// lRepriatcd froo thc Jourad of tbc Aocrtc-' Chonicd Socicty, t?, {878 (1965).1 Nuclear MagneticResonance Spectroscopy. The ConfigurationalStability of Primary GrignardReagents. Structure and Medium Effects GeorgeM. Whitesidesand John D. Roberts IReprinted from the Journal of the American ChemicalSociety, 87,'1873 (196.j).I Copyright l9ti;i by the American Chemical Society and reprinted by permissionof the copyright owner NuclearMagnetic Resonance Spectroscopy. The ConfigurationalStability of Primary Gri-snard Reasents. Structureand Medium Effects' GeorgeM. Whitesidesand John D. Roberts Contribution lVo.3172 from the Gutes and Crellin Laboratories of Chemistry, Culifornia Instituteof Technology,Pasadena, CuliJ'orniu. ReceivedJanuarv 9, 1965 Qualitative and semiquontitative examination of the This observationsuggests that careful examination of lemperaturedependence of the RCH,:-Mg proton n.m.r. the spectrum oi this and related compounds in dif- spectra of several Grignard reagents indicates that the ferent solventsand at different concentrationsmight rate of inversiortat this center is relativel-v*insensitive to provide data pertinent to the mechanismof this in- the structurc of the group R. Secondar),Grignard re- version and to the nature o[ Grignard reagentsin ugentsinvert much more slowlv, if at all. The dependence solution. of the inversion rate of the primary orgonometallic Much of the modern work concernedwith the struc- compoundson solventcharacter and on added salts sug- ture of Grignard reagents has centered around at- gests that inversionproceeds br means of a mcchunism tempts to evaluate the importance of the so-called having kineric order greater than one. Schlenkequilibrium in describingthe Grignard reagent' In several well-known experiments, Dessy and co- workers examined the exchange reaction between Introduction labeledmagnesium bromide and diethyl-{and diphenyl- The precedingpaper2 presentedn.m.r. spectralevi- 2RMgX.- RIMB'MgX,=- R:Mg+ MgXz dencedemonstrating that 3.3-dimethylbutylmagnesium chlorides in diethyl ether solution undergoesrapid magnesium,sand concludedfrom theseexperiments that inversion of configuration at the CH:-Mg center. theequilibrium R 2RMgBr--- RrMg f MgBr'r HA' Ha H.r. i Ie, +M was not important in the Grignard reagentsstudied' \l-( In addition. conductometric measurementswere re' H H H. IH lvlgX ported to give identicals values for the dielectric con- stant of a I :l mixture of diethylmagnesiumand mag- (l) Supportcd in part by the Office of Naval Researchand the NationalScience Foundation. nesium bromide and of an equivalentconcentration ot' (2) G. M. Whitesides,M. Witanowski, and J. D. Roberts,.1. Am. "ethylmagnesium bromide."6 It was therefore con- Chem.Soc., 87, 2854(1965). (3) For convenience,the organometalliccompound formed by reac- (4) R. E. Dessy,G. S. Handler, J. H. Wotiz, and C. A' Hollings- tion of an alkyl halide with magnesium in an ethereal solvent rvill worth,J. Am. Chem.Soc.,79,3476 (1957). again bc calledan alkylmagncsiumhalidc. (5) R. E. Dessyand C. S. Handler,i6i(/.,80' 5824 (1958). 4878 Journul ol'rhe Anterican Chemical Socierv i 87:21 ,t November 5. 1965 (CH3)2CHCH.CH.MgClCH3CHzCH.CH.MgGI ((cn.).cxcH.cE.).Ms (CH!CH2CH.C!.).Mg J']|il'."4*'" ff"il.'-48 -51" 780 26" tl\ I IU\i\ / vl ilL /\ /tr M + '57" -73" 3lo 7go rrA,r'L J r't/\h Figurel. Spectraof the CH:-Mg protonsof 3-methylbutyl- Figure2. Spectraof the CH:-ilfg protonsoi bis(3-methylbutrlt- magnesiumchloride and rr-butylmagnesiumchloride in dierhy,l magnesiumand di-rr-trutytmagnesiurnin diethyl ether as a funcriorr etheras a functionol'temperature. of temperature. cluded that the Grignard reagentsstudied were best work on the structure of Grignerrd reagents in solutittn representedby the equilibrium and that no species must take into consideration the oossibilitv of its er- representedby the formula "RMgX" is presentin solu- istence. tion.7 Recently however, Stucky and Rundles and Ashby Results and Beckere have presented data suggesting that Organomagnesiumcompounds derived from halides Dessy'sconclusion may have been premature. Stucky similarin structureto 3,3-dimethylbutylchloride sh()w and Rundle demonstrated by the X-ray crystal struc- an analogoustemperature dependence in their spectra. ture determination of, phenylmagnesiumbromide di- Thus, the spectraof the CH:-Mg protons of 3-methy[- etheratethat the magnesium atom was tetrahedrally butylmagrtesiumchloride and n-butylmagnesiumchlo- coordinatedto one phenyl group, one bromide atom, ride are triplets at room temperature:at -50o. thc and two oxygen atoms; that is, that this Grignard spectra become more complicated (Figure l). Tire reagentwas in fact "RMgBr.2E,trO" in the solid degree of complexity is unfortunately sufficientlv state. great to