Highly efficient cyclotrimerization of isocyanates using N-heterocyclic olefins under bulk conditions

Article abstract of DOI:10.1039/c9cc06402h

With a catalyst loading as low as 0.005%, high to excellent yields of isocyanurates could be achieved from N-heterocyclic olefin mediated organocatalytic cyclotrimerization of a wide range of isocyanates under bulk conditions. Experimental details coupled with structural characterization of the key intermediates led to comprehensive mechanistic studies of cyclotrimerization.

Full text of DOI:10.1039/c9cc06402h

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Highly efficient cyclotrimerization of isocyanates
using N-heterocyclic olefins under bulk
conditions†
Cite this: Chem. Commun., 2019,
55, 12563
Received 18th August 2019,
Accepted 23rd September 2019
Chengkai Li,‡ Wuchao Zhao,‡ Jianghua He and Yuetao Zhang
*
DOI: 10.1039/c9cc06402h
rsc.li/chemcomm
With a catalyst loading as low as 0.005%, high to excellent yields several unaddressed key issues existing in the cyclotrimerization
of isocyanurates could be achieved from N-heterocyclic olefin of isocyanates. First, it is inevitable to yield a dimer, allophanate,
mediated organocatalytic cyclotrimerization of a wide range of urethane or carbodiimide along with the production of a trimer
isocyanates under bulk conditions. Experimental details coupled due to poor selectivity.1,11,26 Second, there is no structural
with structural characterization of the key intermediates led to characterization of the key reaction intermediate species yet.
comprehensive mechanistic studies of cyclotrimerization.
Third, a highly efficient catalyst system needs to be developed.11
To this end, this contribution reports the employment of strong
In recent years, 1,3,5-triazinane-2,4,6-triones (isocyanurates) nucleophilic N-heterocyclic olefins (NHOs) as organocatalysts to
bearing stable six-membered rings have attracted intense atten- achieve highly efficient synthesis of isocyanurates from the cyclo-
tion since they could be employed as additives to achieve trimerization of a wide range of isocyanate substrates under
enhanced performance of polyurethane foams, coating materials solvent-free conditions at room temperature (RT), with a catalyst
and composites1 and polymers2,3 due to their intriguing proper- loading as low as 0.005 mol%.
ties of excellent rigidity, high thermal stability and hydrolytic
As highly polarized molecules with an electron-rich exocyclic
stability. Their derivatives are also utilized in the application of CQC double bond, NHOs could serve as ligands to stabilize
chiral discrimination,4 selective ion bonding,5 medicine,6,7 and metals or organocatalysts in the preparation of polyesters,
cross-linker8 and periodic mesoporous organosilica.9 Cyclotrimer- polyethers, and polyacrylates as well as in organic synthesis.27–37
ization of isocyanates provides a facile strategy to readily achieve Previous studies indicated that the substituents on the exocyclic
the synthesis of isocyanurates.1,10,11 Metal-containing complexes carbon atom of NHO have a great influence on the polymerization
based on Yb, Eu, Sm, Nb, Sn, Pd, Mn, Fe, Na, and Li are reported activity.32,36,38 NHO1–3 bearing different substituents on the
as pre-catalysts for the cyclotrimerization of isocyanates.12–16 exocyclic CQC double bond were synthesized and their efficacies
However, most of them are only applicable for either aryl iso- on the cyclotrimerization of a wide range of isocyanates as
cyanates or alkyl isocyanates.13,14,16,17 Recently, catalyst systems substrates were examined (Scheme 1).31,38,39 It turned out that
composed of organic Lewis bases have demonstrated their once NHO1 having two hydrogen atoms on the exocyclic CQC
application in different reactions.17–21 Louie et al. discovered double bond was added to phenyl isocyanate (1) in toluene at RT,
that N-heterocyclic carbines can serve as highly efficient organo- the reaction mixture immediately turned from orange to colour-
catalysts for the cyclotrimerization of isocyanates, affording up to less, but no trimer product was observed up to 24 h (run 1, Table
99% yield of trimer products in an hour.11 Several organocatalysts S1, ESI†). To gain more insights into the reaction, we performed
such as tetrabutylammonium phthalimide-N-oxyl, tetraethyl- an in situ NMR reaction and found that 2 equiv. of 3-methylphenyl
ammonium 2-(carbamoyl)benzoate, ketene cyclic N,O-acetal and isocyanate (3) reacted with NHO1 to yield an addition product
tetrakis(dimethylamino)ethylene are also found to be active for INT13 (Fig. S1 and S2, ESI†). Therefore, a possible reaction path-
the cyclotrimerization of isocyanates.22–25 So far, there are still way was proposed for the reaction as shown in Scheme S1 (ESI†),
in which, the reaction of NHO1 with 3 produced a zwitterionic
State Key Laboratory of Supramolecular Structure and Materials,
College of Chemistry, Jilin University, Changchun, Jilin 130012, China.
