What is the IUPAC name of CH3COCH2CH2COOH

Contribution to the chemistry of substituted γ-lactones

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1 Reserch Cllectin Dctrl Thesis on chemistry he substituted γlktne Authr (s): Szücs, Dezsö Ljs Publictin Dte: 963 Permnent Link: Rights / License: In Cpyright NnCmmercil Use Permitte This pge ws generte utmticlly upnct wnl frm the ETH Zurich Reserch. For mre infrmtin plese cnsult the Terms for use. ETH Librry

2 Prm. No. eitrg for chemistry he Substituted 0 Lktne Vn he EIDGENÖSSISCHEN TECHNICAL UNIVERSITY IN ZURICH for the acquisition of a PhD thesis in teinischen sciences approved PROMOTIONSAREIT submitted by DEZSÖ LAJOS SZÜCS ipl. Ing.Chem. ET.E Ungrischer permanent speaker: Mr. Prf. H. Zllinger Speaker: Mr. Prf. Dr. H. Hpff MikrkpieVerlg Munich 963

3 Ftnii: Mikfkpi «G.m.b.H. Mnien 2, Wecnifr. 4th

4 Wimet to my dear Fru

5 To my dear teacher, Mr. Prf. H. Zllinger, if I would always like to approach myself and my work, I would like to express my deepest interest in your interest. Thank you to Dr. 0. A. Stmm, he helps me with his legs and help while doing this work.

6 I TABLE OF CONTENTS Page INTRODUCTION TO THEORETICAL PART 2 I. Overview of the chemistry of the substituted iclctne 2 .. Properties of the theoretical part 2.2. Synthesis of the elements In the sugar acid series Cylation of ß, X unsaturated acidic acids Cylation of Hyrxy and fatty acids Cylation of oleic acids Some special cases. 3. Abburectins it tflktnringes Reuctive splitting Oxytiver Abbu With special rainy agents 5.4. Ismeric er YLktne 7 II. Synthesis of a "6Lktns us en (cis + trns) ß-enzylienbutyuttersäuren (IV) 20 II .. Ensuring erknstitutin er starting products (IVA and IV) 23 III. Explanation of the institute es JfLktns (VA) 24 A. Chemische eweise 24 .. Synthesis of methyl phenylbutyrlctn (VI) O.Methyl kphenylbutyrlctn (XXII) 27 III..3.! FMethyl «phenylbutyrlctn (mni) 28 III..4. / ^ Methyl /) phenylbutyrlctn (XXXVH) Figure and ring opening of the YLktne ( VA) and (VI) 38.Spectral scopes 4 IV. Considerations about the mechanism in both cases 45 V. Synthesis of further ß, f l-substituted lines 48 Vl Y (p-methxy) phenylf) methylbutyrlctn (LIV) 48 V.2. ( itert.utyl phenylbutyrlktn (LXVl) 5

7 II Page EXPERIMENTAL SECTION 55 GENERAL REMARKS ON EXPERIMENTAL SECTION 55 I. ßMethyl Vphenylbutyrlktn (VA) us en (cis + trns) ft enzylienbuttersäuren (IVA) and (IV) 55 II. SsMethyl} fphenylbutyrlktn (XV) us er ßenzylbuttersäure 59 III. Ensuring the synthetic (ice + trns) enzylienbutyric acids (IVA) and IV) IV. Abbu es ßMethyl Jfphenylbutyrlktns (VA) 62 V. Abbu es ßMethyl} (phenylbutyrlktns (VI) 64 VI.Synthesis of methyl typhenylbutyrlktns (XXII) 65 VII Synthesis of methyl phenylbutyrlktns (XXVII) 67 VIII. Synthesis of methylphenylbutyrlktns (XXXVII) 68 IX. Synthesis of 3-methyl-phenyl, 4butnil (XLVIII) 75 X. Synthesis of (pmethxy) phenyl-methylbutyrlktn (LIV) 77 itert.utyl Yphenylbutyrlktns (LXVII) 8 SUMMARY 85 6

8 INTRODUCTION As has been done, the cyclization results in it is untrnsenzylienbutyric acid nh dtt un not expected 3-methylinphthl, but a compound which, according to analysis and physicochemical data (UV, IR) (methyl% phenylbutyrlctn, could be an independent synthesis I found that methyl-8-phenylbutyrlctn produced in a proper way is not compatible with the compound obtained from Stmm. In order to explain this discrepancy, an intramolecular rearrangement would already have been carried out by Stmm during the cyclization In the synthesis of positionally inconsistent assumptions for the purpose of comparison with the unknown connection and clarification of the institute, it should be mentioned that attempts to switch to a positionally inconclusive affair in the case of cyclic acidification are to be taken from the result of this work. The Abbuversuhe resulted in the connection made by Stmm and Dtt un ghi a ß Methy l is phenylbutyrlktn. ONLY spectra show that with this representation two geometric ismers arise in a smaller ratio than with the synthesis. ) O.A. Stmm, PhD student, sel 957 2) H.H.sshr, Clb AS, sel

9 THEORETICAL PART I. Overview of the chemistry he substituted ^ functions I.l. Properties of the links The links represent stable neutrals, and their neutralization with the hydroxy fatty acids we prefer to each other conversion. In a typical solution, the link ring can be opened with the help of a phyrxyrbxylts, which s builds back on acidification. These properties can be used to purify the skin by taking it in an aqueous rium hydroxyl solution, an excess of n rium hy rxy falls with Khlenixy and is filtered after it is filtered off. saponified; The rectin curve corresponds to that of a five-chain ester (A, 2Uehnismus). CH2 CH2 I m. 0 CH2 H206 HOCH2CH2CH2C008H {]) il 0 Wheeler and Gmble investigated the saponification rate of some substituted substances in cold solutions. 3) A. Winus and F. Klänhrt, he. eutsch, formerly Ges. 54, 58 (92) 4) F. A. Lng and L. Friemn, J. Amer. Chem. P. 73, 3692 (950) 5) O.W. Wheeler and D.S. Gmble, J. Org. Chemistry 26, 322 (96)

10 3 The sterling influence of the substituents in, ß and Jf position helps to express itself. The results correspond to our knowledge of steric influence 6) in the saponification of esters after. 2Mehnlsmus. The saponification swirls are sufficient to allow them to be titrated climetrically. With an excess of alklihyrxy, the equilibrium between XLktn and JfHyrxycrbxylt is completely settled on the side of it, and excess alkali can be titrated back. In extreme cases and in the case of vermins, any excess of mineral acid can be isolated in the free oxyric acid (see, for example, thyryxy! fmethyl! fnphthylbutyric acid). Traces of a mineral acid suffice to initiate the solution. In addition to clear saponification, it can also be opened by mineral acids. There is always the risk that when using hydrogenated acid, the XHyrxyl group nucleophile is covered by a membrane (2), as shown by Pttisn and Suners in the case of ß, (i Dinethylbutyrlktm CH3CH3ÇCHH2 Ç2H3). CH3 CH3ÇÇCHH2 Ç2H3 \ c2 / II 0 CH3 6) CK Ingl, Structure n Mehnism in Orgnic Chemistry, Crnell University Press, Ithc, pp. 754, 953 7) H. Jhnssn and H. Sebelius, er. eutsch, formerly Ges. 5 ,, 480 (98) 8) V.S. Jhnsn, A. Glmn and Tf. P. Schneier, J. Amer. Chem. P. 67, 357 (945) 9) F. L. M. Pttisn un.c. Suner J. Chem. S

