《有机化学》课程教学资源（文献资料）A Kinetic Study of the ortho-Claisen Rearrangement.pdf_大学文库

July 5, 1958 KINETICS OF Ortho-CLAISEN REARRANGEMENT 3277 Strong interaction of this nature is possible since the carbons of the allyl group may lie in a plane directly over the aryloxy grouping so that the acarbon of the allyl group is over the oxygen of the aryloxy moiety, the P-carbon is over the 1-position of the ring, and the y-carbon over the 2-position. This places one terminal carbon of the allyl group over the oxygen from which it breaks away and the other over the o-carbon to which it becomes bonded. This complex must be very short-lived if it is to maintain its orientation. The substituent data are explained if structure I1 contributes more to the resonance hybrid than 111-a positive charge which is stabilized by electron donation is placed on the aromatic ring during reaction and as a final stage, if equation 2 is to apply, a negative charge is cancelled at the position meta to the substituent requiring electron withdrawal. That I1 actually would contribute more than I11 is indicated by the fact that the difference between the ionization potential of the benzyl radical32 and the electron affinity of the allyl radical33 is about 17 kcal./mole greater than the difference between the ionization potential32 of the allyl radical and the electron affinity of the benzyl radical.33 Although this comparison is not precise because the actual system involves a phenoxy radical rather than a benzyl radical, it is likely that the comparison is justified since the electron affinity of phenoxy radical34 is even less positive than that of benzyl radical by 14 kcal./mole. Finally, this latter mechanism is supported by an analogy to the Diels-Alder reaction for which a charge transfer complex mechanism has been postulated by W0odward.~5 Like the (32) D. P. Stevenson quoted by A. Streitwieser, Jr., Chem. Reus., (33) N. S. Hush and K. B. Oldham quoted by H. 0. Pritchard, ibid., (34) N. S. Hush quoted in H. 0. Pritchard, ibid., 62, 529 (1953). (35) R. B. Woodward, THIS JOURNAL, 62, 3058 (1942); R. B. 66, 571 (1956). 63, 529 (1953). Woodward and H. Baer, ibid., 66, 645 (1944). Claisen rearrangement, the effect of substituents on the Diels-Alder reaction of l-(p-X-phenyl)-1,3- butadienes and maleic anhydride has been found to be most suitably correlated by use of the u+ constants and a small, negative p.23.36 The existence of a polar intermediate or transition state in the Claisen rearrangement is demonstrated not only by the substituent effects but also by the preliminary results on the effect of solvent (Table VI). A semi-quantitative treatment of the data is not possible since the dielectric constants of these solvents have not been measured at the temperature of rearrangement, and the change of dielectric constant with temperature is different for different solvents. However, it is encouraging that the solvent of lowest dielectric constant at ordinary temperatures (n-octane) yields a rate onethird to one-seventh that obtained with the other solvents, and that the addition of a salt to Carbitol (which should increase the dielectric constant) increases the rate. The solvent rate effect observed for the Claisen rearrangement is similar in magnitude to that for the Menschutkin reactions of methyl iodide in benzene-nitrobenzene mixtures, 37 a reaction which is most definitely polar in nature. There are, therefore, at least three reasonable mechanistic explanations for the substituent and solvent effects observed in the Claisen rearrangement. Unfortunately, at present, there is not enough experimental information available to decide among these possibilities. (313) The effect of a y-methyl group in the allyl portion of the ether (footnote 30) can be explained as being due to a larger contribution by structure I11 to the hybrid. The additional methyl group should tend to stabilize 111. (37) H. C. Raine and C. iT. Hinshelwood, J. Chem. SOL, 1378 (1939); K. J. Laldler and C. N. Hinshelwood, ibid., 858 (1938). COLUMBUS 10, OHIO [CONTRIBUTION FROM THE DEPARTMENT OF CHEMISTRY OF THE UNIVERSITY OF I IS CONS IS] A Kinetic Study of the ortho-Claisen Rearrangement' BY HARLAN L. GOERING AND ROBERT R. JACOBSON RECEIVED JANUARY 27, 1958 The relative rates of the ortho-Claisen rearrangement of allyl phenyl ether, fifteen m- and p-substituted allyl phenyl A dilatometric The relaThe relative reactivities of ethers and a-, 0- and y-methyallyl phenyl ether at 185 and 197" in diphenyl ether have been determined. method for following the reaction accurately using low concentrations (about 0.1 M) of substrate was developed. tive rates of rearrangement of allyl p-cresyl ether in twelve solvents also have been determined. the series of p-substituted allyl phenyl ethers can be correlated by the CT+ substituent constants. Introduction In many respects the ortho-Claisen rearrangement2 is similar to the intramolecular (SNi') rearrangement of allylic ester^.^ Both of these reactions are first-order intramolecular processe~.~,~ (1) This work was supported in part by the Office of Ordnance Rcsearch, U. S. Army, and in part by thP Research Committee of the Graduate School with funds given by the Wisconsin Alumni Research Foundation. (2) D. S. Tarbell in R. Adams, "Organic Reactions," Vol. 11, John Wiley and Sons, Inc., New York. N. Y., 1944, Chapt. 1. (3) (a) H. L. Goering and R. W. Greiner. THIS JOURNAL, 79, 3464 The relative positions of the atoms in the reactants and products are the same for the two reactions and in each case the over-all reaction can be summarized as a six-membered cyclic process as illustrated by I and II.4 In the Claisen rearrangement (1957); (b) H. L. Goering, J. P. Blanchard and E. F. Silversmith, ibid. 76, 540b (1954); H. I. Goering and E. F. Silversmith, ibid., '77, 1129 (1955); (c) unpublished work of R. H. Jagow and M. M. Pombo. (4) It recently has been shown with 0'5-labeled esters that in the SNi' rearrangement of allylic esters the carbonyl oxygen atom in the reactant becomes the alkyl oxygen atom in the product as illustrated by 11; W. E. Doering, private communication (1955); E. A. Braude and D. W. Turner, Chemirlvy f-? Industry, 1223 (1955)

