(1980).1 [Reprinted {'romthe.lor.rnral ol the American Chemical Societ,-v,102, 2;]1 Copyright ,citOSOby the American Chemical Societvand reprint,edbv permissionof'the copyright owner

Mechanismof Formationof GrignardReagents. Kineticsof. Reaction of SubstitutedAryl with Magnesiumand with Tri-n-butyltinHydride in EtherealSolventsl

Harold R. Rogers,2Randall J. Rogers,H. Lee Mitchell,'land GeorgeM. Whitesides* C6ntributionfronr theDepartnent oJ'Chemi.strt', Massachusetls Inslilute of Technologl', Cuntbridge,Mo.ssathu.tett.\ 01139. ReceiredSeptenther ll, 1978

Abstract:llarlntctt constantsfor rcuctionof'substiturcd arllbronridcs with nragncsiumin scvcrillstllvcntslirlltlrl:dicthylcthcr (p:l.l):di-n-butylcthcr(r,,=1.9):-l:lr:r'di-rr-butllethcr crclohcranc(p:1.0):tctrahvdrol'uran(p-0):J:lv:vtctrahl'- - drolunrn hcxanrcrirvlphosphonrnride(/r r 0):dicthrlcthcr contuining0.lJ N{ clclopcntl'lnrrtgnesiunl bronlidc (ir 0) In thc pollr sglvcnts.rcactlgn uppcars ttt bc nrasstrrrnsport lirnitcd. The rrrtcol'rcrtction ol'lrrll iodidcswith ntagncsiunlin dicthrl - cthcr is probablyalso masstnrnsport lintitcd (p : 0). Thc ratc of'rcactionol'chlorobcnzcnc with rnagncsium(pr 1.0) is ca. l0a slowlcrthan that ol'bronrobenzencin dicthll cthcr. and is not nrasstransport lrmitcd. The rcactittnol'rtrvl bronlidcswith tri-rr-buty'ltinhldride (AlBN. hr,)has p = l.-1.Analysis olthcsc valucsof p narrowsthc choiccf or the ratc-dcterminingstcp in the rcactionol'bromobcnzenc with magncsiunrin dicthy'lcthcr to onc of threc limiting possibilitics:clcctron Lransfer from thc nrctaltp thc a11,lbrontidc (3). ury'lradical tirrnrationb),bronrinc abstraction from thc aryl brornidcby thc mctal (6). or. lcssprobabll. inscrtionolu nugncsiunratonr into thc carbon bronrincbond (7).

Introduction with magnesiumwith lossof stercochemistryin all but a feu' cascs.I I lr Aliphaticradicals are effectively planar; unstabil- This papcr summarizesthe resultsof'a studl'of the influcnce izedvinylic radicals are bcnt but invertwith rateconstants of of substituentsand solventon the relativerates ol'reaction of ca. | 010.- | s1room temperaturc.l6 Loss of stereochemistry aryl halidcswith magnesiunrand with tri-n-butyltin hydride. of vinylicradicals might thus be expected to competeeven with Thesc studicsdifferentiate between solvents in which reactions thevcry fast reaction of freeradicals with (at) a with nragnesiumare masstransport limitcd and thosein which surfaceinferred from studiesof the kineticsand productsof reactionis slowerthan masstransport, but do not distinguish reactionof alkylhalides with magnesium.a'5'14'17'ltt bctwcenthe two most plausiblelimiting mechanismsfor the initial rcactionof organic halideswith magnesium:electron Results transfer (eq l) and halogenatom (or halide ) abstraction Hammett p ttaluesare similar reactionof aryl halides (cq 2) (in theseequations, Mg. representsa surfacemagnesium for with magnesiumand tri-n-butyltinhydride in diethylether atclm).a's solutions,but differ in THF solutions.Relative rates of re- - RX + Mg,- [RX-.] * Mg,*' R' + X- * Mg.*' (l) actionwere determined using competitive kinetics techniques.a Theserates were not sensitive to smallvariations in mostex- RX + Mg' - R' + X-Mg'*' (2) perimentalparameters (cf. ExperimentalSection). We did not Analogousstudies involving alkyl halidesare detailedin varythe stirring rate over a widerange, and we caution that accompanyingpapers.a'5 Aromatic bromidesare reduced theexperimental rate ratios are expected to showsome sensi- clectrochemicallyat approximatcly the same potential as alkyl tivity to this parameterwhen the componentrates are in- bromides,6but sp2carbon- bonds are strongerthan fluencedto differentextents by masstransport:a competitive sprcarbon-bromine bonds, and a hypotheticalaryl rate measurementsinvolving rates close to transportlimited radicalanion might be longerlived than an alkyl bromide must be interpretedwith care.Figure I givesrepresentative radicalanion.6 | I Further,stereochemical evidence suggests experimentaldata for reactionsof pairsof aryl bromideswith that reactionsof vinylic(and, by analogy,aromatic) bromides magnesium;Figure 2 showssimilar data for reductionsof aryl with magnesiumdiffer from analogous rcactions of aliphatic bromidesby tri-n-butyltinhydride (ftv, AIBN). bromides:the reaction of scvcralstereoisomeric vinylic halides The rates summarizedin Table I were correlatedwith with magnesiumproceeds with significantretention of ste- substituenteffects using Hammett o parameters(rather than, 2s) rcochemistry,l2while aliphatic organic halides appear to react say,half-wave reduction potentialsle becauseHammett 232 Journal oJ'the American Chentit'al Societl, I t02.t f Januort, 2, tgB0 'l'able l. Rclativc (AH/Arr) Rrlcs for Rcacrionsol'A11l Halidcs (RC6HaX) u,ithl\lagnesiunrand with Tri-rr-butt'ltinHvdridc,,

