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Cyclobutane-bicyclobutane system—I
CYCLOBUTANEBICYCLOBUTANB
SYSFEM-I
THE BEIATIVE REAmrrY OF THE CENTBAL BONDIN BICYCLI)%UT'ANECARBONRBOPICIRHeANDlHEDOUBLEBOND INCRUTONDNIlRILEMNUCLEOPHILICREACIlONS
S. HOI and D. AuRBACH
HH2 RESULTS AND DISCUSSION
The reactions of the two substrates with MeO/MeOH and i-PrO /i-PrOH were carried out at 30.5 and 50S and followed by GC analysis. Substrate concentration ranged from 0.02 to 0.08 M of I and 0.05 to 0.1 M of 2. Alkoxide concentrations were 0.02-0.7 M. The reactions were first order in the concentrations of both the substrate and the catalytic alkoxide (correlation coefficients were better than 0.996). The reactions are essentially irreversible and go to completion. Reaction rate constants and activation parameters are given in the table. Addition of crown ether to the reaction mixture in i-PrOH, induced an increase of more than an order of magnitude in the reactions rates at 30.5°. At 50S in the presence of crown ether. the reactions were too fast to be measured. The literature value for the reaction of 2 with i-PrO-IiPrOH is 0.05 M-' min" at 24°.~ Extrapolation of data from the table to this temperature yields a value of 0.04 M" min' I which is in good agreement with the literature value. As expected from its higher ground state energy," the trans isomer is more reactive in MeO-/MeOH than the cis. In i-PrO-/i-PrOH isomerization is much faster than addition. therefore the rate constant in the table represents the rate of disappearance of an equilibrium mixture of the two isomers (ca. 2: 3).Taking into account a statistical correction factor of 2 as the double bond can undergo nucleophilic attack on both faces while nucleophile approach to 1 is limited to one direction only. one finds that the relative reactivity of 1 and 2 ranges from I : I to I: 5 depending upon the nucleophile and the reaction conditions. The lower reactivity of 1 with MeO-/MeOH as compared to that of 2 results from a lower entropy of activation, since its enthalpy of activation is equal to that of the trans and even lower than that of the cis isomer of 2. In contrast to reactions in MeOH. the difference in reactivity in i-PrOH stems from a lower enthalpy of activation for 2 while the activation entropy is greatly in favour of 1. These results show that bicyclobutane has about the same reactivity toward nucleophiles as that of the double bond. The retardingeffect of alkyl substituents on the rate of nucleophilic reactions results from both their steric and electroniceffects.' An examination of models shows that a nucleophile's approach to 1 is more sterically hindered than its approach to 2. which means that the net reactivity (after deduction of steric factors) of the central bond in I is greater than that of the double bond in 2. Experimental support for the relative steric effects present in I and 2, was obtained from reactions with i-PrO-/i-PrOH in the presence of 18-erown-6-ether. This probe is generally used to characterize the more sterically hindered protons participating in HX elimination
reactions." The removal of the sodium cation from the ion pair nucleophile-metal reduces its size. leading. in general. to an increase in the reaction rate. Clearly. the more sterically hindered substrate will benefit more from this reduction in the size of the reagent. An examination of the data in the table reveals that the relative rate of i-PrO' addition to 2 and 1 at 30.5° changes from 3.4 to 2.7 as crown ether is added to the reaction mixture supporting the previous conclusion based on the models that nucleophilic approach to I is more hindered than in 2. On the reasonable assumption that the electronic rate retardation caused by the two methylenes in I is at least equal to that of the single Me group in 2. one concludes that the intrinsic reactivity of the central bond in I is greater than that of the analogous double bond. C-C single bonds do not usually cleave as a result of a nucleophilic attack on one of the C atoms. The nucleophilic cleavage of a cyclopropyl ring usually necessitates the presence of two activating groups such as nitrile." Mono-activated cyclopropanes can be cleaved only if subjected to powerful nucleophiles under drastic conditions.9 b •c A single cyano group is sufficient to make such a process feasible in an unsaturated system. Thus. the general reactivity scale for this type of reaction including the bicyclobutanic bond is: C-C (normal
General. For analytical purposes. a Packard Model 878 (Flame ionization detector) gas-chromatograph was used. whereas for preparative purifications of starting materials and products a Varian 920 gas-chromatograph (Thermal conductivity detector)
Table I. Second order rate constant for the reaction of I and 2 with MeO'/MeOH and i-PrO'/i-PrOH. Solventl Nucleophile I 2 trans 2 cis I 2 It 2t
MeOH/MeO' MeOH/MeO' MeOH/MeO' i-PrOH/i-PrO' i-PrOH/i-PrO' i-PrOH/i-PrO' i-PrOH/i-PrO'
klO~'/M"
min"
0.00356 0.0332 0.0256 0.0186 0.063 0.32 0.86
k'o"/M" min" 0.0269 0.248 0.203 0.108 0.243
tEquivalent amount of Ill-crown-6-ether was added to reaction mixture.