11 (950), Chem. Anl. Thelen, C.J. un uckles R.E. 2) (company publication) Drmstt AG, Merck E. grphie, PpierChrmt un DUnnshiht for staining agents 2) 64 p. 960 Lnn, utterwrth Spectrscpy, InfrRe Prcticl t Intructin Crss, A.D.) (952) 3929 J_4i Sc. Chem. Amer. J. Newmn, M.S. un Grrett A .. Lenlng, K.L. 0b) Sc. Chem. Sircr, J. S.S.G. 0) only those which contain similar functions, which are substituted, are produced. Mleküls it part authoritarian unconditionally not small, a pale JjLktn a enen with Sterie), (z .. connections in the overtones nturnurmeen ntur in you only small s. To llterturUverlht completely one un details in the case of these rhythms There is too much to do with the area Ds J3 (3) Fe NHO OH y \ iii cccc ^ 0 probably he complex, rtviletten has a xm acid 2). (3) Structure rtvic an xmsäure Hyrgebileten Hyrxylmin un Lktn us he with gives ri EisenIIIchl Ds sprayed. Iron III solution one with a short and one Hyrxylmu solution one with Chrmtgrmme mn ß, iflktne he hhrmtgrphie) Dnnnshihtun (Ppier Nchweis chrmtgrphische der 2) Lktne. ten ill v saturation chrkterized rn) 760 (780 iv 5.68 5.62 at absrptin level Sharpness The outstanding spectral spectrum is suitable for the analysis of the qulittive preparation process.0) i0b) its speed consists in connection classes at s between the greatest differences The r. Acid esters, ffen-chained, have an iflktne o make green in the 4

12 s methyl, phenyl, tert.utyletc. Groups make it own filges. n different At this point we would like to point out the green number, which contains a compilation of literature on ÎfLktne..2. Synthesis of the Lctne ïi2i _ï5_é E_2H! EE ê! Ie E iè Choosing the most pronounced shows the tendency to act in the sugar acids, ie the hyroxyl groups in <*, ß, X, S un position: They are always {(Lk tne , z .. (4). 4) COOH C = 0 H OH H OH HH OH _hj H0 H0 HH (A) H OH H OH CH2OH CH90H DGlunsure DGluclktn. 5) The yerch thirst of tension defeats, ß 5gllerlge We have energy lnnu with their thermynmically extremely favored. Even the heterogeneity of the ring with a Vlenzwinkel 0 should contribute significantly to the rectification of tension. 3) V. Grlgnr, Trite e chimie rgnique, Mssn Pris, XI, S) E. Fischer, er. eutsch, hem. Ges. 23, 2625 (ls90) 5) A. e y e r, er. eutsch, hem. Ges. _8, 22T7 (885) W. Hüke, Theretisch Grunlgen er rgnishen Chemie, Leipzig I, p

13 6 The seldom formed flower sugar acids have a 2.2. Cjrclisierung_er ^^ x ZÎÎH 2 ëîîîs * 2_52ES 55ëHI22 Very early on, mn the "nrmle" rectin he ß, ^ unsaturated acidic acids. Fichter and Hitrbeiter eyclized fimethyl <*, ßpentenic acid in the present time much lower stability on ls resulting in a mineral acid to ßmethyltflerlktn. The prttrpe shift of the double binding in ie ß, X position wr overrschen. 9) The point is that the ismerization with 62% sulfuric acid is only possible because of the presence of alkyl substituents in this position. Rupe in the ismerization of chain-chain (, unsaturated acidic acids similar to quinline. Even with a chain-chain gel 2) Fujiwr could show 8, unsaturated acidic acid the cyclizing effect of concentrated sulfuric acid (5). CH3 (CH2) 5CH = CHCOOH CH3 (CH2 ^ CH = CHCH2COOH »CHjtO ^ feCHCH, I I (5) 0 CHj C 6) P.A. Levene and H.S. S m m s, J. ll. Chemistry 68, 737 (926) 7) F. Flhter, A. Kiefer and W. er nulli, er. eutsch, former Ges. 42, 470 (90) 8) see on C.K. Ingl, Ann. Reprts (Chem. Sc. Lnn) 24, 09 (927) ibi. 25, 9 (928) 9) R. F i t t g, Lieblgs Ann. Chem. 283, 47 (894) 20) H.Rupe, H. R n u s and W. L t z, er. eutsch, hem. Ges. 35, 4265 (902) H.Rupe, S. Pfeiffer and S. Splitt gerber, er. eutsch, chem. Ges. 40, 283 (907) 2) Kzuyshl Fujiwr (Tky Inst. Techn.), Nippn Kgku Zsshl 82, 627 (96) cited in Chem. Abstr. 56, 8549f (962)

14 7 Apparent energy consumption in oil, ß, ß-unsaturated acids by the boyhood is less than the energy gain by cylisation of ß, 0-unsaturated acids. The similarity between allylacetic acid and 60% sulfuric acid results in the following formula (6) .2223 CH2 = CHCH2CH2COOH * CH3CH CH2 0 CH2 C 0, it is noteworthy that the theretically possible solution to a problem for phenol is completely absent. From these examples it can be seen that the position of the piling has no influence on the creation of joints. Aub, if it contains permanent doubling in a Hing (Cylhexenerlvt) st. We prefer to steer each 24) implementation. Two classic routes to the synthesis of compounds via unsaturated acids are, according to Jhnsn, modified methods of ethyl esters with a ketn, and the kenstin of a liphtic ketn (er Alehys) with trubic acid. The rectins with 27) are very similar to the action of a se and are universal skills. 22) R.P. Linste and H.H. Ryn.J. Chem. S) F. W e s sel and D. Gr, mgyr Gyôgysz. Tàrs. Êrt. 4, 7 (938) Quoted in Chem. Zbl I 2702 W. S. Jhnsn and E.H. 24) H u n t, J. Amer. Chem. S. 72., 935 (950) 25) Orgnic Rectins, 6, 22, Jhn Wiley, Kew Yrk (95) 26) J. Rths and H. Zimmer, J. Org. Chemistry 24, 586 (959) 27) ÀTs se we mostly use s Klinmtert.butylt.

