摘要:

1676 J.C.S. Perkin I12-Halogeno-3-morpholinothietan 'I ,I -Dioxides. Kinetics of Base Cata-lysed cis-trans-lsomerization and Hydrogen-Deuterium ExchangeBy (Mrs) Silvia Bradamante, (Mrs) Paola Del Buttero, Dario Landini, and Stefan0 Maiorana,* lstitutodi Chimica lndustriale dell'llniversits di Milano, C.N.R. Centro di studio sulla sintesi e stereochimica dispeciali sistemi organici, Via Golgi 19, 201 33 Milano, ItalyThe kinetics of base catalysed H-D exchange a t position 2 and cis-trans-isomerization have beeen measuredin CD,CN-D,O for a series of 2-halogeno-3-morpholinothietan 1 ,I -dioxides (1 )-(6). The isomerization andexchange rates depend upon the nature of the halogen and are in the order I > Br > CI. The results are ration-alized in terms of electrostatic and/or steric effects.The values of the ratio k,,/k,, are ca. 1 for compounds(1 )-(3) and further support the known configurational instability of strained a-sulphonyl carbanions.IN a previous paper,l we reported the synthesis andstereochemistry of several cis- and tra:m-2-halogeno-3-morpholinothietan 1 ,l-dioxides. For the series of 4,4-dimethyl substituted derivatives (1)-(6) particularly,the cis-isomers are thermodynamically less stable thanthe tmizs-isomers as configurational isomerization easilyand irreversibly occurs in mild basic medium. t Duringthat work a qualitative dependence of the isomerizationwas also noted.The above observations prompted us to make quanti-No cis-isomer is present (by n.m.r. in trans- tative measures on base catalysed cis-trans-isomeriz-ation and H-D exchange in compounds (1)-(6) in order somers produced by base catalysed isomerization.1 P.Del Buttero and S. Maiorana, J.C.S. Perkin I , 1973, 2540. to evaluate which effects influence reaction rates1974 1677C'HsON XMe ,+----SO,Me( 1 ) X = C l( 2 ) X = B r( 3 ) X = Ic isMet r a n s( A ) x = c 1(5) X = B r(61 X = IRESULTSThe isomerizatioii and exchange kinetics were carriedout in [2H,]acetonitrile-D,0 solution (4 : 1 v/v) a t variouspH values using Na,B,O, or Na,B,O,-Pu'aOD as bufferagents at 40' (Table). In all cases the products weretmzs-2-deu terio-2-halogeno-4,4-dimethyl-3-morpholino-thietan 1, l-dioxides with an isotopic and isomeric purity ofat least 950/:, .f The deuteriation and isomerization rateswere followed simultaneously by careful integration of peaksclue respectively to the protons in position 2 and to theand those incorporating both the carbanionic centre andthe sulphonyl group in a cyclic four- or five-memberedring structure has already been clearly pointed 0 ~ t .2 - 4Moreover a sharp decrease in the barrier to inversionhas been shown for cyclopropyl carbanions substitutedby a phenylsulphonyl group.S At the moment it isdifficult to envisage a plausible explanation for thisbehaviour which does appear to be quite general. Theother kinetic results [see points (ii) and (iii)] can berationalized on the basis of steric and electronic factorsin the light of the particular stereochemistry of thethietan dioxide ring and taking into account of thehalogen atoms.The stereocheniistry of the isomers (1)-(6) haverecently been studied by lH n.m.r.ana1ysis.l Theresults, in accord with the crystal structures determinedby X-ray analysis of the cis-derivative (1) and of r-2-chloro-2,4,4-trimethyl-t-3-morpholinothietan 1, l-di-oxide7 as models, show that the thietan dioxide ring ispuckered and that in the probably preferred conform-ation the halogen is in a pseudoaxial (cis-series) or in aExchange and isoinerization rates of 2-halogeno-4,4-dimethyl-3-n1orpholinothietan 1 , l-dioxides ( 1)-( 6)( 0 . 