.lW kcal/mol 18.8 18.8 19.3 15.3 12.4
~S'
e.u.
- 15.9 - 11.5 -10.1 - 24.3 - 31.2
crJoaclerse_bicrcbaaarw
8ll3
wa8pr8pd8ddxd8ttbcl88ctiateapwitbtbe8p pmprb&mobdthe 8kubddoxNawbhSmpkadca
%.B.&li!
GLNAT
R. P. Ci D. S. Coma. P. 21.2749flssn: ‘J. K: Hdl. E. P. Bkcbmd. B. iZ.Cbakofmky.J: B. Bi$ uii W. A. Scppud, 1. Am. Ckm Ser. 93. II0 (1971):‘E. P. Bhmhnl. Jr.udA.~BI+I,ltT(l~:‘M.~R.N. Wik G. w. Glnbmmd IJ. Roy,Jbidw 2752wm,. ‘It. W. Cox. N. D. Humomy.G. Ndm madK. B. Wiberg.1. csem.F&y&66. IN mm. ‘II. D. Newtonmd J. M. Bchdmm.1. Am. Chm. Sk 94.767 (1972). sMmdzR#wopat7kckllI~of#ukeJe&p.461. Wiky. New YaL (l%5). ‘R. N. R& G. C. Tcsoroml D. R. Moore.J. Gvg.C&m. 32 1.91(I%7). t. K. I&d ud W. 1. Powll. 1. clnr. Ser. 119.I976 (1921). ‘J. W. Cmmp.1. arc. Chm. 21.933 (1%3). a A. Butch. Ace. Oar Ra. 6, m (1973):E. Bsioccbi R. Rtudwei~sc~I.cLIIII.soc.PefkinII.436(I977). “SDhkfakymdR.K.~I.AmCkt.Sor.97.3239 (1975):‘A. B. !Mb md R. M. !hbom@. Jr.. Tetmhdma L&UI l6@ (19n): ‘W. E. Tmce ud L B. Liody. 1. N. cmm. y 1463(l%l). ~.HmaIsdS.HPail.I.ArrCYwrr.S#.%,6122(19n). “K. B. Wibem K. s. Pekrs, G. B. EBiumud F. ARmi. /bid
. -
purhlbythemmmivik
mllre.“baepuhaiatochmdr/wimomwstadtbdr . . . dclltBaboaiarbo~“Tbcc&lad_irawnd skopmpox~ebkmaaubaihJc-by~ rcmioatimcs~ytothcOk NNRrpechrradGC . . damtms Pa tma~Sixyc~ NMR CCDCIJ) b: b I.13 (6 6H). 24s (a&4HA 2% (111, IH), 3.3(m IH) uul 4.3 (q. IH). (portad:C. 66% H, 9.27; N. 10.20.Cdc. C. 69m H. 9.33;N. lO.U7%).Fa the clr kmcr NMR (CDC&)6 1.1s (d. 6H). 21-26 (a, JH). 3.3 (a. IH) rad 3.9 (a. IH). ;Fg; C. 6&92;H. 9.53;N. 10.24.Clk. C. 69.06;H. 9.35;N. Kiwic~Baocksohsoftbe~~ in&mdstmdwd@ip&aylforreacahswitbIradubolwRb2)
99.3946ml. “CkmkdRemMtyadRcatkmPathsfEdaadbyG.Kbpau). Wiky-htemdmm. New Yak 11971):R. F. Hmdsor~. A&w.&uIsrEd.li36(I973). .. ‘O.W.OoLcLc.~Liom.~.P.HvrbrsdF.~.~oolr.I.~a. cam. 1). 2445 w74~. ‘9. ikllyba Buff.s#. ckm. Be& 31.223 wz2). “N. tivseh.N.Sc.Tbeak,Bar-lhnUivenity (1978).