E-mail: ytzhang2009@jlu.edu.cn
intermediate A. The subsequent H transfer from the methylene to
the carbamoyl anion of the intermediate A generated intermediate
B, which went through continuous nucleophilic attack and a
H-transfer reaction to form INT13. This is similar to what is
proposed for the cyclotrimerization of isocyanates catalyzed using
N,N0-dimethyl cyclic ketene, N,N0-acetals or N-methyl cyclic
† Electronic supplementary information (ESI) available. CCDC 1947755. For ESI
and crystallographic data in CIF or other electronic format see DOI: 10.1039/
c9cc06402h
‡ Contributed equally.
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achieving quantitative monomer conversion within three minutes
and a high to excellent product yield (up to 97%) (runs 3 to 8,
Table S2, ESI†). It is noted that isocyanates 2 and 4 having a
substituent at the ortho position exhibited relatively lower activity
than other substrates, probably because the substituent at the
ortho position hindered the nucleophilic attack of the incoming
isocyanate by the anionic centre (vide infra). Similar results were
observed for the Fe and Mn complex-catalyzed cyclotrimerization
of secondary and tertiary aliphatic isocyanates.16 NHO3 is also
effective for the cyclotrimerization of aliphatic isocyanate 12,
furnishing the corresponding trimer 12a in 90% yield (run 13,
Table S2, ESI†). This might be attributed to the higher electron
cloud density at the carbon of isocyano in aliphatic isocyanates
than that in aromatic isocyanates, which was not conducive to
nucleophilic attack and the formation of a stable zwitterionic
intermediate (vide infra). Previously, Dekamin and co-workers also
found that Lewis bases are less active for the cyclotrimerization of
aliphatic isocyanates than they are for aromatic isocyanates.22 We
also compared the effectiveness of NHO with the other commonly
used, strong organic bases, such as 1,8-diazabicyclo(5.4.0)-
undec-7-ene (DBU) and 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-
Scheme 1 Structures of NHOs and isocyanates employed in the cyclo-
trimerization of isocyanates.
ketene-N,X (X = S, O)-acetals, with no observation of a spiro 5-ene (MTBD), on the cyclotrimerization of 1. It turns out that
compound.24,40 Compared with NHO1, INT13 showed a larger DBU did not produce any cyclotrimerization product for up to
steric hindrance that led to its incapability of reacting with 48 h whereas MTBD could furnish around 80% yield of the
isocyanates (run 1, Table S3, ESI†), which also well explains why cyclotrimerization product after 3 h (runs 14 and 15, Table S2, ESI†).
