Chlorides 1 (1-aryl-1-chloro-4,8,13,17,21-pentamethyl-4,8,12,16,20-docosapentaenes) with various phenyl substituents were prepared, and solvolysis rates were measured in 80% (v/v) aqueous ethanol, and in 97% (w/w) aqueous 2,2,2-trifluoroethanol. Hammett ρ+ values obtained are -2.18, -2.13, resp., suggesting a concerted bicyclization in the rate determining step

Kronja, Olga

Malnar, Ivica

Repository of Faculty of Pharmacy and Biochemistry University of Zgreb

A case of concerted formation of five and six member rings; solvolytic behavior of 1-aryl-1-chloro-4,8,13,17,21-pentamethyl-4,8,12,16,20-docosapentaenes

University of Zagreb Repository

Chlorides 1 (1-aryl-1-chloro-4,8,13,17,21-pentamethyl-4,8,12,16,20-docosapentaenes) with various phenyl substituents were prepared, and solvolysis rates were measured in 80% (v/v) aqueous ethanol, and in 97% (w/w) aqueous 2,2,2-trifluoroethanol. Hammett &rho;+ values obtained are -2.18, -2.13, resp., suggesting a concerted bicyclization in the rate determining step

Ivica Malnar

Olga Kronja

Hrčak - Portal of scientific journals of Croatia

ISSN-0011-1643CCA-2565 Preliminary CommunicationA Case of Concerted Formation of Five and SixMember Rings; Solvolytic Behavior of 1-Aryl-1-chloro--4,8,13,17,21-pentamethyl-4,8,12,16,20-docosapentaenesIvica Malnar and Olga Kronja*Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kova~i}a 1,P. O. Box 156, 10000 Zagreb, CroatiaReceived December 10, 1998; revised January 20, 1999; accepted January 28, 1999Chlorides 1 (1-aryl-1-chloro-4,8,13,17,21-pentamethyl-4,8,12,16,20-docosapentaenes) with various phenyl substituents were prepared,and solvolysis rates were measured in 80% (v/v) aqueous ethanol,and in 97% (w/w) aqueous 2,2,2-trifluoroethanol. Hammett + val-ues obtained are –2.18, –2.13, resp., suggesting a concerted bicycli-zation in the rate determining step.The solvolytic behavior of benzyl chloride 1 (1-chloro-1-pheny-l4,8,13,17,21-pentamethyl-4,8,12,16,20-docosapentaene) revealed inconsistency in some as-pects, thus the reaction mechanism is ambiguous.1 The ethanolysis rate (ku)of 1 is practically the same as the rate of its saturated analog (ku / ks = 2.5),indicating that the reaction may proceed by way of an unassisted process.On the other hand, activation parameters obtained are consistent with therate determining participation of at least one double bond, in which thehigh degree of order required in the transition state (large negative S#) isovercompensated by a rather small H#. The magnitude of S# = –122  13J K–1 mol–1 obtained with 1 in aqueous ethanol ( = 80%, 80E) is even largerthan the entropy of activation obtained for the concerted monocyclizationreaction with the referent benzylic chloride 2 (S# = –99.0  21 J K–1 mol–1),2but is lower than the one obtained with referent chloride 3 (S# = –194  12J K–1 mol–1).3 It should be emphasized that, according to all methods usedCROATICA CHEMICA ACTA CCACAA 72 (1) 115¿121 (1999)* Author to whom correspondence should be addressed.(ku/ks rate effects, activation parameters3 including activation volumes,4-deuterium kinetic isotope effects5), compounds 3 can be used as a reliablereferent for concerted bicyclization. Also, chlorides 2, except the p-metoxy de-rivative, represent confirmed referents for concerted monocyclization.In our previous communication,6 we reported that tertiary chloride 4 withthe double bond at C-4 from the reaction center, like chloride 1, has a con-siderably reduced -deuterium kinetic isotope effect in the solvolysis (both,in 80% vol. aqueous ethanol and 97% w, 2,2,2-trifluoroethanol; kH/kD=1.30)compared to its saturated analog (kH/kD=1.80). That result was attributed tothe assistance of the double bond in the rate-determining formation of thefive member ring. Therefore, the question arises whether the unassisted re-action takes part in solvolysis of 1, whether the concerted formation of the116 I. MALNAR AND O. KRONJAfive member ring occurs, or if even a concerted bicyclization takes place, i.e.whether the extended -participation mechanism is operative.We demonstrated that the value of the reaction constant (Hammett +)7can be used as a powerful tool in testing the concertedness of solvolytic reac-tions.8 Roughly, as presented in the Table, the values of + are: +  –6 whenan unassisted process occur (obtained with the saturated analog 2S of thereferent