The synthesis of 3-methyl-2-:(3-rpentynyl)-2-cycloheocenyl
p-nitro1benzoa1te is desc["ibed. This ester so1lvolyzes in 97°/o
CF3CH20H at 2'5 °C without n-participa:tion of the CC trLple
bond, showing solvoiysis rate retardaition in comparison with
the saturated anafog. This result is e~piained by electron-withdrawing
inductiove e1ffect 01f 1the CC trirple bond. The lo.g k va~ues
of alkanyl- (4), alikenyl- (5, 6), and alkyny:l-substitJu·ted (10)
esters show good linear correia1tion With the pK. values of the
cOirresrponding car:boxyJ'ic acids

Borčić, Stanko

Ladika, Mladen

Sunko, Dionis E.

University of Zagreb Repository

Solvolysis rate of 3-methyl-2- (3-pentynyl) · 2-cyclohexenyl p-nitrobenzoate. A model system for n-participation of the CC triple bond

The synthesis of 3-methyl-2-:(3-rpentynyl)-2-cycloheocenyl
p-nitro1benzoa1te is desc["ibed. This ester so1lvolyzes in 97°/o
CF3CH20H at 2\u275 °C without n-participa:tion of the CC trLple
bond, showing solvoiysis rate retardaition in comparison with
the saturated anafog. This result is e~piained by electron-withdrawing
inductiove e1ffect 01f 1the CC trirple bond. The lo.g k va~ues
of alkanyl- (4), alikenyl- (5, 6), and alkyny:l-substitJu·ted (10)
esters show good linear correia1tion With the pK. values of the
cOirresrponding car:boxyJ\u27ic acids