3278 HARLAN L. GOERING 4ND ROBERT R. JACOBSON Vol. 80 (I) the initially formed dienone is converted to the corresponding phenol. there is evidence that there is some covalent bonding between the allylic carbon atoms and the oxygen atoms in VI. It has been suggested* that similar intermediates may be involved in other I1 It would appear that the stereochemical relationship between reactant and product should be the same for the two reactions, however, there is evidence that this may not be the case. It has been de~nonstrated~~J~ that in the rearrangement of trans-a, y-dimethylallyl esters (HI), the configuration of the asymmetric carbon in the product is opposite that of the asymmetric carbon in the reactant, ;.e., in this system the product and reactant are enantiomers as illustrated below. On the other hand, it has been conclude@ that in the H 13 li / H’ ‘11 11 rIIa IIlb Claisen rearrangement of optically active trunsa, y-dimethylallyl phenyl ether (IV) ,6 the configurations of the asymmetric centers in the reactant and CHaCHCHzCHCHa I product (V) are the same. If this conclusion is correct, the stereochemical relationship between reactant and product differs for the two cases. In another problem the relative configurations of IV and V are being re-examined to determine whether this apparent discrepancy is real. Considerable information concerning the timing and nature of the electronic shifts in the SNi‘ rearrangement summarized by I1 has been presented in earlier papers3 It appears that an intermediate VI (an “internal ion-pair” intermediate according to Winstein’s classification’) is involved in this reaction as follows. As indicated previouslyaa (5) H. Hart, THIS JOURNAL, 76, 4038 (1954). (6) E. R. Alexander and R. W. Kluiber, ibid., 13, 4304 (1931). (7) S. Winstein, E. Clippinger, A. Fainberg, R. Heck and G. Robin son, ibid., 78, 328 (1956). I K \,- I 12 intramolecular processes including the Claisen rearrangement. In order to obtain inforniation concerning mechanistic details of the ortho-Claisen rearrangement (I) we have examined the effects of substituents and variation of solvent on the rate of rearrangement. The results of this investigation are presented in this paper. The rates of the ortho-Claisen rearrangement of a few aryl allyl ethers in the absence of solvent have been reported previously.”l” Kinetic studies of the rearrangement of allyl /]-cresyl ether in diphenyl ether lo and allyl 2,l-diinethylphenyl ether in diethylaniline“ also have been described. In the latter two cases rather high concentrations of substrate were used (5-335; by weight of the reaction mixture) and the reactions were followed by determination of the amount of phenol formed by quantitative acetylation. This method is liniited to non-hydroxylic solvents and probably could not be used with low concentrations of substrate. In the present work a dilatometric iiiethotl was developed which can be used to follow reactions at temperatures up to 200”. Previously dilatoiiietry has been used to follow reactions only at ternperatures near room Tletails of this method are included in the Experimental section. \Vith it the ortho-Claisen rearrq+ncnt can be followed with a high degree of accuracy at teniperatures of iS3-800” using low concentratioiis of substrate (about 0.1 111). lye have used this niethotl to deterniine (a) the relati1.e reactivities of allyl phenyl ether and eighteen substituted allyl phenyl ethers and (b) the relative rntes of rearrangenicnt in twelve solvents. Experimental Allyl Phenyl Ethers.-Except as iiotecl bel(^^ all of tlic ethers were prepared bj- the following tnethotl which is u modification of the method used by Claiseii.I3 A solutioti of 0.2 mole of plieiiol, 0.22 inole of ally1 brotnitlc atid 0.22 mole of potassium carbonate in 50 1111. of drl- acetoiie W:LS refluxed for 8 hours. hfter cooling, the reictimi inisture was diluted with 250 nil. of water aiid extracted with three 35-ml. portions of ether. The organic layer WIS ivashetl first with 105; aqueous sodium hydroside aiid then with water and dried over magricsiurn sulfate. .lfter reinoviil of the solveiit the residue was fractioiiatcd under rcdueetl (8) I) J. Cram, tbid , 74, 2129 (1952); 75, 332 (10;iX). (9) €1. Schrnid and K, Schmid, H~la. Chzin. .4c/ii, 35, 18i!l (1932). (10) J. F. Kincaid and D. S. Tarbell, 7‘rirs JOIJRNAI., 61, 30% (11) 1’. Kall,erer and H. Schrnid, 11~1:’. i’hiiii. tlclu, 40, 13 (1‘337) (12) (a) J. S. Brbnsted, el (IL, THIS JULIRNAI., 49, 2584 (liI27); 61, 428 (l!J?!I); (h) L. K. J. Tong and A. 12. Olson, ibid., 66, 1701 (19.43). (13) L. Claisen and 0. Eisleh, .41n>~, 401, 21 (1913). (1039)

July 5, 1958 KINETICS OF O?'thO-CLAISEN REARRANGEMENT 3279 Substituent P-NH2 P-OCzH, p-OCH3 P-CHB p-c1 p-Br None p-CHO P-COOCsH, p-COCH3 P-CN P-NOz WZ-OCH~ m-SOz p-CH3 -(-CHJ a, -,-Dimethyl TABLE I PHYSICAL PROPERTIES OF SUBSTITUTED ALLYL PHENYL ETHERS Obs. b.p. Lit. b.p. OC. bIm. Obs. ?$~SD OC. Mm. Lit. nb 97.2-97.4 1 1.5679 136 11 70.0-70,5 0.1 1.5249 119-120 13 119 11 M.p. 44.2-45.0" . . M.P. 39-40' 100.0-100.5 9 1.5157 65 4 1,5199 (200) 97.0-97.3 10 1.5348 106-107 12 110.0-110.1 10 1.5583 126 14 67.5-67.6 10 1.5196 73 11 1.5190 (26") 100.0-100.1 0.6 1.5258 156 10 106.0-106.5 2 1.5069 142 10 89-90 0.6 1.5525 146-147 10 1.5432 (45") 94.0-91.5 .3 M.p. 43.6-44.1" . . ALP. 43" 105-106 .4 1.5789 160 12 66.0-66.1 .5 1.5263 125-126 15 92.2-92.3 .6 M.p. 32-33' 136-137 8 M.p. 31,532' 75.2-75.8 10 1.5136 70 8 1.6168 (20') 87.1-87.5 8 1.5183 95-98 12 1.5187 (19') 59.8-60.0 0.4 1.5060 72 0.8 1.5110 (20') Ref. 16 35 13 13 16, 13 13 0 9, 10 ;> 13 35 i 9 6 a S. M. McElvain and E. L. Engclhardt, THIS JOURNAL, 66, 1077 (1944). C. D. Hurd and L. Schmerling, ibid., 59, 107 M. \ir. Partridge, J. Chew Soc., 3043 (1949). Mi. C. 9. R. Bartz, R. F. Miller and R. ;Idams, ibid., 57, 371 (1935). (1937). Wilson and R. Xdams, THIS JOURSA-., 45, 528 (1928). Q J. v. Braun and W. Schirmacher, Her., 56, 538 (1923). R. T. ilrnold and J. C. McCool, ;bid., 64, 1315 (1942). TABLE I1 PHYSICAL PROPERTIES ASD .