solv' I r r' R=X cl Br Br Br Br Br TF|F:Ilr [:t'(i: Br r "S'!+tBr Br OR" Br .l-OCt-| r 05l 0.69 0.78 0.66 0.76 0.n2 0.t{4 0.91 0.62 0.16 -0.27 -|.u4 'l-('ll r 0.69 0.-54 0.,54 0.-59 0.69 0.rJ6 092 092 0.u7 0.6-s 0.71 -0 17 - 1.84 _t-cH r 0.11 0.64 0.53 0.69 0.73 0.82 0.tt6 092 0 ltg 0.89 -0.07 - 1.8.5 HI I I rl I I I I I 0.00 -r.81 ;l-F 1.9 3.0 1.6 0.97 l.l 0.ti9 0.9t3 t.2 fr 1.4 0.06 l-oc'H r 2.0 l.rJ 1.6 0.92 ) l.l 0.r2 -t.16 'l-Cl 2.9,t 6.2 4.1 2.1 l.l 1.0 0.99 2.2 L. -) 0.2,1 -r.61 .1-Br (0.95),/ '' L-J 2.1 !.J 0.2-l l-F l1 -s.I 2.1 r.0 t.-) 4.5 -s.9 014 l-cl a1 t.J 2.3 0.93 1.0 4.2 0.37 - 1.53 3-Br ( t.3)/ 1.2" 4.1 -s.8 0.39 -l-CFr 4.u ^'l tt.u 2.5 096 0.82 0.99 I.l a.L +.' 0.42 - 1.59 4-CFr 1.2 3 7 0.83 r.0 -s.5 5.-s 0.-5 -s - l.-52 All rcactionswcrc ^ " carricdout usingstandard conditions dcscribed in thc Experimentalsedion. Ratcsin differentsolvents cannot bc comparcd. Rcproducibility of r{tiosof ratesin individualcompctition experimcnts was + 109o.THP istetrahydropyran; RMgBr EtlO isa 0.8 M solurion ol cyclopcntylmagncsiunrbronridcindicthylethcr;C6HDltuto.t:3.v:vtHMpA-THF, l:3.v:v. ncacrionsofArBrand Arl withMgwerc carricd oC: 'C. , .'Rates out at 0 reactionsofArCl with Mg wcrccarried out at 2l J. E. I-cfflcrand E.Crunwald, andEquilibria ofOiganic '.wil"). '.Half-wa.,,c Yorl. Iq6l. p 173. reduclionpotenriats vs. Ag/AgBr in ov r.rr d Stuiirricotty ro. ttr" pr.i"n"" ol|:j.tl9i\ lwo ldcnllcul f "w crrbon hrrlogcnbond\ by dividingthc observcdrate conslant by 2.0-. Not corrccledstatisticaily. "oiJ.aSce thc text for discus-

o- c)

(J - 0.5 orl ;

o- O F\ !2 ot o ''o -tosrcrz/c?, -fy Figurc2. picalduta for thc rcduction of substitutcd aryl bronridcs br trr-l-butl'ltinhvdridc in cthcr.Substitucnts for thc curves A c lirlltr* A1= 2-Clll,A: = nt,p-H.By= m,p-H,B: = 2r-CiH3. Ct = ,t-Br.untl 1'. = p_Cl.

cyclohcxane(3:l ). and diethylether containing 0.8 M cyclo- pcntylmagnesiumbromide. plots ).o o.5 t.o Hammett in tetrahydrofuran. tctra hy'dropyra n, and tetrahydrofuran - hexamethyl phospho- -tos tc:rtc\) -ry ramidc (3:l ) appcarto be slightlycurved. This slightcurvarurc liigure pical l. dutirf or thc rcactionsol' nragncsiunr with substitutcd notwithstanding,the r.atesin polar solvcntsare clearlymuch rrrrI brorliclcsin dicthl-le thcr. The substituentslbr thc curvcsA F-ftrllow: lcsssensitive to substituentsthan are ratesin diethylether and ,\r = /1,/)-ll,A2 =p-Cl, B1= p-( ll.r,B: = m,p-H.(-1=p-CF1, C: = = = = lcss polar solvents.Thus, the reactionsof aryl halideswith 7r-Cl.D1 p-('.1,1)3 p-Cllr, Er p-C[:r.and [:2= 7r-Cllr. Iri-n-butyltin hydrideand magnesiumrespond differently to solvcnteffects. The former givc a singlevalue of p. independent /) values are available for a number of other reactions. espe- ol'changesin solvent:the latter givevalues of p which depcnd cially hcterogeneous ones. Thc rates of reaction of aryl bro- stronglyon solvent. rnidcswith tri-//-butyltinhydridc havc indistinguishablep's The rate oJ-reaction rf ar1'l bromides is ma.gstransport in diethylcther and tetrahydrofuran(Figure 3. Table II). lt limited in THF and more polar.solt:ents,but not in dietht'l is not clcar whether this relativelylarge magnitude of p should ether and lesspolar solrents.The relativeratcs of reactionol' bc ascribcdto chargeseparation in the transitionstate or 10 bromobenzeneand cyclopentylbromide with magnesiunrin diffcrcncesin homolyticcarbon brominebond energics.16 :x diethyl etherdiifer only by a small factor: k1.or1,o,fkc-( slqrrr [;or comparison,abstraction of iodine atoms from substituted : 0.48.4The rate of reactionof cyclopentylbromide is merss iodobenzenes phcnyl by radicall')-a reactionin which sub- transportlimited in all solventslisted in Table 1.5We havc stituent el'l'ectshave been suggested2T to originatealmost en- cstablishcdthat thc smallvalue of p characterizingreactions tircly in p : bondenergies-has 0.57. of'aryl bromideswith magnesiumin polar solventsreflccls a plots Hammctt for the reactionsof aryl bromides with transport-limitedreaction using a procedureanalogous to that nrilgncsiumin several solventsarc givcn in Figure4; valucsof applied to neopcntylbromide.i Relativerates of reactionof ure listed /) in Table I I. Straightlines with similarscatter were cvclopentylbromide and bromobenzenewere measuredin two obscrvcdin diethyl ether,di-n-butyl ether. di-n-butyl crher- seriesof solutionsof increasingpolarity (Figure 5).30High ^11 Whitesides et al. f Reaction of Substituted Aryl Bromides with Magnesiunt LJS