Mladen Ladika

Dionis E. Sunko

Stanko Borčić

Hrčak - Portal of scientific journals of Croatia

CROATICA CHEMICA ACTA CCACCA 57 (3) 331-337 (1984) CCA-1448 YU ISSN 0011-1643 UDC 347,546 Original Scientific Paper Solvolysis Rate of 3-Methyl-2- (3-pentynyl) · 2-cyclohexenyl p-Nitrobenzoate. A Model System for n-Participation of the CC Triple Bond Mladen Ladika, and Dionis E. Sunko Department of Chemistry, Faculty of Science, University of Zagreb, 41000 Zagreb, Croatia, Yugoslavia and Stanko Borcic Faculty of Pharmacy and Biochemistry, University of Zagreb, 41000 Zagreb, Croatia, Yugoslavi'a Received December 19, 1983 The synthesis of 3-methyl-2-:(3-rpentynyl)-2-cycloheocenyl p-nitro1benzoa1te is desc["ibed. This ester so1lvolyzes in 97°/o CF3CH20H at 2'5 °C without n-participa:tion of the CC trLple bond, showing solvoiysis rate retardaition in comparison with the saturated anafog. This result is e~piained by electron-with-drawing inductiove e1ffect 01f 1the CC trirple bond. The lo.g k va~ues of alkanyl- (4), alikenyl- (5, 6), and alkyny:l-substitJu·ted (10) esters show good linear correia1tion With the pK. values of the cOirresrponding car:boxyJ'ic acids. INTRODUCTION Calt'ionic polyene cyclizations were ex'tensively investligated durilng the last two decades and biomimetic syntheses of various terpene- and steroid--Uke compounds were developed1• However, the question orf mechanism of these reactions is strn open to debate. H is not certailn whether two or more rinigs are formed in a concerted manner or whether the polycycliza-tion is a stepwise process proceed'ing through one or more partially cycli-zed ilntermed:ialtes. According to Johnson, ra at present time the balan.ce is somewhat Ln favor .of the former, while some cogent arguments in favor of the lrutte-r have been presented by van Tamelen.2 TheTe are very few examples where either the concerted3•4 or the stepwise5 nature of these reaeitions has been unequivocalJy demonstrated. AllyUc cations have been extensiverly used as initiators in biomimetic olefinic polycyclie;artions.1• Thus acid cataly2ied heterolysis of the C-OR' bond in 1 leads to estrone derivative 2. Since the ra·te of formation of 2 from 1 depends3 upon the naiture of the su:bstituent R, it appears that this reaction proceeds by way of extended n-par·t'icipation, i.e. the formation 332 M. LADIKA ET AL. of both new rings is concerted with the breaking of the C-OR' bond. In this particular case an allyl cation is not formed in lthe rate determining step as a discrete intermediate. R 1. This remarkable observation led us to an invesitigation of possible :n:-participaUon 'in the mode[ system 3 which resembles 1 in that the cyc-lization initiator is a potential endocyclic allyl cation. This 1resemblance appears clearly if formula 1 is drawn as in 1a. R' R" H~ ~ OR' ~ .!.!!. a, R• D, R'• H R" • -CH2CH-O b, R =CD3 , R'• CH3 R Acid catalyzed cyclization of 3 yielded products with an even distri-but'lon of the deuterium label between the two aUylic positions.6 It was concluded ,that here cyclization occurs a.fter the rate determining forma-tion of an allylic cation intermediate. In continuation of th'is worik, we recently reported7 on rates and tx.-deu:terium kine1ti 0 J.~otopP. efd'ect.s (KIE) in solvolyses of p-nitrobenzoaites 4-6. w OPNB w OPNB w OPNB .1. .l!.. ~ The rates of 5 amd 6 were reduced with respect to that of the refe-rence compoUIIld 4 both 'in 80-0/o v/v aqueous ethanol and in 97{)/o w/w aqueous 2,2,2-trifluoroethanol although extensive cyolization occured 1in most cases. In accordance with these resu:lts secondary tx.