~NALYTICAL DATA FOR ARYL ALLYL ETHERS AND SUBSTITUTED 2 allyl ether oc. him. ii25D formula Calcd. Found Substituted phenyl B.p. Empirical Carbon, % p-N(CH3)z 88.1-88.2 0.5 1.5500 CiiHlbNO 74.55 74.89 P-CZHL 96.0-9G. 8 9 1,5124 CiiH140 81.45 81.26 WZ-COOC~H~ 88.0-88.1 0.2 1.5169 C12H1103 69.89 69.80 a-CH3 42 9-43.0 0.8 1.5078 CioH120 81.04 80.70 Substituted 2-allylphenols 4-K(CH3)2 85 0.1 1.5681 CiiH1SNO 74.55 74.67 4-CzHj 63.0-63 5 0.2 1.5301 CilHliO 81.45 81.43 4-CN M.P. 83.0-84.0 5(or ~)-COOCZH~ M.p. 151-152 pressure with a short Vigreux column. The main fraction was refractionated prior to use in the kinetic experiments. The phenols were purified by distillation or recrystallization. nz-Carbethoxyphenol and p-carbethoxyphenol were prepared by esterification of the corresponding liydroxybenzoic acids. p-Ethoxyphenol was prepared from hydroquinone and diethyl sulfate by the method used to prepare anisole from phenol and dimethyl ~u1fate.l~ @-Cyanophenol was prepared from p-aminoplienol by the method used previously to convert p-toluidine to p-tul~onitrile.~~ The rest of the plietiols are available commercially. Allyl p-aniinophenyl ether was prepared by hydrolysis of allyl p-acetaniitioplieiiy-1 ether.lG Allylic chlorides were used for preparing CY- and -,-methylallyl and a,-,-dimethylallyl phenyl ether. These chlorides had the following physical properties: -pmeth>-lallyl chloride, b.p. 83-83.7", %%D 1.4325 (lit.I7 b.p. 83', nZo~ 1.4351); a-methylallyl chloride, b.p. 62.5-63.5', nlj~ 1.4125 (lit.17 b.p. 63.5", 1.4150); a,y-dimethylallyl chloride, b.p. 27" (30 mm.), TZ%D 1.4306 (lit." b.p. 18-20" (12-13 nim.), n% 1.43 11). Commercialll- available 0-methylallyl chloride was used to prepare P-methylallyl phenyl ether. Ethanol was used as the solvent instead of acetone for preparing allyl p-formylphenyl ether.13 Most of the allyl phenyl ethers used in the present work have been described previously. These are given in Table I together with the observed and reported physical properties. CioHsKO 75.39 75.55 CmH14Op 69.89 69.95 That the samules were homoneneous ALLYLPHENOLS Hydrogen, % 8.53 8.24 8.70 8.78 6.84 6.71 8.16 8.10 Calcd. Found 8.53 8.60 8.70 8.58 5.69 5.48 6.84 7.00 was indicated bv the fact that fractionation gave fractions having the -same physical properties. A11 of the samples had the correct chemical composition (carbon-hydrogen analysis) and the infrared spectra showed the samples to be free of phenol. The structures of these several substituted allyl phenyl ethers reported in Table I were confirmed by oxidationi8 to the corresponding aryloxyacetic acids-p-NHz (as its acetyl derivative), p-OC2Hj, p-OCHa, p-CI, p-Br, p-ii02, WL-OCH,~, nz-NO:! and -pCH.,. a,y-Dimethylallyl phenyl ether (presuinably the trans isomer6)), was oxidized to aphenoxyprupionic acid, m.~. 115-116O (lit.19 m.p. 115-116') in good yield. The structures of the p-COsC?H, p-CHO and p-CN phenyl allyl ethers were verified by conversion to p-allyloxybenzoic acid.13 The new allyl phenyl ethers are shown in the upper half of Table 11. The structure of a-methylallyl phenyl ether was established by reduction (palladium-on-charcoal) to sabutyl phenyl ether. The physical properties and infrared spectrum of this product were the same as for an authentic sample.20 The unsaturated ether also was oxidized to aphenoxypropionic acid, m.p. l15-l16°.19 1Vlien heated the ether rearranged to o-crotylphenol (isolated in 947, yield), b.p. 67-68' (0.6 mm.), phenylurethan m.p. 66-67" (lit.21 phenylurethan m.p. 65-66"). The structure of allyl p-ethylphenyl ether was established (14) G. S. Hiers and F. I). Hagcr, "Organic Syntheses," Coll. Vol. I, 2nd edition, John Wiley and Sons, Inc., New York, N. Y., 1941, p. 58. (15) H. T. Clarke and R. R. Read, ibid., 11. 514. (16) L. Claisen, A>tn., 418, 69 (1'31'3). (17) E. H. Huntress and E. E. Toops, Jr., "Organic Chlorine Conpounds," John Wiley and Sons, Inc., Sew York. N. y., 1948. (18) W. M. Lauer and W. F. Filbert, THIS JOURXAL, 68, 1388 (19) C. A. Bischoff, Bey., 33, 925 (1900). (20) M. M. Sprung and E. S. Wallis, Tiirs JOCJRNAI., 56, 1715 (21) I,. Claisen and E. Tietze, Be?., 59, 23-14 (1926). (1936). (1934)

3280 HARLAN L. GOERING AND ROBERT 12. JACOBSOS VOl. so by oxidation to fi-ethylpheiioxyacetic acid, 1ii.p. 96.3- 96.5' (lit.22 m.p. 97"). The structure of m-carbethoxyphenyl allyl ether was established by hydrolysis to nz-allyloxybenzoic acid, m.p. 80.0-80.5'. 23 Anal. Calcd. for CIDHIOO~: C, 67.40; H, 5.66. Found: C, 67.62; H, 5.59. The structure of the latter compound mas established by oxidation to nz-carboxyphenoxyacetic acid, m.p. 207-208" (lit.24 m.p. 206-207"). Allyl p-dimethylaminophen) 1 ether was prepared in 33 % yield by alkylation of the p-amino ether by a method that has been used previously for alkq lating aromatic amines.*j The structure of this compound was established by conver- sion to p-dimethylaminophenol, m,.p. 77.5-78.0" (lit.26 m.p. 78") by refluxing 1 g. of the dimethylamino ether in 7 tnl. of 48'/c hydrobromic acid for 5 hours. The amino phenol nas isolated in 757* yield. Rearrangement of Allyl Phenyl Ethers.-Four of the allyl phenyl ethers listed in Tables I and I1 rearrange to phenols that have not been described in the literature. These new phenols are included in Table 11. The phenols were obtained from the ethers by the procedure given below for the conversion of allyl nt-carbetlioxyphenJ.1 ether to re- arrangement product. This is one of the tno cases where two rearrangement products are possible and the only case F 1 (22) Fig. S. RI. 1.