SYSFEM-I
THE BEIATIVE REAmrrY OF THE CENTBAL BONDIN BICYCLI)%UT'ANECARBONRBOPICIRHeANDlHEDOUBLEBOND INCRUTONDNIlRILEMNUCLEOPHILICREACIlONS
S. HOI and D. AuRBACH
HH2 RESULTS AND DISCUSSION
The reactions of the two substrates with MeO/MeOH and i-PrO /i-PrOH were carried out at 30.5 and 50S and followed by GC analysis. Substrate concentration ranged from 0.02 to 0.08 M of I and 0.05 to 0.1 M of 2. Alkoxide concentrations were 0.02-0.7 M. The reactions were first order in the concentrations of both the substrate and the catalytic alkoxide (correlation coefficients were better than 0.996). The reactions are essentially irreversible and go to completion. Reaction rate constants and activation parameters are given in the table. Addition of crown ether to the reaction mixture in i-PrOH, induced an increase of more than an order of magnitude in the reactions rates at 30.5°. At 50S in the presence of crown ether. the reactions were too fast to be measured. The literature value for the reaction of 2 with i-PrO-IiPrOH is 0.05 M-' min" at 24°.~ Extrapolation of data from the table to this temperature yields a value of 0.04 M" min' I which is in good agreement with the literature value. As expected from its higher ground state energy," the trans isomer is more reactive in MeO-/MeOH than the cis. In i-PrO-/i-PrOH isomerization is much faster than addition. therefore the rate constant in the table represents the rate of disappearance of an equilibrium mixture of the two isomers (ca. 2: 3).Taking into account a statistical correction factor of 2 as the double bond can undergo nucleophilic attack on both faces while nucleophile approach to 1 is limited to one direction only. one finds that the relative reactivity of 1 and 2 ranges from I : I to I: 5 depending upon the nucleophile and the reaction conditions. The lower reactivity of 1 with MeO-/MeOH as compared to that of 2 results from a lower entropy of activation, since its enthalpy of activation is equal to that of the trans and even lower than that of the cis isomer of 2. In contrast to reactions in MeOH. the difference in reactivity in i-PrOH stems from a lower enthalpy of activation for 2 while the activation entropy is greatly in favour of 1. These results show that bicyclobutane has about the same reactivity toward nucleophiles as that of the double bond. The retardingeffect of alkyl substituents on the rate of nucleophilic reactions results from both their steric and electroniceffects.' An examination of models shows that a nucleophile's approach to 1 is more sterically hindered than its approach to 2. which means that the net reactivity (after deduction of steric factors) of the central bond in I is greater than that of the double bond in 2. Experimental support for the relative steric effects present in I and 2, was obtained from reactions with i-PrO-/i-PrOH in the presence of 18-erown-6-ether. This probe is generally used to characterize the more sterically hindered protons participating in HX elimination
reactions." The removal of the sodium cation from the ion pair nucleophile-metal reduces its size. leading. in general. to an increase in the reaction rate. Clearly. the more sterically hindered substrate will benefit more from this reduction in the size of the reagent. An examination of the data in the table reveals that the relative rate of i-PrO' addition to 2 and 1 at 30.5° changes from 3.4 to 2.7 as crown ether is added to the reaction mixture supporting the previous conclusion based on the models that nucleophilic approach to I is more hindered than in 2. On the reasonable assumption that the electronic rate retardation caused by the two methylenes in I is at least equal to that of the single Me group in 2. one concludes that the intrinsic reactivity of the central bond in I is greater than that of the analogous double bond. C-C single bonds do not usually cleave as a result of a nucleophilic attack on one of the C atoms. The nucleophilic cleavage of a cyclopropyl ring usually necessitates the presence of two activating groups such as nitrile." Mono-activated cyclopropanes can be cleaved only if subjected to powerful nucleophiles under drastic conditions.9 b •c A single cyano group is sufficient to make such a process feasible in an unsaturated system. Thus. the general reactivity scale for this type of reaction including the bicyclobutanic bond is: C-C (normal
General. For analytical purposes. a Packard Model 878 (Flame ionization detector) gas-chromatograph was used. whereas for preparative purifications of starting materials and products a Varian 920 gas-chromatograph (Thermal conductivity detector)
Table I. Second order rate constant for the reaction of I and 2 with MeO'/MeOH and i-PrO'/i-PrOH. Solventl Nucleophile I 2 trans 2 cis I 2 It 2t
MeOH/MeO' MeOH/MeO' MeOH/MeO' i-PrOH/i-PrO' i-PrOH/i-PrO' i-PrOH/i-PrO' i-PrOH/i-PrO'
klO~'/M"
min"
0.00356 0.0332 0.0256 0.0186 0.063 0.32 0.86
k'o"/M" min" 0.0269 0.248 0.203 0.108 0.243
tEquivalent amount of Ill-crown-6-ether was added to reaction mixture.