TableII. Hammcttp Valuesfor Rcactionsof Aryl Halideswith log (kr/kr) Magncsiumand with Tri-n-butyltin Hydride and p Valuesfor O-F fjm-Br ModelReactions Involving Cleavage of Bondsto, or Electron P-cFs Transferwith. an Arvl Moietv m-CF' reaction solvent o.5 ArCl * Mg Et20 2.0+ 0.2 ArBr * Mg 3 Bu2O- I C6H 12 2.0+ 0.3 Bu20 1.9+ 0.3 Et20 l.t +0.2 THP <0.6-0.00 THF <0.5-0.00 m-OCH. 3THF I HMPA <0.40.0a f EtzO,RMgBr 0.1+ 0.2 q (0.8M) tr-cHg m,p-H Arl * Mg EtuO 0.2+ 0.2 p-OCH3O ArBr * Bu3SnH Et20 1.4+ 0.2 THF 1.3+ 0.2 P-cHs Arl * Ph. CCI+ 0.5'72e Arl * p-NO2Ph. ccl4 0.1-0.027 Arl * 2e- Hzo,2lDMF22 0.3,2r0.3522.2r ArBr * 2e- DMF 0.5122.b -o.5 ArCl * 2e- DMF 0.8122,b ArR * c- H:O 4.7, -OlCArR * c- HrO 0.14, m-CF ArzHg+ rorHg benzcne - I .0ll m-F ArD * H:O (Ptcatalyst) H:O 0.0rs ArH * KNH: NHr [-6]/ ArlFlg* HgX2 dioxanc - 5.9'' o.5 ArR * SO.r-. H'O -:.+1,ll r' " NonlincarHanrmett plots;scc Figurc 4 and thc text. Thcsc"p" valucsurc the slopesol plotsof on vs. C1,' I'rontpolarographic rc- ductionat a droppingmercury clectrodc. ' \4. Anbar. Atlr. Phv.s.Org. ('hem.,7, ll5 (1969);R = Br. I {'allof'f the corrclation lincs.'/ An O m-OCH. approxinratevaluc obtainedby' plotting partirrl ratc f'actorsfrorn A. I. Shatenstcin. ibid., l, 1,55( l96l), vs.op. Thc plot showsconsidcrablc scattcr." R. E. Dessyand Y. K. Lcc, J. Am. Chem.^9r-rt'., 82,689 D'P-H 11960)./ P. Ncta. V. Madhavcn,H. /.emcl.andR. W. Fessendcn. ihid.,99.r63 il977). P-ocH3o P-cHs

dielectric constants were obtained in one series of experiments (the upper plateauof Figure 5) using mixturesof THF and H M PA. Dielectricconstants of mixed solventswere estimated on thc assumptionthat contributionsfrom thc two components were additive. In a secondseries of experiments(the lower I,'igure3. [{lrnrrnettplots lbr rcuctionsol'substitutcd brtlnrtlbcnzcncs with (AIBN./rrr): ,\:Tlll'. plateauof Figure 5), ethercontaining high concentrationsof tri-r-butlltrnhldridc undcr l-rec-radicalconditions 1r':. 1.3:U: t--tro. p - 1.1. cyclopentylmagnesiumbromide was usedto obtain high di- clcctric constants.Dielectric constants for thesesolutions were assumcdto be the same as thosefor corrcspondingconccn- trationsoi cthylmagncsiumbromidc in dicthylcthcr.rl variousconccntrations of cyclopenty'lmagnesiumbromide. The Figure 5 effectivelyrelated the rate of reactionof bromo- valueof p in dicthylcthcr containing 0.8 M cyclopentylmag- bcnzencto the rate of diffusion of cyclopcntylbromide. In ncsiumbromidc (point l5 on this lattcr plateau)is alsoap- nrcdia of low diclectric constant,bromobenzcne appears to proximatelyzcro. and is consistentwith transport-limitedrc- rcact more slowly than it encountcrsthc magncsium.This ilction for thc substitutedbromobcnzenes. Since there is no observationis compatiblewith largevalues for p in thesesol- evidencethat the behaviorof cyclopentylbromidc dilfers in vcnts(Table II). As the solutiondielectric constant increases. THF-HMPA solutionsand in diethylethcr containing cy- thc rate of reactionof bromobenzeneincreases toward that of clopenty'lmagnesiunrbrtrmidc,i the most straightforwardra- cycfopentylbromide. Above ( - J, thc ratio of thc ratc con- tionalizationof the lowcr platcauin Figure5 is that the dii- stants of brornobenzencand cyclopcntyl bromide remains fusionconst^ nt of'bronrobenzcnc is dccreascdslightly in so- constant:k<:,ltrgrlkc-csgqrlr = l.l in THF and in THF con- lutionscontaining high conccntrations ol- Grignard rcagcnts. taining H MPA. This ratio wasconfirmcd as thc ratio of dil'- pcrhapsby complcx formation. fusion constantsby mcasuringthc diiiusion currcnts,i.1, for Reactionof bromobcnzenewith magnesiumthus showsa cachin dc polarogrlrphicreduction: io.cnrr.gr/i,j.c-(.gqtlr = l.l responseto solventsvery similar to that obscrvcdlilr neopentyl oC). (DMF, BuaNBFl,25 Thus for e ) 7, the reactionof bron'ride.iIn diethyl ether, reactionis slightly slowerthan bromobcnzcncwith magncsiumis also mass transport con- transportto the metal surface.As the solutionpolarity in- trollcd.This bchaviorclosely rescmblcs that obscrvedfor ne- crcases.thc rcactionrate increases,and in solventshaving e ) opcntyl bromide.5 7 the rate becomesmass transport limitcd. Thc curvatureob- Figure 5 containsone featurenot observedfor the relative servedlor Hamrnett plots in tetrahydrofuranand tctrahy- ratesof rcactionsof neopentyland cyclopentylbromides:5 two dropyranmay' rcflect thc grcatercontribution of masstransport clcarly dcfined plateausappcar at high dielcctricconstant, one limitationsfor thc ratesof thc slowercompounds in eachscries. for TH F-H MPA mixturesand one fbr diethvl ethercontaininq Figure6 plotsp as a functionof solventdiclcctric constant. As 234 Journal of the AmericanChemical Society I 102:l f January 2, 1980

log (kr/kr) loq (kr/k.) 3Bu2O: I C6Ht2 2,2 h d 8u.o A qr l.u f, ;. I + - 1.4 (n I T(o !'cHr 9 r.o p OCH.O aa I cHs f"" q-cH q.