-deuterium KIE measured with 5 and 6 were very similar in magnitude to those obtained with 4 and near the maximum value. Thus both, relative rates and KIE, unambLguously prove that :n:-electrons of the alkenylic side ciha'Ln :do not pa:rtic'ipate in the rate determining step of the investigated solvolyrt;ic reac-tions and that resonance-stabilized allyUc cations are formed as first intermediates. n -PARTICIPATION OF CC TRIPLE BOND 333 It seemed puml'i!Ilg that no simple :ii-participation occurs in cationic reactions of 3, 5 and 6 while extended n-par,ticipation is observed in an ana'logous reaction with 1. The behavior of 2-alkenylcyclohex-2-enyl deri-vatives seems even more peculiar in view of the fact that acid catalyzed cyclization of 78 and epoxide ring opening with 82 as well as the solvolysis od 99 all occur with n-part'icipation. L Therefore fur1ther investigation of cationic reactions wtth suibstraites related to 3, 5 and 6 seemed warranted. Herewith we report solvolysis rate Of 3-methyl-2-{3-pentynyl)-2-cyc,lohexenyl p-nitrobenzoate 10. I QJ OPNB 10 Su:bstttuted acetyJenic groups have been used as terminators in bio-mime1tic olefinic polycyclizations so as to form directly the five-membered D ring of steroid precursors.1a,b,io,n It was observed :that the stereoselecti-vity of the C/D ring junction was less pronounced with acetylenic than with the corresponding olefinic terminators.10•11 Smaller steric requirements of the former relative to the latter group was mentioned as a possible explanation of this observation. Another factor which was considered is a difference in the angle of a·ttack on the sp1 vs. sp2 carbon by the cationic center.11.12 These observations led us to the belief that 10 might behave differently upon solvolysis than the olef'inic counterparts 3, 5 and 6. It also seemed reasonable to consider the possibility of :n-participation with 10 since it was shown that the tendency of the triple bond to participate slightly exceeded that of the double bond in solvolyses of 6-hepty.n-2-y,l and 6-octyn-2-yl tosylates and their olefinic analogues.13 It was also shown that triple and double bonds show a similar nucleophilic activity rt-Owards vinyl cations.14 The nucleophilicity of a CC triple bond towards external electrophiles may be as high as or higher than that of a double bond. In these reactions relartive rates of pairs of equally sUlbstituted olefins and acetylenes, k 0 /ka, have been repor.ted to range from 108 to 10-2, depending mainly on the nature of the ele1ctrophilic reagent but also on the structure of the unsaitura1ted sUibstrates and, in some cases, on the solvent.15 RESULTS AND DISCUSSION The ester 10 was synthesized by appropl'iate modifications7 of stan-dard procedures,16•17 according to Scheme I. 334 M. LADIKA ET AL. ¢r· 0 I NaH ID HCONM92 et,__) cXJ 0 11 PNB • p-n;frobenzoyl I QJ H OPNB 1Q. Sciheme I. KOH EtOH PNBCI ~ (j( ~ H~ Ester 10 wa'S solvol~ed ilrl 97% w/w aqueous 2,2,2-trifJ.ooroethanol (TFE) at 25.00 ± 0.05 °C. The clear first-order kinetic behavior was obser-ved and the following rate C·Ons,tainrt; was determined (the uncertainty is the standa,,rd deviation of the mean) : k = (7.27 ± 0.02) x 10--4 s-1 In Figure 1 the r-ate constants of soh~oaysis of esters 4--6,7 and 10 are compared with the pKa values of cariboxylic acids 14,18 15,19 16,19 and 17.ro log k+ 4 1.3 1.2 1.1 1.0 0.9 o 0.8 3,4 3.6 R---CHzC02H 14, R = CH2CH3 15, R = CH = CH2 16, R = CH = CMe2 17, R = C == C-CH3 3.8 4.0 4.2 0 c 4.4 B 0 4.6 4.8 5.0 pKa Figure 1. P:lot of lo.g k values for soilvolysis 01f esters 4 (A), 5 (C), 6 (B) aind 10 (D) in 97010 w/ w CF3CH20H at 25 °C .against ionwaition c·onstalllts oJ' acids 14 (A), 15 (C), 16 (B) and 17 (D). ;>i'-PARTICIPATION OF CC TRIPLE BOND 335 our result show:s ithait the solvolysis of ester 10 is sloiwer than the solvolysis of 2-butyl-substttlllted ester 4, and also than the oolvolysts of 2-alkenylic esters 5 and 6. This resuJ.t can be explained in general by electron-with-drawilllg ililductive effect of a CC t'ri'ple bond in es,ter 10, Which is even stronger tham. inductive effects of alkenylic bonds in side chain of esters 5 and 6. These inductive effects of 2-alkenyl and 2-al'kynyl substituents in esters 5, 6 and 10 can be compared with the indU'ottve influe:nce of the same su:bstituents on pKa values of carboxyUc acids 15-17 (Figure 1.). The plait (log k + 4) vs. pKa shows sat~sfactory linear correlation (the correl1at'ion coef'ficient is 0.977). I 001 I , , 18 The obtained rate cons,tant of ester 10 is in keeping with the propo-sed stepwise mechanism of solvoly:sis, according to which the n-pa1itici-pation is not revealed in this reaction, and the resonance-staibilized ally-lic cation 18 is the first formed intermediate. EXPERIMENTAL SECTION Infrared spectra were recorded on a Perkin-Elmer 167 spectrometer. 