that acid treatment can efficiently stabilize the gel
revealed complete removal of the tert-butyl group with acid bearing dynamic HUB presumably due to the acid-induced
treatment of P1 (Fig. 4b). To assess the effectiveness of the de-tert-butylation.
de-tert-butylation reaction, both the original (P1) and acid-
To further demonstrate the acid-induced de-tert-butylation
treated polymers (P1-H) were incubated in amine solution in HUB containing materials, thin films were made from G1
and then characterized by GPC. The hindered urea bond in and the mechanical properties of the films were analyzed pre-
P1 will dissociate giving an isocyanate intermediate, which will and post-acid treatment. As shown in Fig. 5c, the Young’s
then be trapped by free amine, leading to degradation of the modulus of the gel increased by one order of magnitude after
urea backbone and thus decrease of the MW (Fig. 4a, pink acid treatment. The acid-treated material also showed much
highlight). However P1-H contains only regular urea bonds, improved creep resistance (Fig. 5d) and negligible stress relaxa-
which are stable towards free amine. Thus the urea backbone tion (Fig. 5e). We attributed these observations to the increased
will remain intact. As shown in Fig. 4c, the GPC curve of P1-H number of hydrogen-bonding motifs (regular urea bond) after
matched well with that of P1, showing that acid treatment did de-tert-butylation and therefore stronger bond strength in the
not cleave the backbone of the polymer. After incubation with acid-treated materials. These experiments clearly show that the
amine, as expected, P1 showed a significant molecular weight de-tert-butylation reaction works very well in both gel and solid
decrease (the P1-amine blue curve, Fig. 4c), while the MW of HUB-containing materials and can efficiently stabilize the urea
P1-H did not change after the amine treatment (the P1-H-amine bonds by removing the dynamicity of the HUB and thus
green curve, Fig. 4c). These experiments demonstrated the high improve the mechanical property of the materials.
efficiency of the de-tert-butylation reaction in HUPs and
its utility in stabilizing the HUPs without degrading their
Fig. 5 (a) Preparation of the HUB containing organogel in 30 wt% DMF
(TEA : TEG : DtBEA : HMDI = 1 : 6.5 : 4 : 12). (b) G1 and G1-H (acid-treated
Fig. 4 (a) De-tert-butylation of P1 and amine treatment of P1 and P1-H,
the de-tert-butylated P1. (b) Partial 1H NMR spectra of P1 and P1-H.
(c) GPC overlay of P1, P1-H, P1-H-amine, and P1-H-amine.
G1) after incubation with amine overnight in CHCl3. (c) Stress–strain curve
of G1 and G1-H thin film. (d) Creep behavior of G1 and G1-H thin film.
(e) Stress relaxation of G1 and G1-H thin film.
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Conflicts of interest
There are no conflicts to declare.
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