15 8 Based on examples, it can be shown that the rectin oil is subject to the formation of a thermodynamic effect on unsaturated crumbs. They strongly favored ring formation, in contrast to the fatty chain structure, at the same time reflects the minimal tension ratios in smooth ring systems such as cyclization of the XHyrxy and acidic acids . for synthesis The reactin of a fatty acid group in acid esters presents no experimental difficulties. The cytotoxic reaction with molecular hydrogen via nickel lysts leads to hydroxyesters. The reactin can be carried out with ambient coolant.303 An elegant method leads from the fatty acid ester to the corresponding can be achieved through the greenritin (7), which can be met if an additional substituent is required. The introduction of such a substance \ q \ w in the case of the inclusion of acid implies the destruction of the metal complex, ie the saponification of the ester grouping and the rectification. 28) L. W. Cvert, R. Cnnr and H. Aks, J. Amer. Chem. Sc. 54, 65 (932) 29) R.C. Elerfiel et l., J. Amer. Chem. Sc. 68 ", 579 (946) H.A. Schuette 30) and F. P. T. S h, J. Amer. Chem. Sc. 48, 363 (926) R. V. Christin, 3) H.C. rwn and R.H. Hixn.J. Amer. Chem. Pp. 69, 96 (947) 32) R.T. Arnl and J.S. uckley, J. Amer. Chem. Pp. 7 ^, 78 (949) 33) J. Csn, C.E. Ams, L.L. en nice and U.D. Register, J. Amer. Chem. Pp. 66, 764 (944)

16 CHCOCH2CH2COOR RMgx, h + CH3C (R) (OMgX) CH2CH2COOR »R CHjC CH2 (7)} h2 Among en kmplexed Metllhyrien sin Ntriumbrhyri, Kliumbrhyri, 36) 37 Ntriumtrlmethxybrhyri38) eren e ren mixtures according to good« elected . The X, 7isubstituted parenting situations r (8) represent an interesting specialty. When using chromic acid as an oxytic agent, we predominantly address the branching point; The resulting tertiary hydroxyl group can no longer be xyzed further, can easily be rectified. R Rs Cr03 ^ CHCH2CH2COOH RC CH, R II (8) 0 CH, K \ / 2 C tl 0 34) D.H.R. rtn un M. Mussern Cne t J. Chen. Sc, W. G. Duben, P.D. Hne 35) and W. K. yes, J. Amer. Chem. S. JJ_, 4609 (955) 36) M.D. nus, R.W. rgn and A.A. Hinckley, J. Amer. Chem. Sc. 76, 3848 (954) 37) M. Juli, S. Juli and C. Jenmrt CR. heb.sences Ac. Sci (960) 38) P. F. Wiley, K. Gerzn, E.H. Flynn M.V. S g and T.C. Qurck, J. Amer. Chem. Sc. 77, 3676 (955) C. e t, Ann. Chim. 39) G [2] 2, 293 (947) 40) R. Meyer, Liebigs Ann. Chem (883)

17 0 ïi2.iii_ iili EH2 _É2 _J.ll2i2 2222E 2225! I 25 There are different types of this ectin type known. The cooking of the glycerin acids in the coolant gives the corresponding esters can be similar in good yield with the coolant glycerin. can be reacted by heating to C. A generally useful method for the production of oil, isubstituted oils is to use oil from poor to oil via a free tube (9). R2CrCOOCH3 + RCH = CH2 RCHCH2CR2COOCH3 r (9) RCHCH, Z I I »Ds Ot rmtm es oil, dibrmbutyric acid brmls we not used during pyrolysis and gives s poor butyrlctn in 94% yield. under the same agreement, jech s fi rmtm er fi, ö dibromoproic acid ls hydrous is eliminated. This results in s Lctn er OHyrxy Ö, (i hexenoic acid (0). 4) C.S. Mrvel and E.R. irkhlmer, J. Amer. Chem. S. (5, 260 (929) F.F. llke, .. Wright and M. F. Zent y, J. Amer. Chem. P. 3, 2488 (94) 42) M.S. Khrsch, P.S. k e un S P. Fischer, J. Amer. Chem. P. 7, 055 (948) 43) H. Plieninger, er. eutsh. hem. Ges (950) 44) R. Kuhn and D. Jerhel, er. eutsch, hem. Ges. 76, 43 (943)

18 CH3CHCH2ÇHCH2COOH »CH, / \ r r 0 CH V 0 CH3ÇH ÇH (0) Ii2i5i_Some_S ezilflle Cylisbe 5Ringnhyrie can be converted to fluxes by leveling it in cold water in blood alcohol. The rm an equivalent amount of Llthiumlulnlumhyri can 46) tish to reduce 2anhyrie to ducts. This rectin is releasable. The pyrlyse he KKetrbnstturen gives W, ß er ß, X unsaturated ^ lines. The position of the double connection is uncertain, (A) and () put two more tense forms in Frmel (). CH3COCH2CH2COOH »CH3CHCH» CH3C = CH 0 CH «C> CH2 (/ V () 0 0 (A) (), on the other hand, there is a Roman substituent in the ^ position, but the length is double in the ß, X position because of it hrough Knjugtin beingten Stbllit & TSER 8) hohung ls sure weren ngenmmen. 45) H.N. Ryn.J. Chem. S) F. Teygn, K.6. Kinkel und D. T «t J en, er. eutsch, cbem. Ges. 83, 394 (950) G. PpiheuCuture, E.M. R i hrsn un G. A. Grnt, Cn. J. Res. 90 »(949) 27, J. Thiele, Llebigs Ann. Chem. 9, 44 (90) 47)

19 2 Aliphatic glycals with a primary and a secondary hybrxyl group in position 4 (2) can be xyated to tinted with copper chromium. RCHCH2CH2CH2OH OH »RCHCH2 II (2) V" 2 II 49) The yervllligeroxytin prevents the action of llylic chains of acids. (3). (3) In en Orgnic etins there is a good combination of the use and selectivity of these metals Krrer and Schneier could show that unsaturated chains can be xyated without attack of the double bond. With it being produced for heterogeneous groups of this type of rectin. 52) Winus developed an abbreviation of silver salts in the carbonic acid series. This meth is good for you synthe 48) LF Kytles un F .. Z ienty, J. Aer. Chem. S. 6J, 385 (946) 49) A. eyer and V. Villiger, er. eutsch, he. Ges. 32, 3625 (899) 50) Orgnic Rectins, 9, 73, Jhn Wiley, New Yrk, (957) 5) P. Krrer and L. 859 (947) Schneier, Helv. 30, 52) A. Winus and F. Klnhrt and G. R everey , er. eutsch, he. Ges. 55, 398 (922) cf. on Refs. 2) and 8).

