摘要:
1975Stereospecific Syntheses of (2)- and (€)-4-Brornomethylene-5,5-Di-methyl-3- Phenyloxazol id in-2-oneBy Christopher C. Browne and Natim Punja,' ICI Plant Protection Division, Jealott's Hill, Berkshire RG12 6EY3-Bromo-1 ,I -dimethylprop-2-ynyl carbanilate undergoes base-catalysed cyclisation to give (Z)-4-bromo-rnethylene-5.5-dimethyl-3-phenyloxazolidin-2-one. Bromination of 5.5-dimethyl-4-rnethylene-3-phenyloxazoli-din-2-one, followed by dehydrobromination, gives the €-isomer. The stereoisomers have been characterised byn.m.r. spectroscopy. The stereospecificity of each reaction is rationalised in mechanistic terms.THE base-catalysed cyclisation of prop-2-ynyl carb-anilates to 4-methyleneoxazolidi-2-ones is well estab-li~hed.l-~ We now report stereospecific syntheses of(2)- and (E)-4-bromomethylene-5,5-dimethyl-3-phenyl-oxazolidin-2-one.Halogenoacetylenes normally react with secondaryamine nucleophiles at the terminal acetylenic carbonatom bearing the halogen atom.For instance, 1-bromo-2-phenylacetylene reacts with diethylamine togive l,l-bisdiethylamin0-2-phenylethylene.~ Similarlyalk-l-ynamines have been prepared from l-chloro-acetylenes and secondary amines.7 Thus, intramolecularcyclisation of 3-bromo-1 , l-dimethylprop-2-ynyl carb-anilate (I) might be expected to give the oxazin-2-one(11). However, this would be unlikely on stereo-chemical grounds in view of the linearity of the acetylenefunction. The reaction of compound (I) (or alternativelyof 4-bromo-2-methylbut-3-yn-2-ol with phenyl iso-cyanate) in the presence of a catalytic amount ofsodium methoxide, in fact, gives a crystalline productshowing vao 1770 cm-l, indicating the oxazolidin-2-onestructure (111) rather than the oxazin-2-one structure(11) which would be expected to show vco ca.1690cmll.QJo Hydrogenolysis of the product over Adamscatalyst gave the 4-methylene derivative (IV), identicalwith a sample prepared by an alternative method.2Bromination of compound (IV), followed by dehydro-bromination with triethylamine, gave the stereoisomericbromo-derivative (V) which was a crystalline solid,lower melting than (111), showing vao 1775 cm-l.Each stereoisomer gave an n.m.r. signal for =CHBr at7 4.9.The geometry of the C=C bond in the stereoisomers(111) and (V) was assigned by n.m.r.spectra. Irradiationat the frequencies corresponding to the 2- and 6-protonsof the phenyl group and to the methyl protons of (111)and (V) caused appropriate nuclear Overhauser enhance-ments of the =CHBr signal. In the case of (111), noenhancement was observed on irradiation at the phenyl2- and 6-proton frequency, whereas (V) showed anenhancement of 26% under the same conditions.However, irradiation a t the methyl frequency of (111)gave an enhancement of 42% as compared with onlyM. D. Cameron, U.S.P. 2,844,960/1968.N. Schachat and J. J Bagnell, jun., J. Org. Chern., 1963, $38,P. J. Stoffel and A. J. Speziale J Ovg. Chem., 1963,28, 2814.N. R. Easton, D. R. Cassaday, and R. D. Dillaxd, J. Org.R. Sisido, J .Hukuoka, M. Toda, and H. Nozaki, J. Org.991.Chem., 1962, 2'7, 2927.Ckcrn., 1962, 27, 2663.5% for (V). These results agree with the assignedstereochemistry.f H-XII0(I1$HII0II0 LIBr JH21-HBfLII0II0Addition of tris-( 1,1,1,2,2,3,3-heptafuor0-7,7-di[~H&me thyloctane-4,6-dionato) europium [ Eu (f od)J resultedin the shifts listed in Table 1. The results suggest thatthe position of association in (111) and (V) is the sameand similar to that in (IV) (in which the smaller shiftsare probably due to reduced steric hindrance). Thus itcan be inferred that the site of association is close to thecarbonyl group and that the exocyclic methylene protonin (111) is closer to the gem-dimethyl group than thephenyl group, whereas in (V) the reverse is true.The formation of the Z-isomer (111) may be rationaI-ised in terms of deprotonation of the carbanilate