- ;J o.5 I,",3THF:IHMPA

o.5 o.5 1lI I r

04812162024 ric -m cl ^'< Dielecf Conslont o.s ! cHt a ^^. 4 a a''" g ult p-OCH3O !'CHr l F-igure6. Hammcttp valucsfor thc rcactionof magncsiunrwith substi- tutcd brornobenzenesin dil'l'crcntsolvents. The Hanrrnettplot rn tct- rirhvdropyran(Tl-l P) wasnonlincar. EtlO(RMgBr) denotes dicthyl cthcr containing0.8 M cyclopentylnragnesiumbromide. The error barsarc subicctivccstimatcs of the relativeaccuracies of theseestimates. Figure4. llamrnett plotsfor thc reactionof magncsiurnwith substituted brornobcnzcnes:A, diethyl ether,p - L l; B, tetrahydropyran,0 < p < 0.6;C, tctrahydrofuran,0 < p < 0.4,D, TH F*H MPA (3:l ), p ry 0. Points lor nr- and p-dibromobenzenesin diethylether have been correctcd sta- predlcled lroneporl-controlled tisticalll,forthe presenceof two carbon halogcnbonds by dividingthc rofe in dlethyl cthcr }|i obscrvcdrclativc rates by two; pointsfor thcsccttrrrpounds in TllF have / ,'I rlr.r/bccn correctcd (scc thc text for a discussion). / / ,/ a o ol trJ t.2 t