chloride 2), +  –4 when the concerted monocyclization takes part,as it is the case of the referent chloride 2, and +  –2 when the concerted bi-cyclization exists as with substrate 3. It seems that each additional doublebond that takes part in the rate determining step lowers the negative valueof the reaction constant by approximately 2 units.In order to obtain the + values for the benzylic system 1, a series ofbenzylic chlorides 1 were prepared (Y = p-OCH3, p-CH3, H, p-Br and m-Br).The parent alcohols of 1 were obtained by addition of the corresponding bro-mobenzene to aldehyde 5 (prepared according to the earlier described proce-dures1,9) in the presence of lithium. The alcohols were converted to chlo-rides, which were subjected to solvolysis in 80% (v/v) aqueous ethanol (80E)and in 97% (w/w) aqueous 2,2,2-trifluoroethanol (97T). Reactions weremonitored by titration of the liberated acid with an automatic pH-stat atthree different temperatures. All reaction rates were extrapolated to 25 °C,which values were used to calculate the Hammett + values using the sim-EXTENDED -PARTICIPATION 117TABLELinear Free Energy Correlation of Some Benzylic Chlorides at 25 °CCompound Solventanb+crd2S 97T 5 –6.28  0.25 0.9972 97T42–3.93  0.10–6.210.9983 80E97T55–1.45  0.03–1.76  0.040.9990.999480E97T55–1.81  0.05–1.56  0.040.9990.999180E97T55–2.18  0.07–2.13  0.070.9980.998a80E is aqueous ethanol ( = 80%); 97T is aqueous 2,2,2-trifluoroethanol (w = 97%);bNumber ofdata points with (n = 5) or without (n = 4) the rate of the p-anisyl derivative. n = 2 +was ob-tained from p-anisyl and p-toluyl derivatives;cUncertainties are standard errors of estimate.dCoefficient of correlation.ple regression analysis. The results are presented in the Table and in theFigure, together with some other important referent data.The values of + for chlorides 1 obtained in both solvents, 80E and 97T(different nucleophilicity), are essentially the same, excluding the possibil-ity that this significant result is due to the rate determining displacementby the solvent.10The reaction constant is generally considered to be the measure of thecharge »seen« by the aromatic ring at the reaction center, which is closelyrelated to charge delocalization. If -participation of the neighboring doublebond(s) occurs, the charge is delocalized from the reaction center, and thusthe lower negative + value is obtained. The Hammett + values obtained inboth solvents (+ = –2.18 in 80E and + = –2.13 in 97T) unambiguouslydemonstrate that -participation occurs in the rate determining step with118 I. MALNAR AND O. KRONJAFigure. Hammett ++ plots for some benzylic chlorides in 97% (w/w) aqueous2,2,2-trifluoroethanol.chlorides 1. Even though the negative values of + obtained are slightlyhigher than those of referent 3, they are drastically lower than the + ob-tained for concerted monocyclization with chloride 2, indicating that thetransition state has less positive charges on the benzylic carbon than a sim-ple bezylic carbocation. The latter conculsion demonstrates that this cannotbe an unassisted solvolysis, and may suggest that the concerted bicycliza-tion may take place with substrate 1.As it was shown earlier, the concerted monocyclization was proved forall derivatives of 2 but the one with the p-methoxy group. In the case ofp-anisyl derivative, the participation of the neighboring double bond iseliminated by the strongly electron donating p-methoxy substituent. How-ever, both, the coefficient of correlation (r) and the statistical test 11indicate that the p-methoxy variant of 1 should be included into correlation(Table). The facts that drastically different reaction constants were obtainedwith 1 than with the model for the concerted monocyclization 2 (–2.13 vs.