nitrogenatom by sodium methoxide, followed by addition of thea V.Wolf and W. Block, Annalen, 1960, 687, 119.H. G. Viehe and M. Reinstein, Angew. Chem. Internat. Edn.,* F. Straus, L. Kollek, and W. Hyn, Ber., 1930, 68, 1868.9 A. Hassner, P. R. Hoblitt, C. Heathcock, J . E. Kropp, andlo J . P. Liand J. H. Bell, J. Org. Chem., 1970, 3!j, 4100.1964, 3, 606.M. Lorber, J . Amer. Chem. SOC., 1970, 92, 13261526 J.C.S. Perkin Initrogen nucleophile to the internal acetylenic carbonatom with concomitant abstraction of a proton fromthe medium. The E-isomer may be formed as a resultof P-elimination of hydrogen bromide from the con-former which leads to the least hindered and thermo-dynamically more favoured isomer.TABLE 1Lanthanide-induced shifts * for compounds (111)-(V)Phenyl2-Compd. and 6-H CMe, =CH6.76 8.2 8.24.9 7.86 7.86 and 7.36.8 8.2 7.16* Values in p.p.m.obtained by extrapolating the tangent tothe chemical shift YS. Eu(fod), molar ratio curve a t zero[Eu(fod),] to a 1 : 1 molar ratio.TABLE 2(2) -5,5-Dialkyl-3-aryl-4-halogenomethyleneoxazolidin-2-ones(111)(IV)(V)R1 R2Me MeMe MeMe E tMe EtMe EtMe E tMe But0R3 XPh Brm-ClC6H4 BrPh Br%-C1C&4 BrPh c13,4-C1 C H C1 P Y BrPh c1Ph BrPh ITABLE 3Yield88808676698680787270(%)M.p.16616813414313814286188168179( "C)(E) -5,5-Dialkyl-4-bromomethylene-3-phenyloxazolidin-2-ones,Brii0('1111)Yield M.p.R' R2 (%I ( "C)Me Me 74 121Me E t 70 72CCHJ, 68 124The foregoing stereospecific reactions are quite general,and have been used to obtain several (2)- or (E)-5,5-dialkyl-4-bromomet hylene-3-phenyloxazolidin-2-ones(see Tables 2 and 3).Furthermore, (2)-5,5-dialkyl-3-aryl-4-halogenome t hyleneoxazolidin-2-ones have beenprepared from 3-chloro-, 3-bromo-, and 3-iodo-l,1-dialkylprop-2-yn-1-01s and aryl isocyanates (see Table 2).This is apparently the first reported example of a base-catalysed cyclisation involving addition of a nitrogennucleophile to a halogenoacetylene at the carbon atomto the halogen atom.EXPERIMENTALUnless otherwise stated, cyclohexane was used as solventand sodium methoxide as catalyst.1.r. spectra were deter-mined for Nujol mulls with a Perkin-Elmer Infracordspectrometer, and n.m.r. spectra for solutions in carbontetrachloride with tetramethylsilane as internal standard,with a JEOL MHLOO spectrometer. M.p.s were determinedwith a Kofler hot-stage apparatus. The following prepar-ations of compounds (111) and (V) illustrate the generalmethods used. Details of the products listed in Tables 2and 3 are available as Supplementary Publication No. SUP21392 ( 5 pp.).?(2) -4-Brornornethylene-5,5-dimethyl- 3-phenyloxazolidin- 2-one (111) .-(a) To 3-bromo-l,l-dimethylprop-2-yny1 carb-anilate (14.0 g, 0.05 mol) in cyclohexane (75 ml) was addedsodium methoxide (0.03 g).The mixture was stirred at45-55 "C for 1 h and then allowed to cool to room tem-perature. The precipitate was filtered off and recrystallisedfrom ethanol to give a product (12.3 g, 88%) identical (m.p.,mixed m.p., and i.r. and n.m.r. spectra) with that obtainedby method ( b ) .(16.3 g, 0.1 mol)in cyclohexane (125 ml) was added sodium methoxide(0.05 g). Phenyl isocyanate (12.0 g, 0.1 mol) was thenadded dropwise with stirring at such a rate as to maintainthe reaction temperature at 45-55 "C. The mixture wasallowed to cool to room temperature and stirred for 1 h.The precipitate was filtered off and recrystallised fromethanol to yield prisms (21.0 g , 75%), m.p. 155O (Found:C, 50.9; H, 4.3; Br, 28.1 : N, 5.0.C,,HI2BrNO, requiresC, 61.05; H, 4.3; Br, 28.3; N, 4.95%); v,, 3080, 1770,1 650, and 1 590 cm-l; T 2.64 (5 H, s), 4.94 (1 H, s), and8.42 (6 H, s). The product (1.4 g, 0.05 mol) in methanol(100 ml) with Adams platinum catalyst (0.05 g ) absorbed105.8 ml of hydrogen at 20 "C and 758 mmHg in 45 min togive, after filtration and evaporation, a solid (0.8 g) identical(i.r. spectrum, m.p., and mixed m.p.) with authentic 5 3 -dimethyl-4-methylene-3-phenyloxazolidin-2-one.