NHO1 possessing two H atoms on the exocyclic carbon is
The cyclotrimerization of isocyanate was also performed
ineffective for cyclotrimerization of isocyanates. Previous studies under bulk conditions with 0.1 mol% catalyst loading of
revealed that NHOs with similar structures also exhibited poor NHO3, by adding the isocyanate into a vial containing prede-
activity towards the polymerization of acrylic monomers owing termined amounts of NHO3. Owning to its high efficiency,
to the occurrence of the H transfer reaction.36 To verify our NHO3 would be wrapped inside the product and loses its
assumption, we employed NHO2 bearing one H atom and one activity upon coming into contact with the isocyanate. There-
methyl group on the exocyclic carbon to examine the reaction. The fore, we employed a stock solution of NHO3 dissolved in 100 mL
stoichiometric in situ NMR reaction of isocyanate 3 with NHO2 in toluene to examine the subsequent reactions, achieving a
a 1 : 1 ratio generated a single addition product INT23 (Scheme S2 similar high to excellent product yield of aromatic isocyanurates
and Fig. S3, S4, ESI†), which could be successfully isolated and but a much higher polymerization activity (Table 1) than that
utilized for the cyclotrimerization of isocyanates. Interestingly, the obtained for cyclotrimerization performed in toluene (Table S2,
isocyanates 1, 3, and 5 could be quantitatively converted into the ESI†). Even a 0.005% catalyst loading of NHO3 can nearly quanti-
corresponding trimer products within several minutes (run 2–4, tatively transform 20 000 equiv. of isocyanate 1 into a trimer with
Table S3, ESI†), indicating that INT23 is highly effective for the 98% isolated yield within 3 minutes (run 2, Table 1). Enhanced
reaction. To our expectations, similar reactivity and product yields polymerization activities were also observed for the cyclotrimeriza-
could be obtained for the cyclotrimerization of 1, 3, and 5 by using tion of other aromatic and aliphatic isocyanates performed under
NHO2 as an organocatalyst (run 3–5, Table S1, ESI†).
bulk conditions. We also observed a similar trend that aliphatic
Since the H transfer reaction that leads to the deactivation isocyanates showed lower polymerization activity than aromatic
of the catalyst accounted for the ineffective polymerization of isocyanates (runs 11–14 vs. runs 1–10, Table 1).
polar vinyl monomers catalyzed using NHOs,36 we chose NHO3
There are mechanistic studies on the cyclotrimerization of
having two methyl groups on exocyclic carbon for the reaction. isocyanates catalyzed using Lewis bases reported by other
Isocyanate 1 could be nearly quantitatively converted to iso- research groups, but experimental evidence is still lacking.
cyanurates 1a in 97% isolated yield when the reaction was Therefore, we performed a series of in situ NMR reactions to
performed in toluene with a 1 mol% catalyst loading of NHO3 gain more insights into the reaction. First, the reaction of NHO3
(run 1, Table S2, ESI†) whereas a 98% isolated yield was with isocyanates 1 in 1 : 10 ratio afforded the cyclotrimer 1a and a
obtained with an even lower catalyst loading of 0.04 mol% zwitterionic species INT31 in a 3 : 1 ratio, without the observation
(run 2, Table S2, ESI†). It is noted that we did not observe a of free NHO3 (Fig. S9, ESI†). Second, the stoichiometric in situ
dimeric product, a common by-product found in the reaction.1,11 It NMR reactions of NHO3 with isocyanates 1, 3, and 9 in a 1 : 1 ratio
turned out that NHO3 showed high activity towards the cyclo- cleanly yielded the corresponding zwitterionic species INT31,
trimerization of a wide range of aromatic isocyanates possessing INT33 and INT39, respectively, indicating that these zwitterionic
either an electron donating or electron withdrawing substituent, species were readily formed and fairly stable (Fig. S5–S8, ESI†).
12564 | Chem. Commun., 2019, 55, 12563--12566
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Table 1 NHO catalyzed the cyclotrimerization of isocyanatesa
Run
RNCO
RNCO:NHO3
Time (min)
Productb
Yieldc (%)
1
2
3
4
5
6
7
8
1
1
2
3
4
5
6
7
1000
20 000
1000
1000
1000
1000
1000
1000
1000
200
1000
1000
1000
1000
o1
o3
120
o2
180
o2
3
1a
1a
2a
3a
4a
5a
6a
7a
95
98
90
96
91
97
97
96
96
98
95
88
89
88
o1
9
8
3
8a
Scheme 2 Reaction mechanism proposed for NHO3 catalyzed the cyclo-
trimerization of isocyanates.
10
11
12
13
14
10
11
12
13
14
1
10a
11a
12a
13a
14a
24 h
48 h
48 h
48 h
atom of –NCO of the first isocyanate to generate a trimer
through cyclization, along with the release of NHO3 for the
next catalytic cycle (Scheme 2). In path b (Scheme S3, ESI†), the
zwitterionic species generated from the reaction of NHO with
isocyanate could serve as the real catalyst to continuously attack
the next three incoming isocyanates and the resulting N anion
attacks the carbon atom of –NCO of the first isocyanate generating
a trimer through the cyclization and release the active zwitterionic
species for the next catalytic cycle.