c o

o o.8 THF:HMPA 3:I 6 x EfrO:P 4tt lU RMgBr o-o.8 Et^O:P r C o o \.'ElzO: ! o.4 N 3:l \o. C6Htz3:l @ o ^BuaO: 6 @ 0ezo -- o.{ 3 o.o ? o.2 t, (cp r) o48121620242A325640 Figure7. There lltivc ratcs ol rcuctil)nol'bromobcnzene with mllgnc\iunt. Dielecfric Constonl rrsl l'unctionof thcreciprocal ol'thc solvcnt viscttsity. Rates werc obtaincd using"constunt surl'ace" techniqucsa at 0 oC,and are itrbitrarill nor- Figure5. Conrparisonof thc rcsponseof the relativerates of reactionof rrurlizcdto thcvirluc in dicthrlcthcr;r'iscositics wcrc lncasurcd rrt0 oC. brornobenzene lnd cyclopentylbromide to thesolution dielectric constirnt l:t1OP.l:l I M RMgllris rr.l:l v:v nrixturc oidicthyl ether and pcntanc indicutcsthat thc lirrmcr ratc becomestransport limited at diclectric contuiningI M cvclopentr lnlrgncsiunr brontide . Thc point indicated -7. b1, constanlsgrcatcr than The solventsenrployed rn thisstudy includcd "*" isthc valuc ol'l'..; prcdicted f'or tnrnsport-controllcd ratcin diethrl (l) (7:3), l]u:O.(2) Bu2OC6H12(3:l). (l) L,t2Opcntanc (4) Et:O cthcr(scc tc\t lbra discussionol'this point). pcntirnc(4:l ). (5) [it2O pentane (9:l ), (6) Et:O.(7) F.t:O0.2 M RMgBr. (r{)TllF-Et:O (2:l),(9) THP, (10) TFIF, ( I I Tl-lF HMPA (3:l (ll) 'l'lll' ) ), tlN4PA(l:l). ( ll) TllF-llMPA (l:3),(1.1) EtrO 0.4M RMgBr. two independentchecks on the conclusion that rzrtesare (15) l:t1O0.lJ M RMgBr,(16) Irtro 1.0M RMgBr.RMgBrdcnotcs (TH cvcl()pcnlylmirgncsiunrbromidc. Solvcnt compositions are v:v.Thc cr- transportlimited in solvcntsof high dielectricconstant F, pcrirncntrrlrcproducibility. as indicatcdfbr thc point dctcrrlincd in THF HMPA. E,tlOcontaining 0.8 M c-CsHeMgBr).First, l:t.C) 0.-lM RMgBr (14).is approximately the same for all points. ratesin the two solventslbr which valuesof p = 0 havebeen measurcd(indicated on the plot by filled circles) fall on a straightline passing through the origin.Second, nonc of the the dielectric constant increases (and, presumably, as the rates solvcntsexamined yiclds rates which lhll abovethis line. Both of rcaction increase), the value of p smoothly decreascs. Sincc obscrvationsarc compatiblewith the hypothesisthat the line the approximatelyzcro valuesobservcd for p in high dielectric reprcsents an uppcr limit setby the masstransport of bromo- solventshave beenidcntificd with transport-controlledreac- bcnzcne.By extrapolatingthis linc to low viscosities,it is tions,it appearsthat the decrcascin p in going from dibutyl possibleto predictthat the transport-limitcdratc that would cther-cyclohexaneto diethyl ether reflectsthc proximity ol' be observedlor bromobenzcnc in a solvcnthaving thc viscosity thc rcactionratcs to the transport-lirnitcdrzrtc.-ll oidiethy'lcther(4 = 0.-12cP. 4-r = -l.l cP-r)rr wouldbc fastcr Figurc7 showsthe ratc of reactionol'bromobenzene with than thc rate actuallyobserr,'ed in diethyl ether by a l'actorof magncsiumin severalsolvents. obtained using thc "constant l.ft This valucis in goodagrcemcnt with cstimateso1'the same surlirce"kinctics technique describcd clscwhcre,a.s pltttted vs. nurnberl'rom two scparirtcsourccs: thc factor scparatingthe thc reciprocalof thc viscosityof the solvent.Thcse data providc ratc ol'rcactionof bronrobcnzcncin diethvlether from thut of' Whitesides et al. f Reaction of Substituted Aryl Brontides with Magnesiunt 235 an alkyl halideof approximatelythe samc molecularweight (and thus, diffusion constant)which reactsat a transport- controlledrate in thissolvent (e.g., kc-crlten,./ft1'011.s," = 2.l)a and the difference in the ratio of rates in Figure 5 betwecn 2'o2 diethyl ether and solventsin the plateau regions th.t. ;;;; = "f = (ArCl) (for R kCoH,B.lkr-crg;1Br, RrHn rrH,ren/Rr,.t2o2.3 and Elr0 RE,.g RMsBr/REtzo= 1.7). Statistical Corrections to Rates of Reaction of Dibromo- P r.o benzenes.Table I containsrelative rates of reactionof I .3- and 1,4-dibromobenzenewith magnesiumin diethyl ether and in tetrahydrofuran. Observed rates in the former solvent were 0.o correctedstatistically for the presenceof two equivalentcar- bon-brominebonds by divisionby two; ratesin the latter sol- vent were not statisticallycorrected. It was possibleto decide -4.0 -3.O -2.O -r.O if the observedrates should be statistically correctedonly after o.o establishingwhether the reactionsof the aryl dibromideswere log kobtd/ktl transport limited. In diethyl ether, evidencesummarized above Figure8. Plot of'log (/iobsa/k1l)(frobsd is the observcdratc constant,ltl hasestablished that thesereactions are not transportlimited: is thc transport-limitedrate constant derived lrom Figure7)vs. p for aryl the aryl dibromidespresumably encounter the magnesium bronridcsin scveralsolvents(open syrnbols)and for arylchloridesin dicthyl surfacemany times beforethey react. In tetrahydrofuran,the cthcr (fillcdsymbol). Thc dottedlincs reprcsent plausiblc cxtremcs for rate of disappearanceof the aryl mono-and dibromidesis de- 1.rat valucs,rt1"u'd/k'l ( 0.1.Solvcnt compositions are dctailed in Tablc terrnined by transport to the magnesiumsurface, and is inde- il. pendent of the number of carbon bromine bonds present. Statisticalcorrection is not appropriatein this solvent.The observationthat the statisticallyuncorrected rates for m- and In lesspolar solvents-diethyl and dibutyl ether and dibutyl p-dibromobenzenein tetrahydrofuranseem to fall slightly ether-cyclohexane-the observationof linear Hammett plots abovethe adjacentpoints in the Hammett plot of Figure4 is with significantp valuesestablishes that the reactionsof aryl compatible with the inferenccdrawn from the apparent cur- bromideswith magnesiumare not transport limited. Inter- vature in this plot,and from thedata in Figure6, that reactions pretation of thesep valuesin terms of charge in the transition in this solventstraddle the regionbetween transport-limited stateis complicatedby the proximity of the ratesfrom which and non-transport-limitedregimes. Ii the reactions were thcy are derivedto the mass-transport-limitedregime. Phenyl transportlimited, the statisticallyuncorrected ratc shouldfall bromide reactswith magnesiumin diethyl ether at approxi- on the Hammett plot; ii the reactionwere not transportlimited, mately the same rate as neopentylbromide:a that is, at ap- a statisticalcorrection of two shouldbe required.In fact, the proximatelyone-half the expectedmass-transport-limited rate. uncorrccteddata seemslightly too high,while data corrected Sincethe proximity of theserates to the mass-transport-con- by dividing by two would be too low. trolled limit would be expectedto decreasethe magnitudeof Carbon-halogen bond breaking is irret'ersible. The overall p. the observedvalues of p should be consideredminimum rate-determiningstep for disappearanceof aryl halidesin di- values.when discussingthe charge distribution in a hypo- ethyl ether and other solventsof low polarity might, in prin- thctical, non-transport-limitedtransition state. ciple, involvea reactionof a reversiblyformed intermediate It is possibleto get a qualitativepicture of the behaviorof in which the carbon-halogenbond was broken (e.g.,an aryl 1rin the regimeclose to transport-limitedrates using a proce- radical,or a surflicearylmagnesium compound). Reaction of dure basedon Figure 7. For eachsolvent system in this figure, a mixture of bromobenzeneand o-iodotoluenewith magncsium we estimatedthc proximity of the observedr',1. ftobsdto the to approximately 50o/oconversion, followed by quenching of transport-limitedrate ktr in that solvent:the latterquantity the reactionmixture and examinationof the residualaryl ha- may be estimatedat any valueof 4-r from the line proposed lidcs,showed that no iodobenzeneor o-bromotoluenehad been to representtransport-limited reaction. Thus, for example, formed (15V,twould have beendetected). Thus, cleavageof 1'bsd/fttl= 0.1I for Bu:O. Figure8 plotsthese data. Although thc carbon halogenbond is probablyirreversible.la it appearsthat the apparentvalue of p decreasesrapidly for valueso11'rb'd/ktl > 0.l, we do not havethe data lor 1.bsd/fttl Discussion < 0.1 which would be requiredto extrapolatep to a reliable The objectiveof thesekinetics studies was to establishthe valueat ratcssufficiently slow as to be uninfluencedby their nature of the rate-determiningtransition state(s) for disap- proximity to transport-limitedvalues. Attcmpts to slow the pearanceof aryl halidcsby rcactionwith mctallicmagnesium ratcsexperimentally by addingquantities of hydrocarbonslcd in cthcrcalsolvents, The rangeof possiblelimiting structures to precipitatesor two-phascliquid mixturcs.A valueoi p is (l-8) is similar to that discussedpreviously for reactionsof availablefor aryl chlorides in diethyl ether which is far re- = 1 RFtr 5 R+ nrovcdfrom kob\dI ku I , but the relevanceof this datum to reactionsof aryl bromidesis unclear.Fragmentary evidence 2 tll.tSr't'Mg. 6 R dcrivcd from comparisonsof rate-structureprofiles for reac- 3 tRBrt= 7 R---Br tionsof alkyl bromidesand alkyl chloridessuggested that re- ," "t nction rateslor the latter group of compoundswere lesssen- Mg. sitiveto changesin alkyl group structurcthan the former by 4 R- 8 RMg'X approximatelya l'actorol'4:a if thc samedifference in scnsi- alkyl halides,aalthough a backsideS52 attack by a surface tivity holdsl'or aromatic halidcs,thc valueof p for slowly re- nragncsiumatom on carbon is prccludcdfor aromatic sub- actingaryl chloridcsrnight bc much srnallcrthan that for a stnrtes.In polarsolvcnts (e > 7). the rate of reactionof aryl (presentlyhy'pothetical) group of slowly reactingaryl bro- brornidesis transportlimited. The reactionof iodobenzcnes midcs.r5 is apparcntlytransport limitcd cven in diethylcthcr (r t 4): [:vengivcn prcscntunccrtuinty conccrning thc significancc 1t= 0 for this systcm,and the ratc of reactionof iodobenzcnc of p for dicthy'lor dibutylether.it is possiblcto intcrprctthesc itsell'lalls on the lineidentified with transport-lirnitedrates.a valucs to cxcludc scvcral of' thc nossibletransition-state 236 Journalof the AmericanChemical Society I 102:l f Januor,v*2, 1980

t.o p-Br i [... a .t o-F ,-tul m-Cl t't-" .' or-.,."-t' l- o.8 P-clo l-u''3ao q-cFr qr ar_a"-ta-oar, ,-i,,Ff[''' - p-OCHg c ) + L-o.. o.6 c) q-cF o.4