-Dilatometer RlcElvain, "The used in kinetic experinients. Characterization L of Organic Compounds," revised edition, The hlacmillan Co., R-ew York, S. Y., 1953, p. 268. (23) Evidently the melting point of 118O reported for this compound by Scichilone, Gazz. chim. dd., 12, 453 (1882), is incorrect. (24) R. Meyer and C. D. Duxzmal, Ber., 46, 3360 (1913). (26) W, L. Borkowski and E. C. Wagner, J. Oug. Chem., 17, 1128 (1932). (26) H. Wieland, Ber., 43, 712 (1910). in which two products are formed. .i solution of 3.0 g. of allyl m-carbethoxyphenyl ether in 6 g. of diphenyl ether was heated under nitrogen for 9 hours at 220'. After cooling, the solution was extracted with lOy0 sodium hydroxide and the aqueous layer was saturated with carbon dioxide and extracted with ether. Removal of the ether gave a residue, 2.95 g. (98%), which apparently was a mixture of the two possible rearrangement products, i.e., 2-allyl-5-carbethoxyphenol and 2-allyl-3-carbetlioxyphcnol. The higher melting component of the mixture was purified by several recrystallizations. This material is included in Table 11. The lower melting component was not purified. Kinetic Exper;ments.-The dilatometer used to follow the reactions at temperatures of 185 arid 197' is illustrated by Fig. 1. This dilatometer, which was designed for use at high temperatures, differs substantially from thosc used previously for following reactions at much lower teinpcratures (near room temperature).12,27 The important features of this design are: (a) The coiled tube provides a high surface to volume ratio and thus temperature equilibration is rapid. This coil was constructed of 7 mm. thin walled Pyrex tubiug and had a capacity of about 30 nil. (b) The level of the reaction mixture (sealed in the dilatometer at or near room temperature) in the capillary (D) can be adjusted so as to be on scale at the reaction temperature. The capillary (D) was 10 inches long and had a precision bore 0.0224 inch in diameter. The length of the dilatometer from the bottom of the coil to the top of the capillary was about 14 inches. During the kinetic experiments the sealed portion of the apparatus (from A to C) was immersed in the constant temperature bath and held in place by clamps attached to the two glass rods (E and F) which extended through its cover. The constant temperature bath consisted of a Pyrex jar in a well insulated box. The box had a double paned window for observing the scale on the dilatometer. Except when in use the window was covered by a well insulated door. The Pyrex jar (12" in diameter and 18" deep) contained 6 gallons of Dow KO. 550 silicone oil. The bath was heated by two 500 watt heaters. One of t1ie.e served as a constant heater and the other as the intermittent heater. The lattcr was connected in series with a 50-watt light bulb. The constant heater mas connected to a variable viiltage control and the current for this heater was controlled by :L Raytheon line voltage regulator. The temperature of the bath was controlled by a carefully selected Philadelphia type S\Y 912 thermoregulator. The bath was also provided with an eficient stirrer arid a tight-fitting cover. The temperature fluctuations of the bath were less than 0.003" during a rate run and during the period of its use the absolute ternperature varied less than 0.05'. In the kinetic experiments the dilatometer was fillcd as follows. Both A and C were sealed and the reaction mixture n-as added through B at room temperature. After filling to the top of the coil, B was sealed aud a scale with 2 mm. divisions was attached to the capillary tube. For emptying and cleaning the dilatometer A, B and C were opened. The level of tlic liquid in the capillary at the reaction temperature was adjusted as follows. The sealed tiilatomcter was placed in the bath which had previously been heated a few tenths of a degree abovc the operating ternperature. After the excess liquid had overflowed into the reservoir (G) the temperature was lowered to normal and the level of the liquid dropped to the top end of the scale. This operation required about 5 minutes. After equilibration for 10 minutes at the reaction temperature the zero-time reading (Ro) was taken and the rate of decrease in volume was determined. The total drop during a kinetic cxperitnent varied from 50 to 90 mm. and the readings were re- corded to 0.2 mm. The readings were always taken at the same time during the heating cycle (;.e., when the intermittent heater shut off) to minimize error? resulting from the temperature fluctuation of the bath. n'hen the dilatometer was filled with pure solvent the level fluctuated about 0.1 mm. However, when readings were taken at the same time during the heating cycle they agreed to within 0.2 rnm. Thus it appears that the readings in the kinetic csperiments are good to about *0.2 mm. (27) R. Livingston in A. Weissberger's "Technique of Organic Chemistry," Vol VIII, Interscience Publishers, Inc., New York, N. Y. 1953, ChaDt. 2

July 5, 1958 KINETICS OF 0rh.J-CLAISEN REARRANGEMENT 3281 In the kinetic experiments the amount of substrate used was 1.5% by weight of the reaction mixture. This corresponds to a concentration of about 0.1 molar. Theallylaryl ethers were freshly distilled and the solvents were purified as follows. Diphenyl ether was purified according to the method of Kincaid and Tarbell.10 N,N-Dimethylaniline was dried over fused potassium hydroxide prior to distillation and diphenylmethane was purified by fractionation. The other solvents (see Table V) were purified by standard methods. The specific first-order rate constants for the decrease in volume of the reaction mixtures were calculated by use of equation 1 in which Ro, R, and R.CO correspond to the readings at zero time, time t and "infinity" time (;.e., after ten halflives). Since with dilute solutions the change in volume is a k = (lit) In (Ro - I?-)/(& - Rm) (1) linear function of the percentage completion of the reaction,28 k is the first-order rate constant for the reaction. Usually about 25 readings were taken during a kinetic experiment and values of k were calculated for each of these readings. These values did not shov any trends over the range that the reactions were followed (to about 8 1% completion) and the average deviation was usually <2yo of the value of k. In duplicate experiments the values of k agreed within the combined average deviations. A typical kinetic experiment is summarized in Table 111. In this table only every third reading is recorded and thus the average value and average deviation may differ slightly from the value recorded in Table IV. TABLE I11 RATE OF REARRANGEMENT OF ALLYL +CRESYL ETHER IN DIPHENYL ETHER AT 184.85'" Time, 10-8 sec. Dilatometer reading k X 106 set.