discourage attempts to analyze the spectri.r Ashby and Becker were able to obtain a crystalline explicitly. The 3,3-dimethylbutylgroup provides i,r solid from a tetrahydrofuran solution of ethylmag- particularly simple system for analysis.because the nesiumchloride whose empirical formula corresponded four protons of the ethylenefragment are not coupled to EtMgzClr.THF. This fact, and their observation to the protons of the t-butyl group. In the 3-meth-"-l- that ethyI Grignard reagent was monomeric in tetra- butyl and rr-butyl derivativeshowever. the chemicll hydrofuran. led them to conclude that the most im- shift between the methyl protons and the adjacent portant speciesin solution was actually EtMgCl. methyleneprotons is of the same order of magnitude Both of these studies depended on compounds ex- as the coupling constant betweenthem, and the Lr- isting in the solid state, and in consequenceneither proton spectrumis consequentlycomplicated. r0 is necessariiypertinent to the structure of the Grignard Although little quantitativeinformation can be ob- reagent in solution. However, the X-ray study in tained from the spectrao[ theseGrignard reagents.or particular provides evidencethat "RMgX" may exist from the spectraof the correspondingdialkylmagnesiunr under suitable conditions, and suggeststhat further compound (Figure 2), qualitativecomparison with the 3,3-dimethylbutylmagnesiumcompounds makes clear (6) The contradictionwith a previous report is unexplained: R. E. Dessyand R. M. Jones,J. Org. Chem.,24, 1685(1959). two similarities in their temperature dependence. (7) R. E. Dessy,ibid.,25,2260 (1960). However, see R. E. Dessy, The first of theseis that the low-temperaturespectrr ot S. E. I. Green.and R. M. Salinger,TetrahedronLetters,2l,1369 (1964), the Grignard reagentsare very similar to the roonr- and D. O. Cowan,J. Hsu, and J. D. Roberts,J. Org. Chem.,29,3688 (1964),for evidencethat in fact the Schlenk equilibrium may be rapidly temperature spectra of the corresponding dialkyl- esublished. magnesium compounds. The second is that the (8) G. D. Stucky and R. E. Rundle, J. Am. Chem. Soc., E5, l@2 ( le63). (10) F. A. L. Anet, Can.J. Chem.,39,2262(1961); J. I. Musher and (9) E. C. Ashby and W. E. Becker,ibid.,E5, I l8 (1963). E. J. Corey, Tetahedron, lE,79l (1962). lI/hitesides, Roberts I Configurational Stabilitt' oJ' Primary' Grignard Reagents .1879 group near a center of Grignard reagent spectra do not seem to change at The protons of a methylene magnetically non- temperaturesbelow approxi.mately -70", and the molecuiar asymmetry may be n.m'r' spectra'I I diatkylmagnesiumspectra change little below *30o. equivalent and display AB-type that conformational Both of theseobservations are compatible with the RLcent investigations indicate major parl of the explanationpreviously proposed for the temperature preference is rlsponsible for the protons'r 1'1: dependenceof the spectrum of 3'3-dimethylbutyl magneticnonequivalence of the methylene which might be expected Grignardreagent based on the rate of inversion. More' A f,rimary-huu. Grignard reagent methylenep-rotons ouei. the seconclof . these observations would be dii- to magnetically nonequivalent rotational conforma- ficult to reconcilewith important changesin popula- would thus-be one in which one bond would be tions of rotational conformations with temperature. tion around the a,p-carbon-carbon other two. The I[ changesin the populations of the trans and gauche significantlylower in energythan the reagents,2-phenyl- conformations were important in determining the CffrfUg piotont of two Grignard 2-phenyl'3-methylbu- temperaturedependence of thesespectra, the broadening propylitognesium bromide and for evidenceof observeciin the central tine for di-rr-butylmagnesium iytmagnetiu.n chloride, were examined hydrogens compared with n-butylnlagnesiumchloride would be magnJtic nonequivalence. The a-methylene had an Az-type the consequenceof an increase in the energy dii- of ihe former in diethyl ether solution -80o (viscousbroadening pre- lerence between trans and gauche conformations of spectrumfrom *33 to temperature). The thesecompounds. Decreasingthe temperatureo[ the vLnted measurement below this had a spectrum char- Grignard reagentproduces a broadeningof the central methylene prorons of the latter spectrumat room line of its spectrum. Ii this changewere a reflectionof acteristicof the AB part of an ABX collapsedto an changesin confornter populations. lowering the tem- temperature:at +ll0o, the spectrum perature of the dialkylmagnesiumcompound should A:X type(Figures 3 and 4). of the temperature resr.rltin an analogoLrschange in its spectrum. In The most plausibleinterpretation of 2-phenyl'3-methyl- fact.little change in thc spectrumo[ the lattercompound dependence