2 5 ~ ) in CD,CN-D,O (4: 1 v/v) at 40 f 0.1"Compound p1-I: (f0-01) 1O3[Base]/nf e 105k&-1d 102Kis/l mol-l s-l 105k,,/s-1 102K,,/1 niol-1 s-l11.38 a 2.40 8.46 3.54 8.76 3.6512.95 88-6 310.0 3-50 330.0 3-7213-10 126.0 436-0 3.4611.38 a 2-40 21.6 9-02 21.8 9.0811-38 a 2.40 59.3 24.7 62.0 25.811-38 a 2-40 148-2 61.811-38 2-40 292-1 121-7(6) 11-38 a 2-40 383.6 159.8(1)( 2)(3)( 4)(5?a ~ b Apparent pH of buffer solutions of Na,B,O, and Na,B,O,-NaOD respectively.e Calculated irorn pH values. d The rateconstants are computer generated using the least squares method and arc the average of at least three runs.methyl groups in position 4 (see Experiiiiexital section).'l'he rates for both excliaiige and isomerization were firstorder in both base and sulplione (Table). Inspection ofthe Table also reveals that under our experimental con-ditions (i) in tlic cis series the key/kjg values arc ca. 1,(ii) isomerization and cleuteriation rates depend upon thenature of the halogen and decrease in the order I > Br >(11, and (iii) escliange is faster in the case of the tmvzs-isomers though the reaction rate (i.e.exchange withinversion) of the cis-tlerivati\-cs depends more on theiinturc of t h e halogcn.DISCUSSIOXThe first point that criierges from the results is thehigh configurational instability of these strained a-sulphonyl carbanions (Ke,/kis ca. 1). The differentoptical stability of the open chain a-sulphonyl carbanions7 See footnotc on p. 1676.The steric influence on thc rate of the exchange with inversioncan be related t o the steric acceleration affecting the Sh-1 nucleo-philic substitutions.& Also the hypothesis of thc intcrniediacyof a pyramidal carbanion with a very low barrier t o inversiondoes not disprovc thc above considerations.An analogouseffect is reported 9 t o contribute to some degree in deterniiningthe H-D exchange ratc in the halogenoforms (CDT, 3 CDBr, >(*,DCI J.2 L. A. Paquette, J. P. I~ree~nan, and M. J. Wyvratt, J. Anier.Chcirr. Soc., 1971, 93, 3216 and reference therein.pseudoequatorial (trans-series) disposition. Moreoverin the former series stronger steric interactions betweenthe ring substituents must be expected, since thechlorine atom is eclipsed by one of the oxygen atoms ofthe sulphonyl group and is in a l,%pseudoaxial relation-ship with one of the inethyl groups in position 4.Thissteric hindrance is the driving force that through theformation of the carbanion, its inversion, and theconsequent relief of strain, promotes exchange withisomerizatioii in the &series.$ These criteria, in linewith the experimental results, are expected to have thegreatest effect in the case of the iodo-derivative.As for electrostatic effects, repulsion on the anionic,incoming base should reach a minimum in the case of3 E. J. Corey, 11. Konig. and T. H. Lowry, TctrahedvonLctters, 1962, 515.4 D. J. Cram and T. A. Whitney, J . Anzrr. Cltein. Soc., 1967,89, 4651.6 A. Ratajczak, F. A. L. Anct, and D. J. Cram, J . Ainer.Cliem. Sac., 1967, 89. 2072.8 G. I). Andreetti, G. Bocelli, and I?. Sgarabotto, Gazsetta,1974, in the press.7 G.D. Anclreetti, L. Cavalca, and P. Sgarabotto, Gazzetta,1971, 101, 440.8 E. S. Gould, ' Mechanism and Structure in Organic Chem-istry,' Holt, Rinehart, and Winston, London, 1969, ch. 8, p. 274.a J. Him, N. W. Rurske, M. Hine, and P. B. Langford, J .Awzer. Chem. SOC., 1956, 70, 14061678 J.C.S. Perkin I1iodine, which is the least electronegative and the mostpolarizable atom of the halogens. This effect is inaccord with the observed order of reactivity (I > Br >CI) in the trans- (exchange) and in the cis-series (exchangewith inversion) .t The less pronounced differences inreactivity observed in the trans-iodo-, -bromo-, and-chloro-derivatives (6), (5), and (4) (2.6 : 2 : l), withrespect to those of the cis-isomers (3), (2), and (1)(7 : 2.5 : 1) are in line with the above considerations. Infact, as shown before, only electrostatic factors controlthe exchange rates in the former case, whereas bothelectrostatic and steric effects operate in the latter.The greater H-D exchange rate of the trans-isomers withPx cis transFIGURErespect to the cis, cannot be accounted for by sterichindrance towards the incoming base since a scale ofreactivity opposite to that found would be expected.In fact, 2-H is less sterically hindered in the cis-series.A plausible explanation can be envisaged in the par-ticular position of the exchanging proton with respect tothe OSO angle.In fact it is known that H-D exchangeof a proton cc to a sulphonyl or sulphinyl group dependsmarkedly on its orientation with the groups.12 In ourcases, as pointed out previously, the 1H n.m.r.data, theX-ray analysis, and the molecular models show that inthe most probable ground state conformation, 2-H liesinside the OSO angle in the cis-series and outside in thetrans l y 6 s 7 (Figure). We presume that in the transitiont The same reactivity scale has been found for H-D exchangein the case of the a-bromo- and chloro-acetone.10 Moreover,the different polarizabilities of halogen atoms would affect thecarbanion stabilities in such a way that the same order of re-activity would be expected. The same situation would be metif the destabilization factor (+ R effect) on carbanions is opera-tive.lIAAstate, whatever it is, the two hydrogens should have adifferent orientation with respect t o the OSO angle, thusaccounting for the differences in the H-D exchangerates.AEXPERIMENTALThe 1H n.m.r.spectra were taken with a Varian A 60-4spectrometer with tetramethylsilane as internal standard.pH Measurements were performed on an Amel model 332potentiometer .Products.-The preparation and the physical propertiesof compounts (1)-(6) have been reported e1sewhere.lHowever the m.p.s of compounds (1) and (4) reportedtherein should be inverted and are 157 and 132" respectively.Reagents and Solvents.-Commercial [ZH.Jacetonitrile wasused without further purification. A 0 . 0 1 ~ solution ofAnalaR grade sodium tetraborate (10 ml) in D,O wasdiluted to the mark with [2H,]acetonitrile in a volumetricflask (50 ml) in a constant temperature bath (40 f 0.1').This solution showed a constant apparent pH of 11-38 &0.1 after four days.Solutions of higher pH were obtainedby adding the appropriate amount of O-lN-NaOD solutionin D,O to the buffer solution at pH 11-38.Kinetics.-Substrates (1)-(6) (0.25 minol) were dissolvedin the buffer solutions (lml) in an n.m.r. tube a t constanttemperature (40 f 0.1') and the tube was placed in then.m.r. probe thermostatted at 40 & 0.1". H-D Exchangewas followed by integration of the doublets centred a t6 4-63, 4.56, and 4.35 and 4.72, 4.69, and 4.53 [CHCl of(1)-(3) and (4)-(6) respectively]. The isomerization ratewas simultaneously measured through integration of the4,kdimethyl group signals. Pseudo-first-order rate con-stants were calculated on a UNIVAC 1106 computer usingthe least squares method. Average deviations fromaverage values of K from at least triplicate runs wereca. & 6%.We thank Professors F. Montaiiari and L. A. Paquettefor discussions and CNR, Roma, for financial support.[4/846 Received, 26th April, 19741lo R. P. Bell and 0. M. Lidwell, Proc. Roy. Soc., 1940, A, 176, 88.l1 K. J. Klabunde and D. J. Burton, J . Amer. Chem. SOC.,1972, 94, 5986.la R. R. Fraser, F. J. Schuber. and Y. Y . Wigfield. J . Amer.Chem. Soc., 1972, 94, 8796 and references therein; R. R. Fraserand F. J. Schuber, Chem. Comm., 1969,1474

ISSN:1472-779X    

DOI:10.1039/P29740001676

出版商:RSC    

年代:1974

数据来源: RSC