-* 0 67.2 . 2.70 65.2 2.05 5.40 63.3 2.05 8.00 61 .O 2.05 14.4 57.8 2.05 19.8 54.9 2.06 25.2 52.3 2.07 30.6 49.9 2.08 36 0 47.8 2.09 57.6 41.6 2.09 72.0 38.8 2.08 03 30.6 . Average 2.07 f 0.02 a The reaction mixture consisted of 1.5% by weight of the substrate in diphenyl ether. First-order rate constants fo- the rearrangement of all but two of the ethers listed in Tables I and I1 were determined by this method. Allyl m-nitrophenyl ether decomposes in diphenyl ether at th reaction temperature and thus the rate of rearrangement of this compound could not be determined. For some unknown reason a,?-dimethylallyl phenyl ether showed erratic behavior and the rate of decrease in volume of the reaction mixture was not reproducible. Results The results of the kinetic experiments are presented in Tables IV and V. In these experiments the concentration of substrate was 1.5% by weight of the reaction mixture (approximately 0.1 M). First-order rate constants for the rearrangement of nineteen ethers in diphenyl ether at 184.85 and 19'7.29" are given in Table IV together with the Arrhenius activation energies, Ea, and entropies of activation, AS*. Similar data for the rearrangement of allyl 9-cresyl ether in benzonitrile are in- (28) J. A. Riddick and E. A. Troops In A. Weissherger's "Technique of Organic Chemistry," Vol. VII, Interscience Publishers, Inc., New York, N. Y. 1956. TABLE IV RATE CONSTANTS AND ACTIVATION PARAMETERS FOR THE REARRANGEMENT OF SUBSTITUTED ALLYL PHENYL ETHERS IN DIPHENYL ETHER "JLICUFUL aromatic rinr or suL':',.-' in ~.~. Ea, AS*,a allyl k X 106, set,-; k X 106, set,-; kcal / ral / portion 184.65 f 0.05 197.29 i 0.02 ~. mole degree p-N(CHs)i 14.3 f 0.2 38.7 f 0.5 34.3 - 2 P-NHa 10.0 f .2 27.4 f .2 34.7 - 2 fi-OCzH6 4.77 f .04 12.5 i .1 33.1 - 7 p-OCHa 4.58 f .Olb 12.2 f ,1 33.6 - 6 P-CHI 2.08 f .Ole 5.58 f .05 34.0 - 7 fi-CzH6 2.00 f .03 5.51 f .04 34.8 - 5 9-Cl 1.70 f .02 4.21 i .04 31.2 -13 p-Br 1.58 f .03 3.92 f .02 31.2 -13 None 1.52 f .0Zb 3.86 f .03 31.6 -12 fip-COOCzHa 1.115 + ,005' 2.80 f .04 31.5 -13 9-CHO 1.07 f .01 2.72 f .03 32.2 -12 9-COCHs 0.994 f .007 2.54 f .03 32.2 -12 p-CN 0.903 + ,007 2.285 zt .005b 32.0 -13 $-NO1 0,892 f .004' 2.26 f .02 31.9 -13 m-OCHs 4.92 f .05 11.9 f .02 30.4 -13 n-COOC1Hs 1.48 f .02 3.51 f .04 29.8 -16 a-CHa 21.1 f .2 52.5 f .7 31.4 - 8 @-CHI 1.32 f .02 3.29 + .03 31.5 -13 r-CHa 1.61 f .02 4.05 f .04 31.7 -12 #-CHE 2.49 f .03d 6.60 f .OSd 34.6d - jd Calculated for T = 184.85'. Average value (and average deviation) of two independent kinetic experiments. Average value (and average deviation) of four independent kinetic experiments. Reference 5 reports k = 2.69 X 10-6 sec.-l at 185.8', E. = 33.1 (14.2% solution). These data are for the rearrangement of the p-methyl ether in benzonitrile. cluded in this table. Several of the constants in this table are average values (and average deviations) of more than one independent kinetic experiment. As indicated by the magnitudes of these deviations the rate constants are generally reproducible to within 1%. The rest of the constants are average values (and average deviations) of about twenty-five values determined during the course of the reaction. Judging from the reproducility of the rate constants the activation energies are probably reliable to within 1 kcal. The entropies of activation (calculated from the frequency factor, TABLE V RATE CONSTANTS FOR THE REARRAN'GEMENT OF ALLYL 9-CRESYL ETHER IN SEVERAL SOLVENTS AND ALLYL pCARBETHOXYPHENYL ETHER IN ETHYLENE GLYCOL AT 184.85 O A. Allyl p-cresyl ether Solvent k X 106, sec.-l Ethylene glycol 18 i 1" Benzyl alcohol 9.7 f 1.0 1-Octanol 9 f2 Phenol 45 & lb Carbitol 3.6 f 0.3 Methyl salicylate 2.45 f .O1 Benzonitrile 2.49 f .03 N,N-Dimethylaniline 2.46 f .04 Acetophenone 2.41 f .12 Diphenyl ether 2.08 f .Ole Diphenylmethane 2.12 f .02 Decalin 1.56 f .O1 B. Allyl P-carbethoxyphenyl ether a Average of four independent determinations. Ethylene glycol 6.4 f 0.6 * Average of two independe it determinations

328% HARLAN L.GOERINC AND I~OBEKT I<. JACOBSON Vol. 80 Aj are probably good to within 2 or ti entropy units. Coinparison of the rate constants in Table IV for the series of fi-substituted allyl phenyl ethers shows that the rate of rearrangement is increased by electron-supplying substituents and decreased by electroti-ivithdrawing substituents. However, the reaction is rather insensitive to these structural changes and at 1%" there is only a sixteenfold variation within the series. Lloreover, the activation energies are higher with electron-supplying substituents than with electron-withdrawing substituents and thus the spread iii the rate constants decreases with temperature. For example, the extrapolated rate constants for the most and least reactil-e members of the series differ by only a factor of 3 at 30". The data presented ill Table IV also show the effects of methyl substituents in the allyl part of the ether. -1s in the case of the finra-Claisen rearrangenient29 substitution of a y-hydrogen atom by a methyl group has essentially iio effect on the rate or activation energy of the rearrangement. Siniilarly the effect of a j3-methyl substituent is siiiall as might be expected. On the other hand, ;is has been predicted,'g an a-methyl substituent has a relatively large effect and increases the rate by a factor of 14. The thermodynarnic data are not accurate enough to tell whether this increase in rate is due to an increase in entropy of activation or decrease in activation energy. Rate constants for the rearrangement of allyl pcresyl ether in several solvents and allyl p-carbethoxypheiiyl ether in ethylene glycol at 1S4.83" are given in Table V. X11 of the noti-hydroxylic solvents except acetophenolie were stablc at the