The performance of phthalimide-N-oxyl anion

Article abstract of DOI:10.1007/s00706-006-0553-6

Alkali metal salts of phthalimide-N-oxyl, including Li, Na, and K were prepared and applied as novel selective catalysts to promote the cyclotrimerization of aryl and alkyl isocyanates. This paper is addressing these salts as a new class of organic nucleo

Full text of DOI:10.1007/s00706-006-0553-6

Monatshefte f€ur Chemie 137, 1591–1595 (2006)
DOI 10.1007/s00706-006-0553-6
Short Communication
The Performance of Phthalimide-N-oxyl
Anion
Mohammad G. Dekamin1;ꢀ, Firouz M. Moghaddam2,
Hamdollah Saeidian2, and Shadpour Mallakpour3
1
Organic Chemistry Research Laboratory, College of Chemistry, Iran University
of Science and Technology, Tehran, Iran
2
Department of Chemistry, Sharif University of Technology, Tehran, Iran
3
Organic Polymer Chemistry Research Laboratory, College of Chemistry,
Isfahan University of Technology, Isfahan, Iran
Received May 20, 2006; accepted June 8, 2006
Published online November 30, 2006 # Springer-Verlag 2006
Summary. Alkali metal salts of phthalimide-N-oxyl, including Li, Na, and K were prepared and
applied as novel selective catalysts to promote the cyclotrimerization of aryl and alkyl isocyanates.
This paper is addressing these salts as a new class of organic nucleophilic catalysts.
Keywords. Nucleophilic organocatalyst; Isocyanates; Potassium phthalimide-N-oxyl; Heterocycles.
Introduction
Designing of new specific catalysts and exploring their catalytic activity has
caused profound effects in optimizing the efficiency of a wide range of organic
transformations [1]. Development of such catalysts has resulted in more eco-
nomical and environmentally friendly chemistry through replacing nonselective,
unstable, toxic, or flammable catalysts [1, 2]. In this context, nucleophilic organo-
catalysts have achieved an outstanding place to promote many important organic
reactions in recent years [1]. Among these catalytic systems, stable N-heterocyclic
carbenes [3, 4] and proazaphosphatrane or its derivatives [5, 6] could be men-
tioned, which were developed in the recent two decades as phosphine mimics or
counterparts.
Cyclotrimerization of isocyanates is one of the reactions which have been in-
vestigated with regard to efficient nucleophilic organocatalysts at the threshold
of their application in organic synthesis [7, 8]. Isocyanates are very useful and
ꢀ
Corresponding author. E-mail: mdekamin@iust.ac.ir

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M. G. Dekamin et al.
reactive substrates undergoing different reactions including conversion to carbodiim-
ide, allophonate, urea, trimer, and dimer. Therefore, developing of catalysts which
promote cyclotrimerization selectively is of great importance owing to its applica-
tion in polymer industry [9, 10]. This arises from the significant effects of isocya-
nurate structure on the properties of the resulting polymers such as polyurethanes
or polyureas [10, 11]. On the other hand, the resulting aromatic isocyanurate
structure has unique properties such as rigidity, high symmetry, and low-toxicity,
which have led recently to its applications in selective ion bonding, chiral discrim-
ination, and medicinal chemistry [11, 12].
A part of our ongoing research is directed toward new readily available organic
[11] and inorganic [13] nucleophilic catalysts for cyclotrimerization of aryl and
alkyl isocyanates. Here we wish to report the first use of phthalimide-N-oxyl alkali-
metal salts as selective nucleophilic organocatalysts for the cyclotrimerization of
aryl and alkyl isocyanates under mild and solvent-free conditions.
Results and Discussions
Since N-hydroxyphthalimide (1) has a pKa of 6.1, alkali-metal salts of 1, including
the potassium (2), sodium (3), and lithium (4) salts, could be readily prepared
by adding 1 to a saturated solution of their corresponding hydroxides in EtOH
(Scheme 1). Quantitative yields were obtained in all cases (cf. Ref. [14]).
The catalyst 2 demonstrated proper activity and solubility for the cyclization
of phenyl isocyanate (5a), as model compound, under solvent-free conditions
(Scheme 1).
Thus, upon heating a mixture of 5a with only 0.05 mol% of 2, 95% of the
cyclotrimerization product, 1,3,5-triphenyl-1,3,5-triazine-2,4,6(1H,3H,5H)-trione
(triphenyl isocyanurate, 6a) [11], was selectively obtained at 70ꢁC within 17 min.
Scheme 1