20 3 table difficult to access ß, (visubstituted 8tne. Olhm53 ^ mified the experiments of Winus, in which he systematically cautious of silver salts, liphtic men and hairs under the influence of the investigated. The rectin can nh (4) as formulated Values: 3RCOOAg 2 r2> RCOOR + Rr * 3Agr * 2 C02 (A) In the case of synthetic materials, the so-called Si mniniesters (RCOOR) predominate, while synthetic materials provide salts in moderate to good yields (5).AgOOClCH ^^ COOAg + r2 »(ch2) 3CH2 +? Agr + C02 (5) 0 C = 0 52) Winus brewed to replace it rms elementres J and could prevent it from breaking down. Abburectines of the Lktnringes.3 .. Renctlve splitting The reactive opening of the Lktnringes can be carried out in two ways (6). >>) b) i i i CCCCOOH ^^ C C ^ CCCCOH l h 0 c (0H V I 0 (6) 53) J.W.H. Olhm, J. Chem. Sc

21 4 The copper chromite, prepared by Fieser for the reactin of xketic acids, was successfully transferred from Jhnsn to Lkt 55). After fittig, hydrous also reduces symptoms. In all of these cases, saturated acidic acids are formed (Abbu nch). Less energetic responses he freezes way (b) (6), where, 4dile were received. Semmler has systematically investigated the effect of nitrium cool on the i, and CO effects. The% yields in the case of urethane are far surpassed by reactin with complex metals. Lithium-aluminum hybrids are extremely selective in reducing the effects of ene, dilene. The effects of Hyriins (H8) include an explanation of the fact that it functions completely. Ntrium hydride is only able to reduce the sugar acid electrons. 58) 2 ^ R2 ^ fl ^ Winus xyated some alkyl-substituted utyrlctne, which in turn were obtained by silver acid, which was converted into serious inic acid with chromic acid. This way allows a general transition from a Cgdic acid to a corresponding Cgdic acid to a Ctm poorer Cic acid. The disadvantage of this energetic abbreviation lies in the elimination of permanent substituents. 54) L. Fieser and W.H. Dut, J. Amer. Chem. Sc. 63, 782 (94) R. Fittig and 55) M. Ruhlmnn, Liebigs Ann. Chem. 22J5, 322 (884) R. Fittig and A. Wlf, ibi. 288, 76, 204 (895) F. W 56). Semmler, he. eutsch, hem. Ges. 39, 285 (906) 57). elleu.j. Amer. Chem. Sc. 5, 59 (953) 58) R.F. Nystrm, W.6. rwn, J. Amer. Chem. Sc. 70, 3739 (948) 58) H. L. Wlfrm and H .. W, J. Amer. Chem. S. 7j3, 2933 (95)

22 5 M Re et l. un trunk et l. describe a selective Oxytin er XLktne with rm in lkllshem Milieu (IT). If the rectin leads to a KetsSure, we of course assume that there is a Ï Substituent. The rectin takes place according to the following scheme: R RCHCHR R une »i J RCHCHCH2COOeNe ^ ü RCCHCHjCOOH (7) 0 CH r9 u 2 OH 0 V Z n 0 In the course of our work a very milky xytive ring opening with silver oxy was worked out. The silver oxide precipitated from alkali acted on the lacquer and in turn fell into metallic silver. The Methe lfiot can be compared with the Oxytin es Purfurls for renzschlelmsäure 6). When using energetic oxytine remedies such as Kliumper, chromic acid must always be considered to be able to produce catfish while taking into account the problem. ^ 3.3. With special RSJ & Snzle. All rectins, which can be exported with an ester group, can be transferred to the ylctne, ie the mn isylic ester. Hyrxmic acids derived from en YLktnen are ls Km 2) plexiblner for en qulittive proof, as shn in 59) J.A. M Re, E.H. Chrleswrth un D.S. Alexner, Cn. J. Reserch 2, (943) 60) R.R. Trunk and C.A. Tner Werf, J. Amer. Chem. S. 69, (947) 6) M. Delephine and P. n n e t, ull. S. chim. Frne [4] 5, 879 (909)

23 6 he discussed the properties of phenylhyrzine. Hyrzin are able to open a link ring with the help of a ÎfHyrxyhyrzis or Fhenylhyrzis. 65) For the synthesis of methynn s C (Aminbutyrlktn using ntrlummethylmerptl according to Flieninger are opened (8). CH3S N * CH2CH2 II> CH3SCH2CH? CHC00ONe O CHNH2 l (is) \ / NH2 II 0 on the elimination of the heat * Slzsure's Aethnl causes a transesterification of the Lktn, and a ring results in a chain structure (Hyrcyester) (9) .66 RCHCCCOOC2H5 (ig) OH The ring-opening rectins can be reduced by disappearing Jf Lktnbne at 5.6 i * in the IR spectrum you are well versed. 62) Cf. Kp ...), Re. Trv. Chim. Pyss 42, 30 (923) 64) E.E. Mikhlin and M.V. Rubtsv, l. bsc. Chim. 27, 69 (957) cited in Chem. Abstr. 5, 6463 f (957) 65) The CHAminbutyrlktn ought to be available from us. See to 43). E. H. Meinke and 66) S.U. c Elvin, J. Amer. Chem. P. 57, 443 (935)

24 7 HO CH 3 K.0. CH3.4. Ismerle er QLktne A rarer form of ismeria of a symmetrically substituted CC (tination can be obtained by ring closure As stated below for the 3rm2butnle, we em erythrhlhyrin s trnsoxy and us em threhlhyrin s isoxy. CH3 r CH3 H erythr trns HO H CH3 r CH3 CH3 thre eis Similarly, he Aitin vn Dibrmrben *) n eis, or . uf.69> Trnsuten2 Gemetrischismere Cyclpnerlvte It is essential to point out here that the formation of iserene is determined by the design of the initials. 67) H. 0. Huse, J. Amer. Chem. Sc. 77 ,, 5083 (955) 68) S. Tinsteln and H.J. Lucs, J. Amer. Che. Sc. 6., 576 (939)., T.c4h0 »»: HCr3 Cr2 69) P.S. S k e un A.T. Grner, J. Amer. Chem. Sc. 78, 3409, 5430 (956)

25 8 In a presentation of five, substituted two-fold elements, we encountered a similar ismerism, which we should now assume for ourselves. The general terms: RCH CH. HR «s r can be divided into two separate ismers: RR RH JcCi. un je C <_ H *! ^ H H <, ^ R 0 CH2 0 CH2 II II 0 0 eis trns A separation of these in the case of intimers into pure forms, we have not tried to avoid that our lines contain any suitable functional groups. One of the more suitable ingredients is hyroxycitrnenoic acid. Such a separation is carried out and we are able to clarify these theoretical questions with the help of magnetic nuclear research. Hit of this methe can be differentiated, for example, when test results in substituted licyclic rings are insistent. S 7) Lemteux and Hitrbeiter examined the institute in the next two hexacetyl sites (20). 70) C. Mrtius and E. H u e, Z. physil. Chem (94) C. Griebel, Z. Under Food 83, 482 (942) cf. to: O.Ashn, er.eutsch.ehem.ges. 27,200 (894) A. Werner, er.eutsh.ehem.ges. 2.3046 (899) p. Lemieux, R.K. Kullnig, 7) H.J. ernstein and W. G. Schneier J. Amer. Chem. P. 79_, 005 (957)

26 0.8 9 9.9 OAc .. OAc OAc) b) Between the two isms () and (h) in Frmel (20) there can be a clear distinction based on their NMR spectra. Noteworthy are the investigations by Freemn et l., 72) which coupling methods he determined vicinal un geminal profiles in his equation. The analysis of the spectra made it possible for the preferred artists. The ismery he synthesized ICTs, or the equivalent of the KMR spectra, is described in Chapter III .. it deals with the therapeutic part. 72). Freemn, K.A. M c Luchln, J.I. Musher and K.G.R. Pchler, Mlec. Physics [415, 32 (962) 73) We made the common coupling with c.p.s. and the opposite sign for the vicinle coupling.p.s. un 4.6 c.p.s. given.