1H N.MR spectra were rooordled Olll a Viaruan T-60 tnis.trumenit. All commercial :rie,ag·ents were ACS reagent grade. 3-Methyl-2-(3-pentynyl)-2-cyclohexen-1-on.e (12) Ethyil 2-methyl-4-keto-2-cyc.1ohexenecirurboxy1ate21 (3.72 g; 20.41 mmol) was added d.roipwise ito a cold (0 °C) suspension o,f NaH (490 mg; 20.42 mcrnoJ) .ilil 17 ml of N,N-dimethylformamide. The resulting .,mixture was stirred and heated (60 °C) .ilil nibr(}lgen aitmosphere over a 12-h period. The mixture wias 'then co:oled to 0 °C, 5-bromo-2-·pentyne22 (3.00 g; 2-0.41 mmol) was added and the resulting mixture was stirred and heated (90 °C) in nitrogen atmosphere over a 12-h pe-riod. The reaction mixture was then diluted with water and extracted with diet-hyl ether (3 X 20 ml). The combined eitheral layers were dried with anhydirous Na2S04 and the solvent was remo·ved on a Btichi rotary evaporator to give the crude alkylated ketoester 11 (5.13 g) which was used in further synthesis without additi,onal purfication. · ALkylated ketoester 11 (5.13 g) was added to a solution of KOH (2.14 g; 38.1 mmoO dn anhydrou,s ·e,thamol (15 ml). ReaCiti,on mi:xiture wias stirred and iI'e'fliuxed in nitrogen atmosphere over a 20-h period. After evaporation of solvent, the re-sidual darik OiLl was dliluted Wiith water and exitiracted wdth diethyl ether (3 x 20 ml). The combined etheral layers were dried with anhydrous Na2S04 and the solvent was removed on a Btichi rotary evaporator. The residual crude ketone was purified by colurrnn chromatography on silica gel, using mixture benzene--diethyl ether 8 : 2 as ·the e1uenit. Th:is procedme gave ketone 12 (l.32 g; 36.7% ) which was homog.en,ous on ,thin-layer chrOIIllato,graphy. m (neat, NaCl) : 6.01 µm (C=O). 1H-N.MR (CCl4, internal Me4Si) o 1.74 (3H, s, C - C-CH3), 1.70 (3H, s, C=C-CH3) . 336 M. LADIKA ET AL. 3-Methyl-2-(3-pentynyl)-2-cyclohexen-1-ol (13) The .so1ution of ketone 12 (163 mg; 0.9·25 mmol) m anhydrous diethyl-·et\her (3 ml) was added dropwise to the suspension of LiAlH4 (185 mg; 4.87 mmol) in anhycfilio1us diethyl e•ther (8 ml). The reacltion mix;ture was stirred 2 hat room tem-perature. After that, 3 ml of water was added, etheral layer was separated and the res~dual slrurry was ex•tracited wilth diethyl either (3 X 10 ml). The combined etheral layers we.re dried wilth 3.IIlhydxous Na2S04 a!Illd :ether was eva.pora;ted llio give alcohol 13 (154 mg; 93.4°/o) which was homogenous on thin-layer chroma-tography. IR (neat, NaCl): 2.98 µm (0-H). 1H~NMR (CCl4, internal Me4Si) o 3.93 OH. br.s., 0-C-H), 3.06 OH, bir.s., OH), 1.71 (3H, s, C = C---CH3), 1.65 (3H, s; C = C---CHJ), 0.60-2.43 (10 H, a.bsorption o[ residual protons). 3-Methyl-2-(3-pentynyl)-2-cyclohexen-1-yl p-nitrobenzoate (10) Sol!Ult.i·on of alcohol 13 (126 mg; 0.707 mmo'l) and p-:n.itrotben21oyl chloride (550 mg; 2.96 mmol) in anhydrous pyridine (8 ml) was stirred for 3 days at room tem-perature. The mixture was then poured on ice and extracted with pentane (5 X 10 ml). The combined pentane extracts were dried with anhydrous Na2S04, solvent w:as evapoira.ted and the reslli.u·al crude product was purified on a silica gel column using mixture pentane-benzene 9 : 1 as the eluent. The yellow oily crystals of ester 10 were obtained (207 mg; 89 .. 5~/~). This product was homoge-nous on a thin-layer chromatography. IR (neat, NaCl): 5.81 (C0---0---C), 6.211 (C=C), 6.52 and 7.41 (N02), 9.03 (C-0) and 13.79 µm (Ar-H). 