The Performance of Phthalimide-N-oxyl Anion
1593
To optimize the reaction conditions, various factors, such as the effect of differ-
ent mol% of the catalyst, temperature, and safer non-reactive solvent [8] were
investigated.
Applying higher mol% of 2 decreased the required reaction time while a
trace amount of dimer 7a, as the kinetically controlled product, was formed at
>0.2 mol% [7, 8]. The reaction time was also decreased by applying higher tem-
peratures which in turn prefer formation of trimer, as the thermodynamically con-
trolled product. On the other hand, the desired product 6a was obtained within
fewer minutes by using an equivalent amount of a tetraalkylammonium halide
(QX) at 70ꢁC. Formation of the dimer or substantial loss of yield was not observed
under this situation. Therefore, diverse QXs, in terms of both halide and ammo-
nium part size, were also investigated. Accordingly, tetraethylammonium bromide
(TEAB) showed proper activity with slightly improving the yield. These results led
us to perform the reaction at ambient temperature. In this situation a quantitative
yield of the product was obtained. The significant advantage of the solvent-free
conditions was noticed when the reaction was performed in dry toluene in the
presence of TEAB. Under this situation, a lower yield and prolonged reaction time
was observed. Also, 3 and 4 as counterparts of 2, but with tighter cations were in-
vestigated at the optimized condition. These salts displayed their catalytic activity
only in the presence of QX.
Other aryl isocyanates at optimized reaction condition (0.1 mol% 2, 70ꢁC)
behaved properly. The applied temperature facilitated the reaction of solid sub-
strates under solvent-free conditions (e.g. 5d and 5e, which melt below this tem-
perature; Table 1).
Although, the so far introduced catalysts generally promote cyclization of phe-
nyl isocyanate they do not efficiently catalyze the reaction of alkyl isocyanates
displaying steric hindrance or even aryl isocyanates containing electron releasing
groups. Therefore, exploring more effective catalysts for this purpose is a matter of
challenge yet [8, 11]. In our hands, 4-methoxyphenyl isocyanate (5b) at optimal
reaction conditions produced 86% of its corresponding isocyanurate 6b within
17 min. 1-Naphthyl isocyanate (5c), which reacted by previous protocols after a
rather long time, afforded 80% of its trimer 6c in just 78 min [11]. On the other
Table 1. Cyclotrimerization of aryl and alkyl isocyanates at optimized conditions
Isolated
yield=%a
Entry
Substrate
R
Time=min
Trimer
1
2
3
4
5
6b
7
8
5a
5b
5c
5d
5e
5f
Phenyl
4-Methoxyphenyl
1-Naphthyl
7
17
6a
6b
6c
6d
6e
6f
97
86
80
93
97
82
78
48
78
4-Chlorophenyl
3,4-Dichlorophenyl
Ethyl
6
4
150
240
240
5g
5h
Butyl
6g
6h
Cyclohexyl
a
b
Average of at least two runs; reaction was run at 50ꢁC, below substrate boiling point

1594
M. G. Dekamin et al.
hand, aryl isocyanates containing electron withdrawing substituents, such as 5d
and 5e, displayed even shorter reaction times. In general, the yields for cyclization
of aryl isocyanates are good to quantitative. Alkyl isocyantes which could be
cyclized only by a few catalysts afforded their respective isocyanurates in good
yields using the novel catalyst system. However, the required reaction time is
longer than for aryl isocyanates (Table 1, entries 6–8). It is noteworthy that the
lower reactivity of cyclohexyl isocyanate (5h) seems to be related to its steric
hindrance [8, 11a] as compared to 5f or 5g. Furthermore, it should be noted that
preparation and storage of the catalyst is very convenient comparing to other
catalysts [7, 8].
In conclusion, the catalytic performance of the alkali metal salts 2–4 as readily
prepared and stored organonucleophilic catalysts for the cyclotrimerization of iso-
cyanates was investigated for the first time. The catalytic performance of 2 is
superior or comparable to the most efficient catalytic systems introduced so far.
An easy and solvent-free route to prepare diverse and challenging isocyanurates at
high to quantitative yields is thus established.
Experimental
All yields refer to the isolated ones based on an average of at least two runs. All reactions were
protected from air moisture using a CaCl2 tube. FT IR spectra were recorded as KBr pellets on a
Nicolet Magna 550 spectrometer. A Bruker DRX-500 Avance (500MHz) spectrometer was used to
1
record the H NMR spectra. All NMR spectra were determined in CDCl3 or acetone-d6 at ambient
temperature. Chemical shifts (ꢀ) were expressed in ppm relative to TMS (ꢀ ¼ 0.00) and J values are
given in Hz. GC-MS spectra were recorded on a HP 6890-HP 5973. Melting points were determined
€
on a Buchi B540 apparatus. Analytical TLC was carried out using Fluka 0.2 mm silica gel 60 F-254
Al-plates. All substrates were purchased from Fluka or Merck and used as received except 5b. This
latter was synthesized according to Ref. [11]. After distillation, it was stored under dry condition. Dry
ether was freshly distilled over Na and benzophenone.
General Procedure for Preparation of Phthalimide-N-oxyl Salts 2–4
To 1.00g 1 (6.13 mol) dissolved in 20cm3 absolute EtOH an equivalent amount of KOH, NaOH, or
LiOH was added. The mixture was refluxed, cooled, and the obtained precipitate was filtered. It was
then washed with additional 10 cm3 absolute EtOH. The yields were quantitative and the salts were
dried under vacuum for 2 h at 70ꢁC prior to use. 1H NMR (500 MHz, D2O): ꢀ ¼ 7.45–7.31 (m, 4H); IR
(KBr): ꢁꢀ¼ 3057, 1756, 1662, 1179, 1022, 992, 691 cmꢂ1
.
General Procedure for Cyclotrimerization of Isocyanates
The procedure was identical to the one described in Refs. [11, 13] using 0.1 mol% 2 at 70ꢁC. All of the
products 6a–6h are known and their physical constants and spectroscopic data were in agreement with
their structures as described in Refs. [7, 8, 11].
Acknowledgements
M.G.D. gratefully acknowledges the Research Council of Iran University of Science and Technology
(IUST), Iran, for financial support of this research.

The Performance of Phthalimide-N-oxyl Anion
1595
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