27 20 II. Synthesis of a Lktns us en (is + trns) ßenzyllenbuttersfiuren (IV) As was mentioned in the introduction, he led the attempt to produce it 3MethylInphthls according to Dtt and 74) v l) gchi to a Lctn. The synthesis is given in the following rectin scheme: CH2COCH3 I CH * 3 ^ CH2ÇCH2COOC2H5 »^ CH = CCH2COOC2H5 OH I PH CH3 a j Lktn * ^> CH = CCH2COOH VA TV" The ability of phenylcetns (i) with mixed esters under refreshment conditions Proceeds in good yield. The hydroxy ester (II) is hydrolyzed with phphrxychlorine in pyrine and then saponified with a metallic solution to give acid (IV). The acid (IV) can be separated into insoluble separation by means of fractionated crystal Knfigurtin carried out by evaluating the physico-chemical measurements (UV, pk determination) and ismerization tests. Was:, 8. The ratio of the ice and the insisme 74) DK Dtt and P. ghi, Sei. N Cult. 8, 243, 525 (952) 75) "Refrmtzky Rectins", Orgnl Rectins ,,, Jhn Wiley, New Yrk, (942)

28 2 R / CH2COOH R CH3 H XCH3 H NCH2COOH> cisiva trnsiv The Ismeric refers to the mutual location of phenyl and xymethyl groups. Thanks to the "Llngrnge llyli" coupling, like thnery et l. It has been shown that both systems (ITA and IV) can be determined for the two possible configurations. Therefore, the recordings ONLY spectra confirm our efune. The cyclization of the acids (ITA and IV) in Flyphsphrs & u 77) 78) 79) re resulted in a terbinung with the composition CH2 2 * s * e has the typical absorption in the IR spectrum at a saturated YLktns at 5.6j *. The assumption that it is similar to s (i methyl-phenylbutyrlctn (TI), for CHCH, n 0 VI 85) would initially be disregarded by an independent synthesis and comparison of the I spectra. 76) A. A. thnery, C. NrClin and H. Günther, J. Amer. Chem. Sc. 84, 2748 (962) 77) R. N. ell, In. Closely. Chem. 39, 36 (947), ibi. 40, 464 (948) 78) J. K, J. Amer. Chem. Sc. 75, 89 (953) 79) F.D. Fpp un W .. Me E w n, Chem. E e Reviews 58, 32 (958)

29 ~ v! 22 r i IM. IMP ni Wttll II "m irrp i lir ii" il ipi ri ji [«ni« t 3 "V tti ri in inrrnr ITTr TTT iïn TT TT ii Uli ^ ^ ~ Ml ,. il Af JA l 3: f \ u / ~ fl L, L ^ i. ^ ~ Jill 3SS k * / ri: stf i A li I Tj \ i 44 TT pt II! Il f T II rl] il *. L. i,. * Li_ ri i ill, _l ^ = f A: IR spectrum es Lktns (VA) in CC4 3: IR spectrum es Lktns (VI) in CCl ^ Fig. Jhnsn and colleagues yllized y, 3fdiphenylvinylesslgsure (VII) in concentrated sulfuric acid at room temperature for! f, if diphenylbutyrl (VIII). Xc = CHCH2COOH VII RCCH, II 0 CH2 V g 0 VIII This system now represents a so-called end-to-end equilibrium r. The long implementation of our ice (IVA) and trns (IV) acids again led to Lktn (VA). Lktn ( VA) was not identical with (VI). When we examined the KLktn (VA) in more detail, it seemed important to us to secure the origins (IVA and IV). 80) WWSP Jhnsn, J Shneier ,, W. Petersen un J. Amer. Chem. Pp. 69, 74 (947)

30 23 II .. Slchrgtellun «! He institute in he starting points (IVA and IV) 8J (IVA) and (IV) were hydrolyzed with PlliumKhle in Aethnl. 82) / i In both cases, the liter would contain methylphenylbutyrate (IX). CH3 O "CH2CHCH2C00H Derbxylation es riumzes vn (IVA) and (IV) results in 60 dimethylstyrene (X) .83) 84) CH3 The acid could be converted into sisismers in 100% yield when irradiated with UV light Ismerization has now provided the right to agree on the legality of the institute vn (IVA) and (IV). 8) This work was carried out by Dr. OA Stmm, Teh.Chem. Lbrtrium er ETH, Zurih. 82) HE Crter, J. il . Chemistry (935) 83) The award prizes were awarded by Dr. H. sshr, CIA AG, sel. 84) A. Klges, er. Eutsch, hem. Ges. 37, 72 (904)

31 24 III. Synthetic clarification of the Lktns (VA) A. Chemical ways III .. Synthesis IIIiliii _ ^ = MethjlJ ^ = henylbut2rlktn_ ​​^ vi) As we can see from a flint, the synthesis is based on known methods, the preventive traditional Chenle unprecedented no difficulties. ^ COCH2CH3 ^> COÇHCH3 ^ COÇHCH3 r CHCOOC2H5 XI XII XIII COOC2H5 <^> CHCHCH3 «« ^ COCHCH3 ^ COÇHCH3 0 CH2 CH2COOH ÇHCOOH V COOH II 0 VI XV XIV is to stage he ß enzylbuttersure (XVr Hlgglnbth et l. worked. The lubrication of the test facility (XI) was carried out under extremely fine conditions. By means of a Khlenixystrmes, the solution was introduced into the cold ectinsis in a circular manner, in order to reduce the cytive influence of the hydrated fluid that was released, ie the solution with Khlenixy was coiled up to the negative effect. Water-efficient leakage 85) L. Higginbth, A. Lpwrth and C. Simpsn, J. Chen. S F. M y e r un G Stmm, er. eutsch, 86). former Ges. 56, 424 (923)

32 25 CHrmprplphenn (XII) was kneaded with Kllunläthylmlnt in the usual way at 80 C, and subsequent oil saponification led to prpiphenylmnic acid (XIV). The derbzylation results in the (5-enzylbutyric acid (XV), lower IR spectrum, C, H analysis and equivlent weight determination of the compounds in the compound (XV). The further task now is to reduce the jfket group in (XV) selectively 87) to the secondary alcohol. The complex metals are able to reduce the individual chromium functions extremely specifically and in good yield. The literature on the usability of these complex complexes is very extensive. It should be pointed out here only two large summarized statements 88) 89) * gen, such as in particular one work by H.C. rwn, eat closely with the development of chemistry, he complex metllhyrie is verbun. For the reactin of a ket group in addition to an ester functin, 9) Arbelt Greners is of special interest. Ntriumbrhyri proved its worth in our case, and the mineral acid used to destroy the excess Hyris led to the cylolysis of the Lktn (VI). Dsylktn (VI) has the typical Crbnylbne at 5.6m in the IR spectrum. The absence of an absorbency level at 6.05 6, u concludes that there is a double connection in ß, position u. This could result from the ring closure via the enlfrm (2) he-enzylbutyric acid. O CH3 c ch2ch; = î ^ c = cch2ch ^ c = cch3 OH 0 CH, xv V 2 l II 0 i J (2) 87) Cf. Kp) NG Gylr, Eeutin with Cmplex Metl Hyri es, Intersciene,) E Shenker, Angew. Chemie 73, 8 (96) 90) H.C. rwn un.s. SubbR.J. Amer. Chem. Sc. 78_, 2582 (956) 91) P.D. Grener, G.R. Hynes and R.L. rnn, J. Org. Chemistry 2_2, 206 (957)