–3.93 in 97T), and that the p-methoxy derivative solvolytic behavior is dif-ferent than that of 2, are in accord with a previously drawn conclusionabout the possible concerted bicyclization.Since the structure of chloride 1 is closely related to the squalene de-rivative 6 (the structures differ in one methylene group), it is advantageousto compare the + value obtained with the corresponding reaction constantof chloride 5. For the latter, extended -participation mechanism was estab-lished not only on the basis of the Hammett + value,9 but also on the basisof lack of the -deuterium kinetic isotope effect obtained with the tertiarycounterpart of 5.12 The behavior of the two species is almost the same in sol-volysis and is comparable with the referent chloride 3. Both have a similarreaction constant in magnitude, and also in both cases the electron donationof the p-methoxy groups does not cancel out the assistance of double bonds.Probably the most obvious support for the possible extended participa-tion mechanism of 1 comes from the careful study of the superimposedHammett plots presented in the Figure. It is evident that, according to theslopes of the plots, three different mechanisms can be traced down. Break-down of the linear relation occurs with the plot that corresponds to chlo-rides 2 when the mechanism is changed from concerted monocyclization tounassisted reaction with the p-methoxy derivative. The plot obtained afterthe breakdown caused by the p-methoxy variant is almost parallel with theplot obtained with 2S, which also reacts with the lack of the neighboringolefinic bond participation. It can be seen that the slope of the Hammettplot with all derivatives of 2 (Y=CH3, H, m-Br, and p-Br, resp.) but themethoxy variant is drastically less steep, indicating the concerted monocyc-lization mechanism. Further profound decrease of the slope occurs for allEXTENDED -PARTICIPATION 119three other compounds: the investigated chlorides 1, the referent chlorides3, and the squalene derivatives 6, respectively, suggesting that they all pro-ceed by way of the extended -participation mechanism.Slightly larger –+ of chlorides 1 than of the referent chlorides 3 can berationalized in terms of the distribution of the charge if the »earlier« transi-tion state of 1 is considered. In that case, the concentration of the positivecharge on the reaction center is somewhat larger than in the case of 3, inwhich the transition state is more akin to tertiary cyclohexyl cation. Onceagain it has been proven that only a large rate effect can be taken as a proofof the neighboring group participation13 Moderate, as obtained with 1(ku/ks=2.5), or even inverse rate effect can conceal some considerable partici-pation that can be proven by other methods.Acknowledgement. – We gratefully acknowledge the financial support of thisresearch by the Ministry of Science and Technology of the Republic of Croatia (GrantNo. 006151).REFERENCES1. O. Kronja, S. Bor~i}, K. Humski, and C. S. Foote, Croat. Chem. Acta 63 (1990)193–201.2. I. Mihel, M. Orlovi}, E. Polla, and S. Bor~i}, J. Org. Chem. 44 (1979) 4086–4090.3. O. Kronja, E. Polla, and S. Bor~i}, J. Chem. Soc., Chem. Commun. (1983) 1044––1045.4. N.-h. Ho, W. J. le Noble, J. Org. Chem. 54 (1989) 2018–2021.5. S. Bor~i}, K. Humski, V. Imper, O. Kronja, M. Orlovi}, and E. Polla, J. Chem. Soc.,Perkin Trans. 1, (1989) 1861.6. S. Bor~i}, O. Kronja, K. Humski, and S. Mileti}, Croat. Chem. Acta 69 (1996) 563.7. For reviews, see: (a) N. Isaacs, Physical Organic Chemistry, 2nd Ed.; Longman:London-Singapore, 1995, pp. 146–192, 451–455, 650–654. See also: (b) Ruasse,M.-F.; A. Argile and J.-E. Dubois, J. Am. Chem. Soc. 106 (1984) 4846–4849. (c) L.P. Hammett, Physical Organic Chemistry; McGraw Hill, New York, 1970.8. I. Malnar, K. Humski, and O. Kronja, J. Org. Chem. 63 (1998) 3041–3044.9. S. Bor~i}, K. Humski, O. Kronja, and I. Malnar, Croat. Chem. Acta 69 (1996)1347–1359.10. J. M. Harris, F. L. Schadt, P. von R. Schleyer, P. von R, C. J. Lancelot, J. Am.Chem. Soc. 91 (1969) 7508–7510, and reference cited therein.11. O. Exner, Collect. Czech. Chem. Commun. 31 (1966) 3222–3227.12. O. Kronja, M. Orlovi}, K. Humski, and S. Bor~i}, J. Am. Chem. Soc. 113 (1991)2306–2308.13. M. Orlovi}, S. Bor~i}, K. Humski, O. Kronja, V. Imper, E. Polla, and V. J. Shiner,Jr., J. Org. Chem. 56 (1991) 1874–1878.120 I. MALNAR AND O. KRONJASA@ETAKPrimjer uskla|enog zatvaranja petero- i {estero~lanog prstena; solvolitskopona{anje 1-aril-1-klor-4,8,13,17,21-pentametil-4,8,12,16,20-dokosapentaenaIvica Malnar i Olga KronjaPripravljeni su kloridi 1 (1-aril-1-klor-4,8,13,17,21-pentametil-4,8,12,16,20-doko-sapentaeni) s razlicitim supstituentima na fenilnom prstenu. Izmjerene su konstantebrzine solvolize u 80% (vol./vol.) vodenom etanolu te u 97% (w) vodenom 2,2,2-tri-fluoretanolu. Dobivene Hammettove vrijednosti + od –2,18, odnosno –2,13 upu}ujuna uskladeni proces ciklizacije dviju dvostrukih veza u stupnju koji odreðuje brzinureakcije.EXTENDED -PARTICIPATION 121