.lW kcal/mol 18.8 18.8 19.3 15.3 12.4
~S'
e.u.
- 15.9 - 11.5 -10.1 - 24.3 - 31.2
crJoaclerse_bicrcbaaarw
8ll3
wa8pr8pd8ddxd8ttbcl88ctiateapwitbtbe8p pmprb&mobdthe 8kubddoxNawbhSmpkadca
%.B.&li!
GLNAT
R. P. Ci D. S. Coma. P. 21.2749flssn: ‘J. K: Hdl. E. P. Bkcbmd. B. iZ.Cbakofmky.J: B. Bi$ uii W. A. Scppud, 1. Am. Ckm Ser. 93. II0 (1971):‘E. P. Bhmhnl. Jr.udA.~BI+I,ltT(l~:‘M.~R.N. Wik G. w. Glnbmmd IJ. Roy,Jbidw 2752wm,. ‘It. W. Cox. N. D. Humomy.G. Ndm madK. B. Wiberg.1. csem.F&y&66. IN mm. ‘II. D. Newtonmd J. M. Bchdmm.1. Am. Chm. Sk 94.767 (1972). sMmdzR#wopat7kckllI~of#ukeJe&p.461. Wiky. New YaL (l%5). ‘R. N. R& G. C. Tcsoroml D. R. Moore.J. Gvg.C&m. 32 1.91(I%7). t. K. I&d ud W. 1. Powll. 1. clnr. Ser. 119.I976 (1921). ‘J. W. Cmmp.1. arc. Chm. 21.933 (1%3). a A. Butch. Ace. Oar Ra. 6, m (1973):E. Bsioccbi R. Rtudwei~sc~I.cLIIII.soc.PefkinII.436(I977). “SDhkfakymdR.K.~I.AmCkt.Sor.97.3239 (1975):‘A. B. !Mb md R. M. !hbom@. Jr.. Tetmhdma L&UI l6@ (19n): ‘W. E. Tmce ud L B. Liody. 1. N. cmm. y 1463(l%l). ~.HmaIsdS.HPail.I.ArrCYwrr.S#.%,6122(19n). “K. B. Wibem K. s. Pekrs, G. B. EBiumud F. ARmi. /bid
. -
purhlbythemmmivik
mllre.“baepuhaiatochmdr/wimomwstadtbdr . . . dclltBaboaiarbo~“Tbcc&lad_irawnd skopmpox~ebkmaaubaihJc-by~ rcmioatimcs~ytothcOk NNRrpechrradGC . . damtms Pa tma~Sixyc~ NMR CCDCIJ) b: b I.13 (6 6H). 24s (a&4HA 2% (111, IH), 3.3(m IH) uul 4.3 (q. IH). (portad:C. 66% H, 9.27; N. 10.20.Cdc. C. 69m H. 9.33;N. lO.U7%).Fa the clr kmcr NMR (CDC&)6 1.1s (d. 6H). 21-26 (a, JH). 3.3 (a. IH) rad 3.9 (a. IH). ;Fg; C. 6&92;H. 9.53;N. 10.24.Clk. C. 69.06;H. 9.35;N. Kiwic~Baocksohsoftbe~~ in&mdstmdwd@ip&aylforreacahswitbIradubolwRb2)
99.3946ml. “CkmkdRemMtyadRcatkmPathsfEdaadbyG.Kbpau). Wiky-htemdmm. New Yak 11971):R. F. Hmdsor~. A&w.&uIsrEd.li36(I973). .. ‘O.W.OoLcLc.~Liom.~.P.HvrbrsdF.~.~oolr.I.~a. cam. 1). 2445 w74~. ‘9. ikllyba Buff.s#. ckm. Be& 31.223 wz2). “N. tivseh.N.Sc.Tbeak,Bar-lhnUivenity (1978).