@ / m-CF- o I o.4 @ P-cl (J fJ, ..- O-r o.2 p-F " -o.8 @ !-ocH3a ; ,

I a D-8r P-H E' P-H o.o O' oll -0.6 o o.o p-OCH3 (D !-cFr o tr) P-cHl t -o.2 o !-cHr ro -o.2 n-cHs .t jl-oCH3 m-C Fa -o.4

(D

-o.2 0.o o.2 o.4 o.6 o.8 x m -OCH3l -o.? e'l o log (korsr/ka.rurr), ArBr + BuoSnH -o.o T'?-H!

n-At"ll Iigure 9. Cornplrrisonof thc relativerates of reactionof substituted m-CHa bronrobcnzcneswith ntagnesiurnand with tri-n-butyltinhydridc: A. Tt{[]: o.2 --o.2 p-cHr B. dicthylcthe r. I -oo-co-Cl m -Cl structuresrepresented by 1-8. Since p has a significant positive o.o -.,| O m-CF- value,the transitionstate does not resemblethe starting ma- .:,'jl,:,: 5 terial, and I can be discarded.The magnitude of p seemstoo -o.2J1 largeto be compatiblewith physisorption,2. The sign of p is incompatiblewith an intermediatearyl cation, 5. Without -?.o -r.8 -t.6 knowing an accuratemagnitude for p, it is difficult to exclude carbanionicstructures (4). Nonetheless, since the largestvalues ,y, observedare similar to those for tin hydride reduction,and considerablysmaller than that estimatedfor reactionsgener- ating aryl anions(p = 6, Table II), the magnitudeof p seems Figure l{). Rclativcratcs of'rcaction ol'substitutcd brtlmobcn/e nes its il (l-ootnotc too small for a fully formed aryl carbanion4. A rate-deter- l'unctionol'the ir hall-wavcrcduction potcntills t, TableI): ,'\. C(,ll | B dicthrI cther; C. Tl-lIr H M PA (3:l). mining stepinvolving an intermediatein which the carbon- lluro r:(-l: ). magnesiumbond is partially or fully formed (8) is unlikely', both becausethis transitionstate bears a large negativecharge (lrastmanor J. T. f]aker)wcrc uscd.[,nlcss otheruisc spccil'icd. thc value for p on carbon and would be expectedto show a large reactions\\'crc run usingthe Eastmitnor.l . T. Bitkcr magne\iunt and becausecleavage of the carbon-bromine bond appearsto turnings.Rcagcnt gradc dicthl l ethcr. di-n-but.'"1 cthcr. tctrahydro- be irreversiblc. luran, and tctrahvdropvranwcrc distillcdunder arg()n frorn lithiunr It is morc difficult to differentiatebetween reactions leading rrluminumh1'dridc. crrlciurtt hrdridc. or disodiuntbcnzophcnonc di- to the three rcmaininglimiting structures-electron transfer anion.2-Butunol was drstillcd I'rrlnt ntrtgncsiutn l-butrlridc. Xrlene from magnesiumto aryl bromidegenerating the radicalanion (a nrixturcol'istltrcrs) und crclohcxanclvcrc distilled l'rttnt sodiunt. 3, bromine abstractionby magnesiumforming an aryl radical l-lcrarlcthl lphosphorlnridcu'us distillcd f-rttntsodiunt undcr vacuuttt (bp 65 oC. 0..1Torr).r(' Munipulation o['solutions lor Cirignardlbr- 6, and insertionof magnesiumdirectly into the carbon-bro- nrationor tri-l-butt ltin hidridc rcductionslirlloucd slandard incrt mine bondof an adsorbedaryl bromide7-on the basisof the irtmosphcreproccdu rcs.lT Elcctrochcnr iclr l nrclrsurcmcnts n'ere curricd evidencc.The ratesof reactionof aryl bromideswith available out usinga PrincctonApplicd ResearchModcl 17.1Apolarogrephic nragnesiumcorrelate equally well with ratesof bromine ab- ana l1'zc r. straction by tri-n-butyltin radical (Figure 9) and with po- StandardC'onditions for ('ompetitire Reactionof Substituted'\rr I larographic reduction potentials(Figure l0). A concerted Halideswith l\lagnesiumin Ether.Sincc thcrc arc signif'icuntvariutions inscrtionwould presunrablyshare the characterof halogen in thc ratc of consuntptionof organic halidesin (irignurd rcrtction: abstractionand electrondonation, and would also be expected duc to rnagncsiunrrcactivitr. solvcnt e f'l'ccts. and halidcrcitctivitr. ()rgirnte to correlate.The abstractionof the bromine atom from an aryl it $as conl'cnicntto vlrrr thc alllountsol' both ntagnesiutnitnd various trrtctltblcnttc bromide by tri-n-butyltin radical is probably a good model for hirlidcsuhich ucrc uscdin thc runsto achicvcl ol rcaction.Thcse vuriations hud no cilcct on thc rclativeratc c()nstants atom abstractionby a metal surface.Whether polarographic obtaincd.ln allcasesa thrcc-to sevcnloldcxccss ol'tnugncsiunt was reductionadcquately models single-electron transfer is less prcscntat the bcginningof'thc rcuction.Tr picall,v.to a thrcc-ncckcd. polarographicreduction clear,since the dctailcdmechanism of -50-m[-.round-bottonrcd llask containing a nltgnctic stirringbar u'us of organichalides is still not established. addcd0.llt 3.0g (0.00tt0.12 g-atonr) of ntitgncsiunr.The anr()unt ol rnagncsiurnuscd dcpcnded on thc solvcnt.thc halidc rcactivin'.rtnd Experimental Section thc nunrbcrof'halidcs collrpcting in eachrun. In gcncral.f'or e xpcri- (Jeneral.Magnesiurn powdcr (Mallinckrodt), triply sublimcd mcntsinvolv'rng arrl halrdes.3.0g (0.12g-rrtont)of'ntagncsiunt was magnesiunrturnings (Dow). itnd reagent grade magncsium turnings usedlbr I 0g (S 6 rnntol)ol'eacharylhalidc in allsolvcnts.Thc flask Whiteside,s et al. f Reactit.tn oJ'Sub.rtituted Arl,l Bromides u,ith Magne.;iurtt 731