(E)-4-BromomethyZene-5,5-dimethyl-3-~henyloxazolidin-2-one (V) .-To a solution of 5,5-dimethyl-4-methylene-3-phenyloxazolidin-2-one (18.9 g , 0.1 mol) in carbon tetra-chloride (200 ml) was added a solution of bromine (16.0 g,0.1 mol) in carbon tetrachloride (50 ml) dropwise withstirring during 1.25 h at 0-10 "C.The solution was thenstirred for a further 2 h at room temperature. Triethyl-amine (25.0 g ) was then added during 10 min and stirringwas continued for another 2 h at 25-35 "C. The precipi-tated triethylammonium bromide was filtered off and thefiltrate evaporated in uucuo. Recrystallisation of theresidue from aqueous ethanol yielded pEutes (21.70 g,74%), m.p. 121O (Found: C, 51.1; H, 4.35; Br, 28.5; N,5.0%); v,, 3 080, 1 755, 1 660, and 1 598 cm-l; T 2.60( 5 H, m), 4.88 (1 H, s), and 8.20 (6 H, s).The product (1.4 g, 0.05 mol) in methanol (100 ml) withAdams platinum catalyst (0.05 g) absorbed 107.2 ml ofhydrogen a t 20 "C and 758 mmHg in 45 min to give, afterfiltration and evaporation, a solid (0.7 g) identical (i.r.t For details of Supplementary Publications, see Notice toAuthors No.7 in J.C.S. Pevkin I, 1974, Index issue.(b) To 4-bromo-2-methylbut-3-yn-2-01975 1527spectrum, m.p., and mixed m.p.) with authentic 5,5-di-methyl-4-methylene-3-phenyloxazolidin-2-one.23-Bromo- 1 , 1-dimethylprop-2-ynyl Carbanilate (I) .-TO4-bromo-2-methylbut-3-yn-2-01 (16.3 g, 0.1 mol) in cyclo-hexane (125 ml) was added phenyl isocyanate (12.0 g,0.1 mol) followed by 3 drops of triethylamine, and themixture was left a t room temperature for 6 h. Evapor-ation under reduced pressure and recrystallisation of theresidue from light petroleum (b.p. 60-80°) gave a crystal-line solid (26.5 g, 94%), m.p. 95" (Found: C, 51.1; H, 4.4;Br, 28.05; N, 4.4. C,,HI2BrNO, requires C, 51.05; H,4.3; Br, 28.3; N, 4.95%); vmH.3 370, 1730, 1620, and1 540 cm-l.Nuclear Overhauser Effect Measurements.-A solution ofthe compound (5 x 10-4 mol) in carbon disulphide (0.5 ml)containing 2% v/v dimethylformamide and 1 % tetra-methylsilane was degassed by freezing in liquid nitrogen,evacuating the tube to 0.1 mmHg, isolating the tube fromthe vacuum pump, and allowing the sample to thaw toroom temperature. This cycle was repeated four times andthe sample finally sealed under vacuum. The dimethyl-formamide served to aid dissolution of the compound andto act as measure of the suitability of the solution forn.0.e. measurements by comparison of the enhancementobtained for the formyl proton signal in each sample whenthe low field methyl signal was irradiated. In all casesthe enhancement was taken as the percentage increase ofthe average of seven integral traces obtained with irradi-ation at 7 10. For both compounds (111) and (V) theintegral of the =CHBr signal was measured while irradiatingfirst a t z 10, then at the CMe, singlet frequency, and finallya t the frequency corresponding to the centre of the doubledoublet assigned to the phenyl 2- and 6-protons. Theenhancement found for the formyl proton of dimethyl-formamide in the solutions of (111) and (V) was 25% in eachcase.Use of the Paramagnetic Shift Reagents.-To a solution ofthe compound (5 x lod4 mol) in carbon tetrachloride(0.5 ml), weighed amounts of Eu(fod), were added, andafter each addition the n.m.r. spectrum was recorded. Tensuch additions were made up to 1 : 1 molar ratio of shiftreagent to compound. Chemical shifts were plottedagainst the molar ratio of shift reagent to compound. Foreach curve the tangent at zero concentration of shiftreagent was extrapolated to a 1 : 1 molar ratio to give aninduced shift value.We thank Messrs. M. R. Kipps and D. G. Greatbanks for[4/1812 Received, 2nd September, 19741determination of n.m.r. spectra
ISSN:1472-7781
DOI:10.1039/P19750001525
出版商:RSC
年代:1975
数据来源: RSC