1H-NMR (CGl4, internal Me4Si) o 8.14 (4H, s, CsH4N02-p), 5.56 (lH, br.s., 0-C-H), 1.79 (3H, s, C =:c-CH3), 1.68 (3H, s, C=C---CH3), 0.70-2.45 (10 H, absorptilon of residual pro-tons). Kinetic Measurements The titrimetric rates were obtained using the automatic potentiometric ti-tration method by means of a Radiometer, Copenhagen, automatic titrator T'IT2 w1th autob:urette ABUll and ti·trigra;ph SBR3. Thie substiraite concentraition was 6-7 mg in 15 ml of solvent. The solution for titration was 0.02 M NaOH in 970/o TFE. Seven solvolyses of ester 10 were performed and the rate constant was cal-culated using a nonlinear least-square sum-fitting pro.gram. Acknowledgment. - We are grateful to Professor MichaeI Hanacik from the University o.f Ttihingen for a gHt of 3-pentyin-1-ol. REFERENCES 1. For review see: a) W. S. J o h n s on, Angew. Chem. Int. Ed. Engl. 15 ( 1976) . 9; b) W. S. Johnson, Bioorg. Chem. 5 (1976) 51; c) W. S. Johnson, Acc. Chem. Res. 1 (19.68) 1; d) E. E. van Tame 1 en, Acc. Chem. Res. 1 (1968) 111; e) E. E. v a ill Tame 1 en, Acc. Chem. Res. 8 (1975) 152. 2. E. E. van Tame 1 en and D.R. James, J. Amer. Chem. Soc. 99 (1977) 950. 3. P. A. B art 1 et t, J. I. Br au m an, W. S. Jo h n s o ill, and R. A W o 1 k-m an n, J. Amer. Chem. Soc. 95 (1973) 7502. 4. 0. Kronj a, E. Poll a, and S. Borcic, J. Chem. Soc., Chem. Commun. (1983) 1044. 5. G. S ·toi'k and AW. Burgstahle ·r, J. Amer. Chem. Soc. 77 (1955) 5068. 6. M. Ladika, I. Bregovec, and D.E. Sunko, J. Amer. Chem. Soc. 103 (1981) 1285. 7. M. Ladika and D. E. Sunk o, Croat. Chem. Acta 57 (1984) 179. n '-PARTICIPATION OF CC TRIPLE BOND 337 8. R.P. Linstead, A. B.L. Wang, J.H. Williams, and K.D. Erring-ton, J. Chem. Soc. (1937) 1136; W. S. Johnson, S.L. Gray, J . K. Ctr an-d a 11, and D. M. Bai 1 e y, J. Amer. Chem. Soc. 86 (1964) 1966. 9. I. Mi he 1, M. O rl o ·vi c, E. Po 11 a, and S. Bo r c i c, J. Org. Chem. 44 (1979) 4086; I . Mihel, J . siste 1k, S. Borcic, K. Humski, and D. E. Sunko, ibid. 44 (1979) 4091 ; E . Polla, S. Borcic, and D.E. Sunko, ibid. 44 (1979) 4096. 10. W. S. Jo h n s on, L. R. Hu g h es, J. A. K 1 o e k, T . Nie m, and A. Shen rv i, J. Amer. Chem. Soc. 101 (1979) 1279. 11. W. S. Johnson, L. R. Hughes, and J. L. Ca ·r ls on, J . Amer. Chem. Soc. 101 (1979) 1281. 12. J . E. Baldwin, J. Chem. Soc., Chem. Commun. (1976) 734. 13. P . E. Pete a: son and R. J . Kam a it, J. Amer. Chem. Soc. 91 (1969) 4521. 14. a) M.J . Ch and y and M. Ha ill a ck, Tetrahedron Lett. 50 (1975) 4515 ; b) Vinyl Cations, P. J. St an g, Z. Rapp op or t, M. Han a ck, and L. R. Sub ram an i an, New Yo['}{, Academic Press, Inc., 1979, pp. 123-151. 15. For a review see: G. Melloni, G. Modena, and U. Tonellato, Acc. Chem. Res. 14 (1981) 227. 16. W.S. Johnson, P.J. Neustaedter, and K . K. Schm i ege!, J. Amer. Chem. Soc. 87 (1965) 5148. 17. J.A. Marshall, N. Cohen, and A. R. Hoch s tetler, J. Amer. Chem. Soc. 88 (1966) 3408. 18. B. Sax ·ton and L. S. Darken, J . Amer. Chem. Soc. 62 (1940) 846. 19. D. J.G. Ives, R.P. Linstead, and H. L. Riley, J . Chem. Soc. (1933) 561. 20. G. H. Mans .field and M. C. Whiting, J . Chem. Soc. (1956) 4761. 21. L. I. Sm H h and G. F . Ro u au i.t, J. Amer. Chem. Soc. 65 (1943) 631. 22. J. Fl ah au it and P. Mi gin i a c, Helv. Chim. Acta 61 (1978) 2275. SAzETAK Brzina solvolize 3-metil-2- (3-pentinil) -2-cikloheksenil-p-nitrobenzoata. Modelni sistem za n-participaciju trostruke veze CC M. Ladika, s. Borcic i D. E. Sunko Opisana je sinJte,za 3-metil-2-(3-pentin.hl)-2-cikloiheksenil-p-nitrobeinzoata. Taj ester solvolizira u 97% -•tnom CF3CH20H pri 25 °C bez n-participacije trostriuke veze CC i poikazuje usporenje solvoU.ze u us1poredbi sa zasicenim analogom. Taj rezultat objaisnjen je elektron-izvlacecim induktirvnim efektorm trostruke veze CC. Poikazalo se da su vrijednosti log k za aLkanil- (4) , alkenil- (5,6) i a1kinil--siupsti.tuirane (10) estere u dobrom lineM'IIlom odnosu s pKa-vrijednostima o.dgo-varajucih ikarboiksilnih kiselina. 

Solvolysis Rate of 3-Methyl-2- (3-pentynyl) · 2-cyclohexenyl p-Nitrobenzoate. A Model System for n-Participation of the CC Triple Bond

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Solvolysis rate of 3-methyl-2- (3-pentynyl) · 2-cyclohexenyl p-nitrobenzoate. A model system for n-participation of the CC triple bond

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