Table Ill. Effectsof Changcsin RelativeAmounts of r.o Magnesium,"Aryl Halides.6and Initial MagnesiumBromide Conccntrations''on a ReprcscntativeRatio of Rate Constants reac- tiond Mel MgBr2/ 6-t2 t3-t5 _t9 no. )ArX" )ArX' (k.,lk)h comments ' x -j= f :O i I t7,t8 I 0.2-s 0.5 0.55 G| 2 0.50 0.5 0.56 x l r.0 0.5 0.57 -',1 1.0 0.0 0.,58 nosurface cleaning 5 1.0 0.0 0.-54 nosurfacc cleanrng. wetcthcr / 6 3.0 0.5 0.56 7 3.0 0.5 0.61 o.o 5.o to.o 8 3.0 0.5 0.61 magnesiumpowder 9 3.0 0.5 0.63 triplysublimed mag- Equiv Mg/Equiv ArBr nesium Figure I l. Effcctsol changesin relativeamounts of magnesiumto aryl l0 3.0 0.0 0.58 nosurface cleaning bronridcsin solution(equiv Mg/equiv ArBr) on the relativerates of rc- il 3.0 0.0 0.54 surfacecleaned, rrction(k2l k t) of p-bromotoluene(2)and bromobenzene( | ) in ether.Thc saltsremovedc ;rointsin thc grapharc nunrbcrcdto correspondto the rcactionslisted in t2 3.0 1.0 0.57 Tlblc I l. l3 4.0 0.5 0.61 l4 4.0 0.5 0.62 l_s 4.0 0.5 0.61 trirnsfcrringapproximately 0.5 mL of the reactionmixture by cannula r6 8.6 0.5 0.54 inttr a vial, capped with a rubber septum stopper,containing a t7 r0.0 0.5 0.59 qucnchingsolution ol I N hydrochloricacid and ice. lf thc rcaction l8 r0.0 1.0 0.57 solvcntwas water soluble(TH F or H MPA), pentanc(0.5 mL) was l9 10.0 0.0 0.63 surfacecleaned, ldded to extract the unreactedhalidcs: extraction of unreactedhalides saltsremovedc Irndinternal standards was found to be essentiallyquantitative. The organic laycr was separatedand analyzcdby GLC. A least-squares 'Grignard reagentgrade magnesiumturnings were usedunless plot of In ((.r,1Ctolvs. In (C!lC:01yielded ktlkt. Sinceonly the h otherwiscspecified. Thcsereactions werc run in dricd etherusing rclativeamounts of the c