reaction teaperature, i.e., when the pure solvents were heated in the dilatometer no \wluiiie changes wcre observed. Furtherinore the rearrangement product was stable in these solvents and no changes in volume were observed after the reactions were complete. On the other hand, acetophenone and the hydroxylic solvents except phenol and methyl salicylate showed n slow clccrease in voluiiie when heated at the reaction temperature. lloreovcr, in the hydroxylic solvents the rearrangeinent product apparently undergoes a change subsequent to its formation which results in a slow voluirie coiitractioii. b-heii a pure sample of the rearrangement product, a ~-allyl-~4-1i1etli~l~,henol, was heated iii ethylene glycol the \-oluiiie contractcd at :L soiiiewhat greater rate than wheii the pure solvent was heated. Similarly, when the re:irrangenient product was heated in phenol the volunic contracted slowly, whereas with the pure solvent iio coiitraction was observed. This may be due to the conversion of the rcarratigenierit product to dihydrobenzofuran. The rate of the contraction resulting from these side reactions was much slower than that due to the Claisen rearrangement. In these experiments the infinity readings (at ten half-lives) were corrected -the niagnitucle of the rather small correction was estimated froni the rate of contraction of a solutioii of the rcarrangeineiit product- and the rate constants were computed in the usual tiiatiner. The constants obtained in this way were (1935). (20) S. J. Rhuads and R. I,. Crrcclius, Tins JDURNAI. 77, 3027 within the conibinecl average deviations of the constants determined by the Guggenheirn30 method. Because of these complications the rate constants for the hydroxylic solvents and acetophenone are not as reliable as those for the non-hydroxylic solvents. For this reason activation energies for the rearrangement in hydroxylic solvents were not determined. -1s illustrated in Table V rate constants for duplicate experiments in ethylene glycol and phenol showed average deviation of about 3 and 2%, respectively. Glycerol, nitrobenzene and caproic acid contracted too rapidly at the reaction temperatures to be used in the kinetic experiments. The data presented in Table V show that the rate of rearrangement is remarkably insensitive to variation of the iiiediuni. Rate constants for the rearrangement in the six non-hydroxylic solvents arid methyl salicylate differ by less than a factor of 2, and 4 of the constants are essentially the smie. The reaction is soinewhat faster in hydroxylic solvents. The 1s-fold difference in the rate in phenol and methyl salicylate suggests that the greater rate in the hydroxylic solvents may in some way be connected with hydrogen bonding between the solvent and substrate. The greater rate in phenol than in nun-hydroxylic solvents is consistent with the observationio that the apparent first-order rate constarit for the rearrangement of allyl p-cresyl ether in the absence of solvent increases as the iiiediuni changes from allyl p-cresyl ether to 2-allyl-4- inethylphenol. -1ltliough the solvents were only compared at one temperature it appears that the relative rates 1% ould not change appreciably with temperature. The last entry in Table IV shows that the activation energy lor the reaction in benzonitrile is within experimental error of that for the rearrangeiiierit in diphenyl ether. Comparison of the relatiw rates of rearrangement of the 11- methyl arid p-carbethoxy substituted ethers in ethylene glycol (Table IT) and diphenyl ether (Table IT) shows that the reaction is more sensitive to \-ariation of the substituent in the former solvent. Discussion It is apparent from the relative reactivities of the p-substituted allyl phenyl ethers (Table IV) that there is a qualitative relationship between reactivity and the substituent constants, u, i.e., reactivity decreases as u increases. It was of interest to cleterniine whether these rate data could be correlated quantitatively by the substituent constants. -1 complicating factor in treating the data is that there are two reaction sites. One of these is I)UY(L to the substituents (carbon-oxygen bond cleavage) and the other is lneta to the substituents (carboncarbon bond formation). It appeared that the nature of the correlation might provide information concerning the relative effects of the substituents at the two reaction sites. For example, if the substituents have a inuch greater effect on bond breaking than bond making, a linear relationship between the reactivities and the up constants might be expected. On the other hand, if the substituents have an effect on both bond making and bond breaking one might expect a correlation between (30) bee reftrenci 12a

July 5, 1958 KINETICS OF O~~~O-CLAISEN REARRANGEMENT 3283 the rates and a linear combination of the up and urn constants. Because of these complications the data were treated in several ways. The substituent constants used in the various correlations are shown in Table VI. TABLE VI SUBSTITUEST CONSTANTS USED FOR CORRELATING REACTIVITIES OF p-SUBSTITUTED ~LLYL PHENYL ETHERS $-Substituent upa Urn uD +b brn +c N(CH3)z -0.600 -0,211 -1.67 -0.211 "2 - ,660 - ,161 -1.33 - ,161 OCzHj - ,250 ,150 -0.76d . 047d OCHB - ,268 ,115 - .76 ,047 CH, - ,170 - ,069 - .31 - ,069 CzHj - ,151 - ,043 - .29 - ,063 c1 .227 ,373 .ll ,373 Br .232 ,391 .15 ,391 None 000 . 