33 26 In the section it was pointed out that the fretric acids tend to lead to negative effects on pyrolysis 47). The ingenuities of a milene pyrolysis are also beautifully given by the distiller. The unchanged acid can be separated from the neutral solution by shaking with icrbnt and isolated again from a distillery. With ß (pmethxy) benzyl ttmethylpropinic acid (LVIl) we could actually do this. We isolated sweet, X-unsaturated liquors from a distillation of fatty acid. As expected, this showed in the I spectrum in addition to the Lk tnbne at 5.6 (* and also the absorbency of phenyl-conjugated doublings at 6.05p *. The greater tendency towards enlization in the case of phethxyerivt compared to the acid (XV) could be attributed to the extended youth system (22) (22> Influences on structure and rectity that were established by Knjugtin er mesmerie were very broadly examined and interpreted. In the absence of a double bond, we tried, to be on the safe side, the increase in water with AmsKtlystr n at links (VA un VI), ie about negative. As was nicely indicated in Section II., The reactin product (VI) er p> enzylbutyric acid (XV) with an originally synthesized fluke (VA) is not identical. This statement is based on a difference IR spectra (see Chapter II.). It is noticeable that the individual levels of absorp- tion differ essentially only in terms of their intensities. 92) Cf. Chapter IV .. 93) E .. Gul, S Mechanism and Structure in er rgni sch Chemie, Verlg Chemie, Weinheim, 962, S) IR spectra see page 22

34 27 erb There was still the possibility of an intralmlecular rearrangement possibly taking place during the cyclization of the (i, îf unsaturated acids (IV »V)). The syntheses of three other works (positionalism) are described below If a phenyl methyl group could have arisen. IIIili2i_jJ> Methyl _ ^^ hen2lbut2 lktn_xxxil2 CH3CH (COC2H5) 2 COOC2H5 ^ COCH2CCOOC2H5 CH3 XVI XVII I XVIII ÇH3 ÇH3 ÇH3 COOCH3 I 0 XXI XIX. RCH3 COOCH3 I XXI 2 XIX Alkylation of the ulnester ji, 95 nn with phenylbrmi (XVII) 96 first with methylene dicrbic acid ethyl ester (XVIII). The saponification and decrbxylation led to (enzyltmetbylpropinsäure (XIX). The same compound was obtained from methylsuccinic acids 95) F. k, Lleblgs Ann. Chem (906) 96) A. Oppenheim, er. eutsch, chem. Ges. 34, 4227 (902)

35 28 hyri un enzl. The methyl ester (XX) was caused by the action of Dizmethn in b. Ether made. Ntrium brhyri was used for the selective reactin of JfKetesters (XX). The conversion of the 5Hyrxymethylester (XXI) to the CtMethyl Yphenylbutyrlktn (XXII) 97 first freezes the icical saponification of the ester group. The intermittently formed "Hyrxycrbnsäure in the presence of acid easily cycled to the Lktn (XXII). 0 CH7 OH V II 0 XXVII XXVI The ester (XXIV) formed by the acidic esterification of the levulinic acid (XXIII) ran into a compound (XXV) with phenylmgneslumbrmi, unclical saponification resulted in the relatively stable ^ Hyrxyphenylvle 97) 0. Mumm un K. rersen, er. Eutsch, hem. Ges. 5J5, 2295 (923) EE vn Tmelen 98) and S. Rsenberg ch, J. Amer. Chem. Sc. TJ_, 4683 (955) 99) A. . Grte, E. Kehrer and Tllens Lieblgs Ann. Chem (880)

36 29 ric acid (XXVI) .00) The ring closure (XXVI XXVII) is brought about by the action of a uric acid and a continuous distillate. The IR spectrum es} fmethyl îfphenylbutyrlktns (XXVII) 3200 shows the characteristic crystalline oscillation at 5.6 u. 00) J.J. Trivei and K.S. Nrgun, J. ünlv. nby [0] 3.99 (94). quoted in Chem. Abstr. 36, 3802 (942)

37 ~ ÇH3 30 This connection is unknown in the liter. Therefore a new synthetic route had to be worked out and two independent syntheses carried out. weren. The synthesis was A O ^ C0CH3 XVIII CH, 0 XXIX CH3 NVCHCH0 XXX for \ icn CH2COOC2H5 CH; ^ CHCN CH3 = ^> CHCH N0H XXXIII XXXII XXXI \ _7CCH2NHC0CH3 i H2COOC2H5 XXXIV NO ^ CCH2NCOCH3 CHC00CH XXXV ^ CH3 ^ CCH2OCOCH3 CH2COOC2H5 XXXVI i CH3 OffH2 V "2 0) it is essential to combine synthesis, which means Kyrlversh2 V" 2) Myrple XXXVins On the other hand, the IR spectra always showed that the Alehy group did not adhere to the clichéd attitudes of Knenstin.

38 3 The Glyciesterknenstin es Aetphenns (XXVIII) after Drzens and the subsequent splitting of the Ester (XXIX) to the Hyrtrplehy (XXX) were carried out according to the regulations of the Orgnic Synthesis (XXX). The coating of Alehys in s nitrile takes place in a well-known manner via s oxime (XXXI) and subsequent watering with acetic acid nhyri.In order to avoid saponification of the oil, the acetic acid formed is removed from the rectin mixture by distilling. The work of Newmn and Clssn has proved to be well reproducible. A knight in it Hyrtrpnltril (XXXII) with poor sigest, the information of Ws and employees was misfied. The authors made use of this ether in the presence of nitrium and achieved yields of around 20%. Our mifiktin bestn rin, that the reactive intermediate stage it Nltrlls (XXXII) was produced in this part (23). ÇH3 ÇH3 CH3 G CN fccj e HNHj ^ ÇjCsN (23) XXXII XXXII Now the resulting intermediate (XXXII) was mixed with an ester of a size at 70 C. The Tleftemperturmethe resulted in yields around%. 02) U .. Drzens, Cr. heb. Sences Ac. Sl (904), ibi. 96, 884 (932) W.S. Jhnsn and J.S. elew, L.J. C h n n un H.H. H u n t, J. Amer. Chem. P. 75, 4995 (953) 03) C.F.H. Allen and J. Vn Alln, Orgnic Synthesis 24, 82, 87 (944), Cll. Vl. HI, 727, 733 (955) 04) M.S. Newmn and d. Clssn, J. Amer. Chem. Sc. 66, 553 (944) cf. on H ". Tiffenu, Ann. Chlm. 0, 322 (907) 05) GF Ws, TL Heylng, ~ EH Schwrtzmn, SM Grenell, WF Gsser, EW Rwe and NC gn, J. Org. Chemistry 9, 290 (954)

