Flash vacuum pyrolysis of oxazolidine-2,4-diones

Flash vacuum pyrolysis of four oxazolidine-2,4-diones 4 at 650–750 ˚ C leads to extrusion of CO 2 to afford α -lactams 10 (aziridinones) which fragment directly to give CO and an imine 12 but also rearrange to the isomeric iminooxiranes 11 which fragment to benzaldehyde and an isonitrile, isolated as the isomeric nitrile 15 . A new by-product in the formation of one of the oxazolidinediones is identified as the 3-hydroxyazetidine-2,4-dione 5 .


Introduction
Some time ago we reported that the readily available ethyl mandelate 1 could act as a convenient acyl anion equivalent by a sequence involving deprotonation, alkylation and flash vacuum pyrolysis (FVP) to afford phenyl ketones 2. 1 We later showed that the 1,3-dioxolan-4-one 3 could be used in the same way with the advantage that only one equivalent of base was required in this case.2As shown, both pyrolytic processes involve formation of an α-lactone which subsequently loses CO to afford the product.
In both thesestudies the range of electrophiles used was limited to alkyl halides.In an attempt to extend the scope of these methods we considered using other types of electrophile and in this paper we report that treatment of the dianion ethyl mandelate 1 with isocyanates leads to formation of 1,3-oxazolidine-2,4-diones which decompose in an unexpected way upon FVP to afford mixtures of imines, nitriles and benzaldehyde by way of intermediate α-lactams.

Results and Discussion
Reaction of ethyl mandelate with two equivalents of sodium hydride in THF followed by one equivalent of the appropriate isocyanate gave the expected oxazolidine-2,4-dione products 4 a-d in moderate yield.Formation of oxazolidine-2,4-diones from α-hydroxy esters and isocyanates under a variety of conditions is well known,3 and indeed 4a was first prepared in this way in 1898.4More recently both isothiocyanates5,6 and carbodiimides7 have been used to effect the same transformation.
Rather surprisingly preparation of 4a resulted in formation of a by-product which was readily identified by its spectroscopic data as the 3-hydroxyazetidine-2,4-dione 5 [δH 3.40 (1 H, br s, OH); δC 169.6 (C=O) and 54.9 (4ry)].Azetidine-2,4-diones, imides of malonic acid, are a rather little known class of heterocycles and following their first synthesis by Staudinger,8 they have been formed in a variety of ways.9-14However as far as we are aware the present synthesis represents a new method.The different mechanisms by which we believe the dianion (enediolate) 6 may react to give either 4 or 5 are shown below.In an attempt to divert the reaction entirely towards the formation of 5 we added one equivalent of Me3SiCl prior to the isocyanate.In fact this had the opposite effect and supressed formation of 5 completely, a result which we believe to be due to formation of 7 in which the C-acylation necessary to form 5 is blocked.As far as we are aware, the thermal decomposition of oxazolidine-2,4-diones has not been examined before.Comparison of the pyrolytic behaviour of similar systems shows that it can be difficult to predict the course of the fragmentation.15For example, while FVP of the 1,3oxathiolan-5-ones 8 results in clean extrusion of CO2 to give thiiranes,16,17 the closely related 1,3-dioxolan-4-ones 9 do not usually lose CO2 to give epoxides, but more commonly fragment by way of an α-lactone to give two carbonyl compounds and CO.18,2 When the oxazolidinediones 4 were subjected to FVP at temperatures in the range 700-750 ˚C a consistent pattern was observed.In each case the products were a mixture of benzaldehyde 13, the imines 12 and the nitriles 15 (not detected for 4c).The products together with their yields, as estimated from calibration of the NMR and GC data, are summarised in Table 1. a ca.5% 1-naphthylamine from hydrolysis of this also isolated.
We believe that these products are accounted for by the mechanism shown in Scheme 1, in which initial extrusion of CO 2 gives the α-lactones (aziridinones) 10.These rather elusive heterocycles were only obtained as isolable compounds in the 1960's,19 but the thermal decomposition of examples bearing bulky substituents was examined in a series of papers by Sheehan, 20-23 and found to give exactly the products corresponding to those obtained here.This is explained by a competition between loss of CO from 10 to give the imines 12 and rearrangement of 10 to give the isomeric iminooxiranes 11 which then fragment to give benzaldehyde 13 and the isonitriles 14 which under the conditions further rearrange to the more stable nitriles 15.It is also notable that direct evidence for the presence of 10a (ca.15% yield) among the products from 4a was obtained with the observation of a singlet at δ H 3.72 in the 1H NMR spectrum which compares with the value of 3.67 reported for 10c. 24GC-MS analysis showed that the products from 4a-c all contained minor components with the expected mass for α-lactams 10a-c and in the last case the fragmentation pattern was in reasonable agreement with that reported for 10c. 25 Of course these could also be the isomeric iminooxiranes but this seems unlikely since recent theoretical calculations have predicted the aziridinone isomer of the parent model system to be 26-31 kJ mol-1 more stable than the iminooxirane isomer. 26

Experimental Section
General Procedures.Melting points were determined using a Reichert hot-stage microscope and are uncorrected.Infra red spectra were recorded as nujol mulls on a Perkin Elmer 1420 instrument.NMR spectra were obtained for 1H at 300 MHz and for 13C at 75 MHz using a Varian Gemini 2000 instrument.All spectra were run on solutions in CD3COCD3 with internal Me4Si as reference.Chemical shifts are reported in ppm to high frequency of the reference and coupling constants J are in Hz.Mass spectra were obtained on an A. E. I./Kratos MS-50 spectrometer either using electron impact at 70 eV or chemical ionisation with isobutane as the ionising gas.GC-MS studies were carried out on a Hewlett-Packard 5890A gas chromatograph coupled to a Finnigan Incos mass spectrometer.

General procedure for preparation of 1,3-oxazolidine-2,4-diones
To a suspension of NaH (60% dispersion, 2 eq.) in dry THF (20 cm3) was added a solution of ethyl α-hydroxyphenylacetate 1 (1 eq.) in dry THF (3 cm3) at RT. Then a solution of the isocyanate (1 eq.) in dry THF (3 cm3) was added and the reaction mixture left for 18 h.The reaction was quenched with hydrochloric acid (1 M, 35 cm3) and the product extracted with ether (30 cm3).The ether layer was washed with hydrochloric acid (1 M, 2x35 cm3), dried and evaporated to give the product which was recrystallised as stated.

General Procedure for pyrolysis of 1,3-oxazolidine-2,4-diones
The sample was volatilised from a tube in a Büchi Kugelrohr oven through a 30x2.5 cm horizontal fused quartz tube.This was heated externally by a Carbolite Eurotherm tube furnace MTF-12/38A at a temperature of 650-750 ˚C, the temperature being monitored by a Pt / Pt-13%Rh thermocouple situated at the centre of the furnace.The products were collected in a Ushaped trap cooled in liquid nitrogen.The whole system was maintained at a pressure of 10-2 Torr by an Edwards Model E2M5 high capacity rotary oil pump, the pressure being measured by a Pirani gauge situated between the cold trap and the pump.Under these conditions the contact time in the hot zone was estimated to be ≈10 ms.