000 .oo 000 COOCzHj ,522 ,398 . . . . . COCHJ ,516 ,306 . . . . . CN ,628 ,678 . . . . . NO2 ,778 ,710 . . . . . These values were taken from ref. 32. These values were taken from ref. 33a except the values for P-iS(CH3)z and p-NHz which were taken from ref. 33b. The a+ values for electron-withdrawing substituents are similar to the u values. Since up+ values were not available for all of these substituents, uD values were used. These values were taken from ref. 33a except for the values for NH2 and h-(CH3)* for which u values were used because u+ values were not available. Since urn + values were not available for all of the electron-withdrawing substituents urn values were used. This value was assumed to be the same as that for The data are not correlated well by the Hammett relation~hip,~~J~ (eq. 2) if up substituent constants are used. As illustrated by the upper plot in Fig. 2 the relationship between log k/ko and the Hammett up values is not linear. For those p-substituents which have two u values, depending on the nature of the reaction, up values rather than up* values32 were used in this plot. It is apparent that the up* values would show larger deviations than the up values. In this treatment the effect of the substituents at the m-position (where the allyl group becomes attached to the aromatic ring) has been neglected. A substantially poorer correlation (not shown) is obtained using urn constants instead of up constants. As illustrated by the lower plot in Fig. 2 the data are correlated very well by the Hammett relationship (eq. 2) using Brown's up+ values.33 The equation for the least-squares fit is log k/ko = -0.510up+ + 0.078 The standard deviation from the least-square line (s) is 0.064 and the correlation coefficient (r) is 0.988.34 Rate data for allyl fi-formylphenyl ether have not been included in this or the other plots OCHa. log k/k" = pa, (2) (3) (31) L. P. Hammett "Physical Organic Chemistry," McGraw-Hill (32) H. H. Jaffk. Chem. Ret's., SS, 1U1 (1953). (33) (a) H. C. Brown and Y. Okamoto, THIS JOURNAL, 79, 1913 (1957); J. Org. Chem., 22, 485 (1957); (b) N. C. Deno and W. L. Evans, THIS JOURNAL, 79, 5801 (1957). (34) These quantities were calculated by the methods described in reference 32. Book Co., Inc., iYew York, N. IT., 1910, Chapt. VII. , - 08 -9.4 07, Oi4 0,.8 , 0 ruCvNLi CI - H Noi - 0.21 COM~-8 J 0, 3 0.2 - 0.2 q+ Fig 2.-Plots of log k/kO verszis a,> and a,+ because the up+ constant has not been reported and it seems evident that the up value (based on one reaction32) is much too low. The up+ constant for pformyl calculated from the rate data in Table IV by use of equation 3 is 0.4G3. The data for the two m-substituted allyl phenyl ethers included in Table IV show positive deviations from this plot and have not been included. The deviation is especially serious for the m-methoxy ether. In this case the observed rate is about three times greater than that calculated from the urn+ value.ciG The failure of the correlation for the nz-substituted ethers apparently is not due to the fact that the substituent is ortho to one of the two possible positions to which the allyl group can migrate. The m-methoxy ether, which shows the largest deviation, is reported to give only the product resulting from rearrangement of the allyl group to the position @ara to the substituent,35 ;.e., 2-allyl-3- methoxyphenol. Thus it appears that in this case the position ortho to the substituent is not involved in the reaction. As shown in Table VI there is little difference between the um and urn+ values. As indicated above, the correlation is very poor using values and it is thus apparent that am+ would also give a poor correlation. Jaff6 has suggested32 that in cases (such as the present) where the substituents are both meta and (35) F. Mauthner, J giakl Cheni , 102, 41 (1921)

3% 4 HARLAN L. GOERIKG AND KOBERT R. JACOBSON VOl. so I I I I I 0.6: d 5 0 ff 0.2- -0.2- -0.2 -1.4 -1.0 - q+-o .7 5 G : Fig. 3.-Plots of log k/kO Z'FYSUS (ul, - a,) and (u,+ - 0.75,", &). that obtained with the up values and is considerably poorer than that obtained with the up+ constants. The least-squares equation for this plot is The standard deviation is 0.1 S and 7' = O.S!1S. log k/ku = - 1 ,>I(U,> C - um) - O,(J54 (3fi) This ecliiation recently h:~. heen applied tn the iw!lrn-Claisen rearranxement of p-substituted allyl phenyl ethers by 11. S White. P! 01, Abstracts uf the 131'nd Rleeting of the American Chemical Suciety, September. 19.57. Xew York, N. Y., 1). CiCi P. See also W. S. \Vhite. D. Gwynn, R. Schhtt, C. Gerard and 1%'. Fife, THIS JOURNAL 80, 3iil (195X). The data also were treated by equation 4 using u+ constants instead of u constants. In this case pm:pr, = -0.i5 and thus log klko was plotted against (up+ - 0.T5nmt). As illustrated by the lower plot in Fig. 3 this relationship is indeed linear. This correlation is slightly better than that obtained using up+ constant; s = 0.046 and r = 0.994. The least-squares equation is log k/ku = -0.678(upC -0.75 urn') -0.049 In the latter correlation pp = -0.6'78 and pm = O.,jOS. This implies that the reaction is facilitated by electron supply to the P-position (the ether linkage) and electron removal from the m-position. However, this is clearly an illusion. This is shown by the fdct that the data are correlated by both equation 2 and equation 4 if ut constants are used. These two linear relationships are shown by equations 3 and 6. log klko = pur,L log klkU = ~p[~p+ + (~m/~iJ~m+l Since these two equations hold, the relationship shown by equation 7 must also hold for the substituents used in the present work. UI,+ = P'(U,+ + Cum+) In the latter equation p' and C are pp lp (equations 3 and 6) and pml'pp (equation G), respectively. Conversely, if the linear relationship shown by equation T holds it becomes apparent that any reaction series that can be correlated by the Hammett equation will also be correlated by the four parameter equation. Thus the significance of the two paratneters designated as pp and pm in the four paratneter equation (I and 6) is obscure. The relationship shown by equation 7 was tested using both u+ and u constants. a'ith each type of constant the relationship was found to be linear. =\ plot of up+ versus up+ - O.T5am+ (C = -0.75) using constants for 23 substituents was linear, ,of = 1.28, Y = 0.9i2, s = 0.15. .I plot of up aersus up - u, (C = - 1) using the values given in Table VI was also linear, pf = 1.i5, r = 0.930, s = 0.16. This clearly shows that equation T holds and consequently it appears that equation 4 cannot be used for its intended purpose. The theoretical significance of the correlation of the rate data by the u+ constants is not obvious. Perhaps the most important observation in this connection is that the data for the p-substituted ethers are correlated by up+ rather than urn+. The reaction is electron demanding, i.e., p is negative, and presumably the substituent effect is transmitted primarily through the 9- carbon-oxygen bond. The dependence of the rate on upc rather than um + implies that the transition state resembles the reactant more closely than the product. It is not clear why in the present case the data are Correlated by u+ constants instead of u constants. There are a nu~ber of other reactions which are correlated better by UT than by u constants.33 However, for the most part these are cases where p is large and negative, i.e., the reaction is sensitive to substituent effects. The present reaction is relatively insensitive to substituent effects. The rather small effect of substituents is not sur- ( 3 (6) ( 7)