39 32 Instead of it, Kliumtert.butylt was also used extensively. This provided a lower yield (33%). The selective conversion of the nitrile group in connection (XXXIII) initially appeared problematic. All metal hybrids are known to attack the ester group. At first, the catalytic hydrogenation appeared to us to be the most favorable method. It is possible to add the internal stage "b" that arises during the reuctin and to convert an alehy obtained by mile hyrolysis into the desired alkylene group with nitrium brothyri. Plieninger, 06 Wnzlick, 07 and Kuhn08 describe that the ctlytic hydrogenation of a nitrogen in the presence of ale provides hyregents, such as semicrbzlHyrchlri er Dinillnäthn (XXXVIII), in good yield via s formed imine al ehyerivte. Dinllinthn (XXXVIII) 07 forms a substituted tetrhyrimizl (XXXIX) with imines, s when shaken with dilute hydrochloric acid in the cold sfrts in s dinllinäthnihyrchlri un en alehy. RCH = NH "2L (CHW <3) 2» RCjf ^ Tft XXXVIII RCHO (CHNhO), 2 HCl \ s * H XXXIX In our case it is not possible to get to the alehy level with this method. It is necessary to take it vluminous groups 06) H. Plieninger and Kiefer, er. eutsch, formerly Ges. 90, 67 (957) H. Plieninger and G. Werst, er.eutsch, former Ges. 8, 956 (955) 07) HW Wnzlick and W. Löche, er. Eutsch, formerly Ges. 6, 463 (953) HW, Wnzlick, Angew. Chm. 74, 29 (962) 08) R. Kuhn and W. Kirschenlhr, Lieblgs Ann. Chem . 600, 5 (956)

40 33 us our tertiary nitrile (XXXIII) are literally used for failure. Finally, the ktlytische hydrolysis of nitrile (XXXIII) in the presence of acetic acid and platinum xylsylsylstryl led to the desired conversion. The obtained alkyl cetml (XXXIV) now represents a group r, which can be seized selectively. The X-acetylmine (imethyl-phenylbutyric acid ethyl ester (XXXIV) was obtained as a high-quality oil. The separation of the hydrogenation mixture is only possible by means of a neutral oxide of activity level II / II. With enzl / petroleum ether in the ratio: Compound (XXXIV) reim elulert wer en. The IR spectrum of the product (XXXIV) showed the absorption levels at 2.90 and 2.98 (fr for NH, at 5.93 IIA. For the acid emi un at 5.79 u, for The ester grouping. The nitration of the alkyl cetamine group in (XXXIV) was given by White in a mixture of acetic acid and acetic acid at 0 C with a very large excess of N trium nitrite. The latter can be converted to acetyl acid in a small amount in the kitchen while splitting off muscular nitrogen. 09) In an attempt to separate the hybrids by distilling, the compound (XXXIV) decomposed. The preparation of a sample for analysis could only be possible After high vacuum distillation in the cup, the artisan surface flies directly to the hot oil surface. S wure he mean free path cumulatively exceeded. 0) E.H. White, J. Amer. Chem. Sc. 76: 4497 ​​(954), Ibi. 77_, 6008, 60, 604 (955)) T. Fujii, M. Tshlr, K. Ohr and M. K u m, Chem. Phrm. ull. (Jpn) 8_, 266 (i960) (English.)

41 34 NO RNHCOCH3 R (VC0CH3> [RN = NOCOCH3] XXXIV XXXV XXXV (24) R = ^ HCH3) C (CH2COOC2H5) CH2 ROCOCH3 + N2 I XXXVI White describes ß ie aylwnerung and splitting it dizetts (XXXV) always »XXXVItung We accompany the formation of olefins. The mechanism is as pstulated (25): RCH2CH2N = N0COCH3 »RCHjCH2 * + N2 + OCOCH3 (25) H RCH = CH2 RCH2CH2OCOCH3 As Huisgen 2) and colleagues could show, this is in line with a heterlytic Chrkter er rectin. A comprehensive discussion about the decomposition of intermittently occurring liphtic dizesters can be found in the 3 also by Zllinger. In order to obtain an olefin according to (25), a hydrogen in ß-position to the diz group must have a hydrogen-lumine. This does not apply to our case (XXXV). Instead of olefin formation, we can use a Wgner sea catfish enclosure in a 50% yield according to the following scheme: 2) R. Huisgen un. Reimllnger, Lieblgs Ann. Chem. 599, 83 (956) R. Huisgen and C. Chem. 60,, 2 (956) RUchrt, Lieblgs Ann. 3) Hch. Zllinger, Dlz n Az Chemistry, Aliphti n Armtic Cmpuns, Intersciene, New Yrk, 96, p.20

42 35 ^ CH3> ÇCH2 «CH2COOC2H5J / \" I CH3CCH2 CH2COOC2H5 CH3Ç ^ 0 CH2COOC2H5 XXXV b XXXVc i XXXV CHCCH ^^ CH2COOCH XXXV e fast as an intermediate product during the synthesis of the 2fLk tns (VA) vr (III). Chrkterization resulted in a change, with the mixed melting point obtained SSure Kit (IVA) and the equality of the IR spectra no doubt about the identity of the two products (XXXV III ) un = it was allowed to persist. = The conversion of the compound (XXXVl) in s ßMethyl /? phenylbutyrlktn (XXXVII) carried out smoothly traditional saponification and production of the rectin product. 4) S. Wlnstein, ull Frnce 8_, 55 (95) A. Streitwieser, Chem. Reviews j> 6, 57 (956) w. Lwwski, Angew. Chemie 70, 483 (958)

43 36 MUVENUMTC * CH WAVELENGTH IRSpektrum es P> Methylftphenylbutyrlktns In CCI. Flg. 2 The IR spectrum shows how the authoritarian level is at 5.6 »», is moreover different from both tract spectra (VA) and (VI) (cf. Chapter II.). Synthesis CH3CN NC ^ P \. NCv ^ SCN COCH3 <^ C = CCOOC2H5 »J_ J H XXVIII XL XLI J <^ CCH2 AgOOCCH2C CH2COOAg

44 37 The production of fimethyl / iphenyiglutric acid (XLII) was carried out according to the regulations of Orgnic Synthesis. Acetphenn (XXVIII) was kneaded with Cynessigeter with the addition of Ammnlumcett. The oil, Çf> Dicyn / îmethyl / 3phenylglutrlmlml (XLI) arises from the art of esters (XL) with cynetmi. The saponification XLI XLII freezes energetic reactions, namely 3 days reflux with a mixture of sulfuric acid / acetic acid. A number of experimental difficulties were found in a Methe vn Winus to the Abbu er silver salts from glutinic acid derivatives. Only an extremely well-dehydrated silver drink could be successfully implemented. The fine blending of J and silver also plays an essential role. The powder rectin is extremely extreme and can be tempered by adding Sn. There is no possibility for ismeres to be formed on the basis of symmetrical us dicric acid (XLII). Anhyris, as a minor rectifier in the silver bullet, fears that it would form the base acid when it was shaken out with water. The oily ß-methyl [5-phenylbutyrlctn (XXXVII) acid was cleaned over s riuml and unsealed distiller under HV. Syntheses A and lead to an identical VLktn (XXXVII), sweet food structure can be explained with certainty. The synthesized ylctnes (XXII), (XXVII) and (XXVII) all have an IR spectrum which differs from that of Lctns (VA). Intrmlecular redistribution during the cycle (IV »V) is ruled out. We had no choice but to clarify this through Abbu ie Artitin es ÎTLktns (VA) b. 5) S. M, M E v n un D.H. Clemens, Orgnic Synthesis 39, 25, 52, 54 (959)

