Scheme 2
Scheme 3
chemicals,23,24 spiroorthocarbonate 4 is formed here from
environmentally benign raw materials. It may arise from an
open carbonate of TMP, via a monocyclic intermediate
(Scheme 3), which under the highly polar conditions might
lose its center carbon hydroxyl in an SN1-type process. A
stabilised cation would result, and on ring-closure, spiroor-
thocarbonate 4 is formed.
Toxicological Characterisation. The primary skin ir-
ritation effect of TMPO was investigated according to the
method recommended by OECD.25 Rabbits were exposed
to the article at two skin sites on their back. After 4 h of
exposure the test article was removed and the skin examined
from 1 to 72 h after termination of exposure. No or very
slight skin reactions were observed in all animals during the
examination period. According to the directive of the
Commission 93/21/EEC (April 27, 1993), TMPO should not
be classified as a skin irritant. Also, the eye irritant effect of
TMPO was investigated according to official recommenda-
tions.26 One albino rabbit was exposed to 0.1 mL of the test
article in the left eye. The eye was examined from 1 h to 14
days after dosing. Marked signs of corneal and conjunctival
irritation were observed on early observations. On day 14,
no abnormalities were observed in the rabbit. According to
the same directive as above, TMPO should be classified as
eye irritating.
declining levels of TMP and urea. The level of biuret during
the sampling period was very low (<1%). Triuret could not
be analysed, and cyanuric acid was not detected.
In the subsequent step, the pyrolysis (195-215 °C, 10-
50 mmHg), crude TMPO was collected continuously by
distillation from heavier constituents. Running the pyrolysis
at temperatures above ca. 220 °C should be avoided due to
possible decomposition of the components in the reaction
mixture.21
Some white solid always deposited in the cooler, but most
of this material was found in the cooling traps. When running
the process in the pilot plant, steam was flushed through the
column and cooler at intervals to prevent clogging. The solid
was shown to be ammonium carbamate (IR). Ammonium
cyanate,20 which was suspected to be present, could not be
detected. The solid lost carbon dioxide and ammonia on
heating (TGA-IR). In neither case was any cyanate signal
found. The amount of this solid material corresponded to
40-50% of the nitrogen content of urea.
The same yields and selectivities as those given in Table
2 were found on a 6-fold scale-up (120 g of urea). However,
in the pilot plant (ca. 50 kg of urea, TMP/urea ) 1.47) the
yield of TMPO declined (32% based on urea).
Conclusions
Besides TMP (1), the residue after separation of TMPO
(2) contained spiroorthocarbonate 4 and small amounts of
di-TMP (3).22 Data from lab-scale experiments suggested
formation of 4 to be promoted at a lower TMP/urea ratio.
Its presence was indicated by TLC and 1H NMR even after
transcarbonylation at low temperature (120 °C, 14 h).
According to size-exclusion chromatography, there was no
build-up of polymeric species during pyrolysis either (“peak
Mw” e 250). The intermediacy of carbonate 5 remains
uncertain (Scheme 2).
This report summarises a novel route to 3-ethyl-3-
(hydroxymethyl)oxetane. The approach uses inexpensive,
widely available starting materials, urea and trimethylolpro-
pane, and provides some mechanistic insights. This chemistry
can be performed on a multikilogram scale and avoids use
of environmentally malign chemicals. Toxicological screen-
ing revealed 3-ethyl-3-(hydroxymethyl)oxetane to be irritat-
ing to eye but not to skin.
Experimental Section
The spiroorthocarbonate 4 deserves further comments,
since it could constitute a valuable by-product. Spiroortho-
carbonates are known to polymerise with low volume
reduction, which may have profound influence on adhesion
and other properties of coatings.23 Ring-opening polymeri-
sations of such compounds can even occur with expansion
in volume.23a Compared to previously published methods of
preparation, which often rely on the use of toxic or corrosive
Materials. Urea (Svenska Foder), trimethylolpropane (1),
and ditrimethylolpropane (3) (Perstorp Specialty Chemicals),
5-ethyl-5-hydroxymethyl-1,3-dioxan-2-one (5) (Synthelec
AB, S-223 70 Lund), 46% sodium hydroxide (Norsk Hydro),
biuret and cyanuric acid (Fluka), and ammonium carbamate
(Aldrich) were used as received. An analytical sample of
3,9-diethyl-3,9-dihydroxymethyl-1,5,7,11-tetraoxaspiro[5,5]-
undecane (4) was obtained by chromatographic purification
of pyrolysis residues.
(21) (a) Barto´k, M.; Molna´r, A.; Barto´k-Bozoki, G. Acta Chim. Hungar. 1983,
114, 375. (b) Halary, J. L.; Yvernault, T.; Casteignau, G. Bull. Soc. Chim.
Fr. 1972, 4655. (c) Jaubert, M.; Mazet, M.; Yvernault, Y. Bull. Soc. Chim.
Fr. 1974, 595
(22) Under similar conditions pentaerythritol and urea are claimed to yield some
dipentaerythritol and bis-3,3-(hydroxymethyl)oxetane, see ref 16.
(23) (a) Bailey, W. J.; Sun, R. L.; Katsuki, H.; Endo, T.; Iwama, H.; Tsushima,
R.; Saigou, K.; Bitritto, M. M. ACS Symp. Series (Ring-Opening Polym.)
1977, 59, 38, (b) Lam, P. W. K.; Piggott, M. R. J. Mater. Sci. 1989, 24,
4069, (c) Chappelow, C. C.; Eick, J. D.; Pinzino, C. S. U.S. Patent 5,808,-
108, 1998; Chem. Abstr. 1998, 129, 246078.
(24) (a) DeWolfe, R. H. Synthesis 1974, 153, (b) Kantlehner, W.; Funke, B.;
Haug, E.; Speh, P.; Kienitz, L.; Maier, T. Synthesis 1977, 73, (c) Mues, P.;
Buysch, H.-J. Synthesis 1990, 249.
(25) (a) Acute Dermal irritation/Corrosion. OECD Guidline No. 404, EEC, 1992.
(b) Acute Toxicity (skin irritation). Guidline B.4, 29.12.1992, Scantox:
Denmark, 1992.
(26) (a) Acute Eye Irritation/Corrosion. OECD Guideline No. 405, Feb. 1987.
(b) Acute Toxicity (Eye irritation). EEC, No. L 383A/127:29.12.1992, B.5,
Scantox: Denmark, 1992.
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