July 5, 1958 CYCLIZATIONS OF 2-DEUTERIO-2’-CARBOXYBIPHENYLS 3-385 prising. If the reaction is considered to involve simultaneous homolytic electron displacements p would be expected to be small. If simultaneous heterolytic displacements were involved the substituent effects at the m- and +positions would be large but opposite in sign. Because of this cancellation the over-all effect would be small. 37 The present data do not rule out the possibility (37) Ambiguities concerning the nature, i.e., homolytic or heterolytic, and direction of electron displacements in concerted cyclic processes have been discussed by C. K. Ingold. “Structure and Mechanism in Organic Chemistry.” Cornell University Press, Ithaca, N. Y., 1853, pp. 597, 637 and 641. that an intermediate may be involved in the rearrangement.38 However, there do not seem to be any reasons for suspecting that this is the case. It appears that the data are consistent with a concerted one-step cyclic mechanism. The geometry of the transition state for such a mechanism has been discussed previo~sly.~~~~ (38) If an intermediate is imolved the apparent first-order rate constant is a composite of three rate constants. The substituent and solvent effects can be predicted for the individual steps but not for the composite. MADISON 6, WISCONSIN [CONTRIBUTION FROM THE SCHOOL OF CHEMISTRY, RUTGERS, THE STATE UNIVERSITY ] Deuterium Isotope Effects in Some Acid-catalyzed Cyclizations of 2-Deuterio-2 ’-carboxybiphenyl BY DONALD B. DENNEY AND PETER P. KLEMCHUK’ RECEIVED DECEMBER 23, 1957 2-Deuterio-2’-carboxybiphenyl has been cyclized to fluorenone with sulfuric acid, polyphosphoric acid and anhydrous hyHydrogen fluoride cyclization exhibited a The significance of drogen fluoride. kH/kD of 3.02, whereas the other acid-catalyzed cyclizations had isotope effects in the range 1.13-1.46. these results is discussed with respect to possible mechanisms for these substitutions. The isotope effects for these reactions have been determined. Melander’s2 pioneering studies on hydrogen isotope effects in aromatic nitration and bromination are now classics. Since his work was published many papers have appeared in which deuterium and tritium isotope effects have been measured during aromatic substitutions. These studies have led in general to a greater understanding of the mechanisms of these reactions and have specifically provided information concerning intermediates in the reaction sequence as well as to whether or not loss of hydrogen is involved in the rate-determining step. We wish to report at this time some measurements of deuterium isotope effects obtained during the acid-catalyzed cyclization of 2-deuterio-2‘- carboxybiphenyl (I) to 4-deuteriofluorenone (Va) and fluorenone (Vb). As it can be seen, the isotope effects being measured here are those which have been termed intram~lecular.~ This system D 040 \ HI I COOH D 0 Vb (1) Alfred P. Sloan Fellow in Chemistry, 1956-1957. (2) L. Melander, Arkiv Kemi, 2, 213 (1950). (3) (a) W. hl. Lauer and W. E Noland, THIS JOURNAL, 75, 3689 (1953); (b) T. G. Bonner. F. Bowyer and G. Williams, J. Chem. Soc., 2650 (1953); (c) P. B. D. de la Mare, T. M. Dunn and J T. Harvey, ibid., 923 (1957); (d) H. Zollinger, Helu. Chim. Acta, 88, 1597 (1955); (e) U. Berglund-Larsson and L. Melander, Arkiv. Kemi, 6, 21 (1953); (f) T. G. Bonner and J. M. Wilkins, J. Chem. SOL., 2358 (1955); (g) E. Grovenstein, Jr., and D. C. Kilby, THIS JOURNAL, 79, 2972 (1957). (4) K. B. Wiberg, Chem. Rens. 66, 713 (1955). was chosen because it provides a degree of flexibility not easily obtained when intermolecular isotope effects are measured. For example, it has been possible to measure isotope effects of very fast reactions by this technique, since the isotope effect is obtained simply by analyzing the mixture of Va and Vb for deuterium. We also have been able to measure isotope effects in heterogeneous reactions such as the Friedel-Crafts reaction by the use of this techniq~e.~ The isotope effects which we have observed can be found in Table I. It is apparent TABLE I Time, Teomp., Catalyst min. C. kdkn Concd. sulfuric acid 2-60 1 1.31+0.03 86. FAY0 sulfuric acid 90 1 1.13+ .02 Polyphosphoric acid 24 hr. 26 1.16 f ,01 96.63y0 sulfuric acid 15 1 ‘1.31f .03 Polyphosphoric acid 15 95 1.31 i .03 Hydrogen fluoride 30 19 3.02 f .11 that all of the reactions studied exhibit some isotope effect. The range is considerable from a kH/kD of 3.02 in anhydrous hydrogen fluoride to 1.13 in 86.54% sulfuric acid. In order to accept these values as being meaningful, it was necessary to prove that exchange was not taking place during the reaction. This sort of analysis has been accomplished for the sulfuric acid-catalyzed reaction. At various time intervals aliquots of the reaction mixture were removed and the fluorenone was isolated and analyzed for deuterium. All of the samples of fluorenone had the same deuterium content. If exchange was taking place with either the starting acid or the product, fluorenone, then there would be a steady decrease in the deuterium content of the fluorenone. Since this was not observed one knows that the isotope effects ob- (5) Unpublished work