45 5 38 III.2. Abbu un Rlngffnung er ylktne (VA) un (VI) First, tflktne (VA) un (VI) were reduced with Llthiumluminiumhyri in ether. In both cases we got, 4dile. The rectin bluff could be removed from the IR spectra by the disappearance of the level at 5.6 and the appearance of the dissected hyroxyl level at 3.05%. A slight difference between these two IR spectra could not be explained unequivocally. At this point it must be noted that the poor resolution of the spectra does not allow any conclusions to be drawn about the structure. The CHanalysis (CiiHi6 2) un 8r xytive Abbu beier JfLktne (VA un VI) provided us with points of reference which allow us to ascribe the following structure to the reactin products: OH XLIV 2-methyllphenylbutnill, 4 (XLIV) was urh tsylation and subsequent distillation 3Methyl2phenyltetrhyrfurn (XLV) 6 transferred. CH3CH CH2 I I 0CVCH2 XLV The tsylation of Dils (XLIV) made it difficult, under certain circumstances (0 C TsCl / Py er at 5 C TsCl / enzl 248 hours) s Dil was not attacked. Energetic conversion (pyrine, 2 hours m reflux) led directly to the ether (XLV). 6) This connection was first made by Dr. O.A. Stmm, Org.techn.lbrtrium ETH, Zurich, synthesized.

46 39 It is to be assumed that only a mntsylt is formed and that splitting it brings about sylt formed chromium in an intrmlecular ring closure. The hyrlysis of a ditsylt would have to return the starting point. For comparison, we synthesized by the same route s Dil (XLVIIl) es ß Methylfiphenylbutyrlktns (XXXVII): mçcn CH2COOC2H5 ^ JjMpCOOH CH2COOH ^ CCOOCH3 CH2COOCH3 XXXIII XIII XI XLVII CH2XYLMUTIC acid XLVI XLVII-Phenyl-methyl acid XLVI-XLVII The esterification resulted in a large excess of n Dizme 7) thn. C, Hanalysis The IRAbsrptin (Crbnylbne at 5.85 (kv) and confirmed the correctness of the structure of the ester (XLVII). The reactin of (XLVII) with lithium aluminum thyri resulted in 2Methyl2phenylbutnili, 4 (XLVIIl). The IRSpectrum es Dlls ) It is not identical with one of the reuk tinspruktes (XLIV) at the links (VA and VI). The xytlve figure X "Lktns (VA) finally tied the links. First we would have carried out the oxytin with chromic acid, ie jech too far-reaching figure 7) A, I, Y 0 ge A, Textk f Prcticl Orgnic Chemistry, Lngmns 96, p.970

47 40 HS) Mleküls (VA) led. Enzoic acid is isolated as the product, ie identified by the mixed melting point and a comparison of the IR spectra. In chapter 2.3. A mile xytive ring opening was briefly described with silver xy. This Abbu was now delivered in a final version in the XLktn (VA). for the position of the substituents. An icical solution of hyroxycrxylts of (VA) was mixed with an icy-aqueous solution of silver nitride. The work-up is carried out using a non-stirred suspension. In the iconic extract, enzylbutyric acid (XV). We can then formulate the rectin bluff as follows: ? ^ HCH2COOeN 22S ^ CCHCH2C00H H * h ô VA XV This statement is surprising for us; If this means that ß (VA) and (VI), s "unknown" JfLktn and re uktinsprukt he ß-enzylbutyric acid (XV) must be synthetic. The position of the methyl and phenyl group in the Lktnring (VA) is determined as one. 8) The use of Kliumpermngnt also resulted in Abbu es Jf Lktns (VA) up to enzic acid.

48 9.5 4. Spectral scopes The previous investigations showed us that the two compounds (VA) and (VI) 9 are similar, ie when they are in the ß position a methyl group and a phenyl group do not carry positionalism sin. The UV spectra naturally show no difference (> = 208 »(Enbsrptin); = 200 for (VA) and mux * I >> 208 lit (Enbsrptin); t = 3800 for (VI)). mx. i list for the interpreters of the NMR spectra at links. In both tests it is similar to a mixture of two compounds, which are present in a different relationship. On the basis of an xytlven figure, the two connections must have the same sequence of breaths via the same structure; they can only differ in their stereochemistry. The strong doublet at 9.3 t in spectrum C is attributed to the methyl group. The general shift of the sign to a higher field is due to the steric stabilization of the free rotation of the phenyl and methyl group in the knot belts of the two functions. One ls durh the methyl group over a phenyl ring to lie. The methyl particles are shielded by a stream of magnesium induced in the phenyl nucleus, which shifts their signals to a higher level. The same group is found, only in this case much weaker, also in the spectrum T, it must also be present in the case of the reuk tine product (i enzylbutyric acid (XV) at a 2) low percentage. 9) The two indices A and to mark the links were introduced from the beginning to indicate the institutional identity. 20) The NMR spectra were given by Dr. f. v. Philiphrn, Orgnischchemisches Institut der Universität Zürich, on a Vrin A 60 device. 2) Cf. to Kp..4.

49 42 NMSpectru es tf Lktns (VA) lt TMS ls internal reference source in CCl ^ (c) KMSpectru es 0 Lktns (VI) with TMS ls internal reference source In CC4 (T)

50 0.5 8, t 43 0.5 «* 8.9 The only weakly predicted signal at 8.8 t in spectrum C also p> belongs to the methyl group, so here there is only one frequency, so it is no longer one steric interaction with a phenyl nucleus. This is only possible if two groups have been advised to separate. These next, correspondingly different types of it are attributed to methyl / phenylbutyrlctns. Let us assume that 0 <, fj in the line. And prtnen // ^ cchp IIH * 0 CC VH * »0 The signals at 4.45t correspond. An 4.55% methyl prtnen in er ls or trnsfrm, at 5, X and 5.25% en H in er ls or trnsfrm, while the km plexene group at 7.0 ie ß un ie two & prtnen A fine structure analysis of the spectra is currently in progress. From what has been said so far, it can be seen that in the case of supposedly different lines there are mixtures of oil elements, in case of (VA) the cisknfigurtin, bel (VI) the trnsknflgurtln it (i methyl phenylbutyrlktns predominate you can try to interpret the differences between the IR 22) spectra (Fig.), on which basis we originally concluded that there are different lines. 5 f * un at 5.5 V vneinner b. I 23) After liter turns were = CH daily oscillations a significant at 7.5 8tv Un 9.5 found. This is he e 22) The IR spectra see I Kp. II. It theretic part. 23) L.J. ellmy, ÜltrrtSpektren un hemishe Knstitutin, Verlg D. Steinkpff Drmstt, 37 (955)