"selective Organic Transformations",Vol. ll, B. S. Thya- t)iffusioncurrcnts (ia) u'crc ptcasurcdttsing rt dropping lllcrcur\ (16) L. A. Singer in garajan, Ed., Wiley-hterscience, New York, 1972,p 239 ff; O' Simamura, dc polarogltnl as dcscribcdpr5 i- clcctrodc(DM Il). rccordingthc Top. Stereochem.,4,1 (1969);R. W. Fessenden'J. Phys. Chem.,71,74 ri ()ust\. (1967); P. H. Kasai and E. B. Whipple, J. Am. Chem. Soc., 89' 1033 (1 967) Acknowledgment.Professors John Deutch ( Massachusctts (17) J. E. Deutch,J. F. Garst,C. L. Hill,H. R. Rogers,and G. M Whitesides,un- Instituteof Technology)and Paul Rys (E. T. H., Zurich) oublished observations. ( 18) D. J Patel,C. L. Hamilton,and J. D. Roberts, J. Am. Chem. Soc', 87 , 5144 provideduscful suggcstions conccrning the problcmof statis- (1 965) iical correctionsto diffusion-limited rcactions of aryl di- (19) F L. Lambert,J. Org. Chem..31,4184 (1966). (20) P. Zuman, "substituent Effects in Organic Polarography"'Plenum Press. bromides. New York, 1969, "The Elucidationof Organic ElectrodeProcess', Aca- demic Press.New York, 1969. (21) Czech. Chem. Commun., 25,3225 (1960). Referencesand Notes P. Zuman, Cottect. Q2\ J. W. Sease, F. G. Burton,and S. L. Nickol, J. Am. Chem. Soc., 90' 2595 (1968). (1) supported by the National Science Foundationthrough Grants GP 28586X, (23) W. W. Hussey and A. J. Diefenderter, J. Am. Chem. Soc., 89,5359 GP 14247, MPS-74-20946, and 77 11282-CHE' and through grants to the ('1967). M.l.T.Center for MaterialsScience and Engineering. (24) Pollardand J. V. Westwood, J. Am. Chem. Soc, 88, 1404 (1966) (2) TexacoFellow, 1975-1976. D. R. (25) Fraserand R. N. Renaud,J. Am. Chem. Soc., 88,4365 (1966). (3) NationalInstitutes of Health PredoctoralFellow, 1966-1969' R. R. and G M' (26) H. G Kuivila,Acc. Chem. fres., 1, 299 (1968);D. J. Carlssonand K. U. In- i+i H. n. Rogers.C. L. Hill,Y. Fuiiwara,R. J. Rogers,H. L. Mitchell, gold, Am. Chem. Soc., 90, 1055 (1968);H.G. Kuivila, Synthesis'2,499 Whitesides, J. Am. Chem. Soc., accompanying paper in this issue' J. (1970). (5) H. R. Rogers,J. Deutch, and G. M. Whitesides,J- Am. Chem Soc', pre- (27) H. Davis,Jr., J. H. Gleaton,and W. A. Pryor,J. Org. Chem.,42,7 (1977). ceding paper in this issue. W. -2 32, Studies of tin hydtide reduction of bridgehead aliphatic halides have also (6)' ' Repreientative values of perlinent reduction potentials fo]low:Ph^Br, -2'56; interpreted as indicating little or no charge separation in the transition Phi, -1.62; n-BuBr,-2.27 (SCE,75"k dioxane,EtaNBr);/ PhCl, been -2.09; R. C. Fort Jr. and J Hiti, J. Org. Chem., 42, 3968 (1977)'- PhBr,-2.Q7', Phl, -1.59; n{sHrrBr, sec{sHr tBr,-2 12; t8uBr, state: (28) A. Pinto, Am. Chem. Soc.. 94, 7390 (1972). -1.91, vs. SCE in Me2SO (MeaNPFo).8Further examples are discussed A. A. Zavitsasand J. J. (29) W. Danen and D. G. Saunders,J. Am. Chem. 9oc.,91,5924 (1969). by M. R. Rifi in "Organic Electrochemistry", M. M Baizer, Ed , Marcel C. (30) bromide is insoluble in diethyl ether containing Dekker, New York, 1973, p 283; F L. Lambertand K. Kobayashi,J Am' cyclopentylmagnesium TMEDA,THF, or high ()50 % concentrationsof hydrocarbons.Similarly, Chem. Soc., 82,5324 (1960). ) 1,2-dimethoxyethane(glyme) and higher homologues, as well as THF (7) A. J. Fry, "synthetic Organic Electrochemistry",Harper and Row, New containing )107o hydrocarbon, were found to precipitate the product York, 1972,P 170. reaqent (8) A. J. Fry and R. L. Krieger, J Org. Chem., 41,54 (1976). Grignard (31) and R M. Jones,J. Org Chem.,24, 1685 (1959). (9) The polarographic reduction of organic halides is reviewed by c. K Mann R E Dessy (32) D. Chem. Rev.,75,755 (1975):the quantitativeform expected and k. t<.garnes, "Electrochemical Reactions in Nonagueous Systems", C. Johnson, .l970, plots involvingnear-diffusion-limited rates is not clear. Marcel Dekker, New York, Chapter Vl. There is no polarograpnrc for Hammett (33) The point representingEt2O pentane (4:1) containing 1 M RMgBr was evidence for the independent existence of radical anions of either simple from relative rate data and rate vs.4-1 data for cyclopentyl aryl or alkyl halides. calculated The measured in Et2Ocontaining 0.8 M RMgBr (p = 0.1 + 0.2) (10) For evidence concerningthe lifetimeof alkyl halide-radicalanions, see J. bromide.s 1,r be very close to the for Et2O-pentane (4:1) containing 1 M RMgBr: F. Garst, R. D. Roberts,-andJ. A. Pacifici, J. Am. Chem. Soc', 99, 3528 should 1r of both solutionsare sufficientlyhigh to ensure a (1977),M. C. R. Symons, J. Chem. Bes' (S), 360 (1978). the dielectricstrengths rate in each (cf . Figures 5 and 6 and ref 5). Reaction in (1 1) Evidence for transient aryl halide radical anions in the vapor phase is, In transport-limited Chem' THF is indicated in Figure 7 as transport limited. Although the curvature fact, firm [K. D. Jordan,J. A. Michejda,and P D. Burrow, J Am in the Hammett plot for this solvent suggests that not all of the substituted Soc,. 98,71S9 (1976)1.but it is not clear that the species observed are bromides react at a strictly transport-controlled rate, the conclusion analogous to the species which would be obtained by one-electron re- aryl reaction of bromobenzene itself is transport controlled is not likely duction of alkyl halides:aryl halide radical anions have only been detected that in error in the 2A2 state (which has a node in the HOMO at the carbon-halogen to be much 28r (34) which would not lead to halogen interchange might, in principle, bond), and not in the state (which places negative charge in the car- Cleavage place. lt would, however, seem improbable a priori, and would be bon-halogen o- orbital).For related, indirect,evidence for chlorobenzene take difficult to test for experimentally. radical anion, see J. M. Warman, M. C Sauer, and G. R' A Johnson, J' exceedingly (35) recent study of the reaction of aryl halides with nickel(0) complexes has Chem. Phys., 5'1,3477 (1969). A generatedthese values of p(Arl) = *2.0: p(ArBr) = i4 4',p(ArCl) = (12) T. Yoshino,Y. Manabe,and Y. Kikuchi, J. Am. Chem. Soc.,86' 4670 (196a); 1t: +5.4 (T. T. Tsou and J. K. Kochi, J. Am. Chem. Soc., in press).This reaction D. Seyferth,Prog. lnorg. Chem.,3, 150 (1962); B. Mechin and N Naulet' has been interpreted as involving an electron-transfer step. The fact that J. Organomet. Chem., 39,229 (1972); H. M. Walborsky and M' S Aronoff' significantlysmaller value for p(Arcl) for reaction with ibid., 51,31 (1973).conversion of vinylic bromidesto organolithiumre- we observe a magnesium still does not distinguish between inner-sphere electron transfer agents also occurs with retention of stereochemistry: D. seyferth and L. (haiogen and outer-sphere electron transfer, because rate Gi Vaughan,J. Am. Chem. Soc., 86, 883 (196a);G. M. Whitesides,C P' abstraction) profiles for the two types of reactions are probably linearly related. Casey,and J. K. Krieger,ibid.,93,1379 (1971). structure Barber and G. M. Whitesides J. Am. Chem. Soc., following paper (13) C. Ruchardtand H. Trautwein,Chem- Ber-,95,1197 (1962)' Cf . J. J. in this issue;B. Durham,J. F. Endicott'C.-L. Wong, and D. P. Rillema,ib'd.. if ai H. W. H. J. Bodewitz,C. Blomberg,and F. Bickelhaupt, Tetrahedron,3l, (1979) 1053 (1975);C. Blomberg, J. Organomet.Chem-, 45, 1 (1972)' and ref- 101.847 (36\ HMPA has been suggested to be carcinogenic: J. A. Zapp, Jr . erences cited in each. Caution 422 ( 1975). (15) H. L. Goeringand F. M. McCarron,J. Am Chem-Soc., 80, 2287 (19581' Science.'190, (37) "Organic Synthesesvia Boranes", Wiley, New York, 1975, O. Reutov, Butt. Soc.Chim. Fr.,1383 (1963);G. R. Buske and W. T. Ford, H. C. Brown, 9. J. Org. Chem.,41, 1998 (1976). Chapter