Thanks to the stability of these zwitterionic species, it
enables us to employ them to perform the following control
experiments to verify the reaction pathway. It turned out that
INT39 could rapidly convert isocyanate 1 into 95% yield of 1a
within 2 min (1/INT39 = 200/1, run 5, Table S3, ESI†), indicating
that such zwitterionic species are the real active intermediates
for the cyclotrimerization of isocyanates. On the other hand,
the in situ NMR reaction of INT33 with isocyanate 1 in a 1 : 10
ratio clearly revealed the exclusive generation of INT31, without
the formation of INT33 (Fig. S10, ESI†), which suggested that
during the reaction, INT33 would release NHO3 to react with
a
Condition: carried out under bulk conditions, NHO3 dissolved in
b
c
100 mL toluene. Cyclotrimer product. Isolated yield.
We have successfully isolated INT39 generated from the reaction
of NHO3 and isocyanate 9 and characterized its structure by NMR
spectroscopy and X-ray crystallography (Fig. 1). Single crystal
structural data showed that the angles for O(1)–C(1)–C(2) and
N(1)–C(1)–C(2) are 131.601, 113.821, and 114.551, respectively, thus
furnishing a sum of 359.971. Moreover, the dihedral angle of O(1)–
C(1)–N(1) and O(1)–C(1)–C(2) is 1.321. These results indicated that
C(1) adopted sp2 hybridization. On the other hand, the bond
length for O(1)–C(1) is 1.256 Å, suggesting a double bond; the
bond length for N(1)–C(1) is 1.312 Å, which is close to that for the
double bond; and the bond length for C(1)–C(2) is 1.565 Å, which
is longer than that for the single bond, thus indicating that it
is easy for NHO3 to leave during cyclization. This information
revealed the presence of electron resonance around the C(1)
center and N(1) has a negative charge.
The above-mentioned results suggested two possible reaction
pathways (Scheme S3, ESI†): in path a, NHO3 nucleophilically
attacks the carbon atom of –NCO of isocyanate generating the
zwitterionic species INT, which will attack the second isocyanate
to form INT1. During the subsequent attack of the third
isocyanate by INT1, the resulting N anion attacks the carbon
isocyanate 1 to generate a new zwitterionic compound INT31
,
thus indicating that the zwitterionic INT33 was the real active
intermediate rather than the catalyst for the cyclotrimerization
of isocyanates. The above-mentioned discussion provided more
evidence to support that pathway a is more preferable for the
NHO-catalyzed cyclotrimerization of isocyanates (Scheme 2).
The cyclotrimerization of diisocyanates26,41 can also be
utilized to synthesize microporous polyisocyanurate materials
having potential applications in heterogeneous catalysis42 and
absorption of lipophilic compounds.43 With this highly
efficient NHO3 catalyst system for the cyclotrimerization of
isocyanates in hand, we further expanded the monomer scope
of this method by using three diisocyanates with different
distances between two –NCO groups as substrates (Scheme 1).
The observation of gel formation (Fig. S11, ESI†) indicated that
NHO3 transformed the diisocyanates into microporous polymer
networks (Scheme S4 and Table S4, ESI†). Compared with
the previous results,42,43 NHO3 exhibited higher polymerization
activity under mild conditions. Investigation of the properties and
Fig. 1 X-ray crystal structure of INT39. Hydrogen atoms and solvent mole-
cules are omitted for clarity, and ellipsoids are drawn at 50% probability.
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In summary, we represented the first example that strong
nucleophilic NHOs can serve as highly efficient organocatalysts
to achieve rapid cyclotrimerization of both aryl and alkyl
isocyanates into isocyanurates with high to excellent yields
under mild conditions and even higher polymerization activity
under bulk conditions. This NHO catalyst system exhibited
higher polymerization activity towards the cyclotrimerization
of aromatic isocyanates than for aliphatic isocyanates. We
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This work was supported by the National Natural Science
Foundation of China (Grant no. 21774042, 21871107 and 21975102).
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Conflicts of interest
The authors declare no competing financial interest.
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