DE1908274A1 - Separation and conversion of isomeric cyclohexane derivatives - Google Patents

Description

DR. F. ZUMSTEIN - DR. E. ASSMANN DR. R. KOENIQSBERQER - DIPL.-PHYS. R. HOLZBAUER

TELEPHONE 2234 76 and 221911

TELEGRAMS ZUMPAT CHECK ACCOUNT MDNCHEN 91139

BANK ACCOUNT: BANK H. HOUSES

8 MUNICH 2,

BRÄUHAUSSTRASSE 4 / ΠΙ

52 / zö
Case 180
15.87-478

R. J "Reynolds Tobacco Company, Winaton" Salem, IS ₀ J. ₉ UoSeA

Separation and conversion of isomeric Cyclohexsnd © ri ¥ a, tCTu

The invention relates to Ves ^ esserunges, "in & ®r Xr Xr separation of 1,4-Dialcyl-1,2-epo2ycyelohexanlsoHi © reii, and iron allcenyl-1 _S 2» epo2ycyclohe3 £ anieoffisr © 2i and the separated isomers in choiaiselie Verbinäungent) the are useful for the synthesis of menthol

It is known that various © substituted with a single cyclic double bond among organic peroxy acids such as pereseetic acid, perpropion- = · acid or m-chloroperbenzoic acid epozydiert to monoepoxyderi can be. Particular examples of such substituted cyclohexenes are 1,4-dialkyl-substituted 1-cyclohexenes and i-alkyl-4-eyelohexene, include such compounds various important terpenes, such as 1-Henthen, 3-Men then and limes. The epoxidation of these cyclohexenes with an organic peroxy acid leads to the formation of practically equal amounts (i.e. a 1: 1 ratio) of the corresponding eis and trane epoxy isomers. Trans-1-menthenepoxide and trans-limonene-1> 2-epoxide are particularly desirable because they are stereoselectively converted into 2 "menthen-1-ol or 2,8-p" Menthadien-1-ol can be converted, both are wich · =

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Common intermediates for the synthesis of menthol. The conversion of acetic acid with trane-1-menthenepoxide leads to the formation of i-hydroxyneocar-vomenthylacetate, which, as is known, can be pyrolyzed to form trans-2-menthen-i-ol. The conversion of acetic acid also leads to trans -Llaonen-1,2-epoxide for the formation of I-hydroxyneodihydrocarvyl acetate »which, as is known, can be pyrolyzed to form trana-2,8-p-menthadlen-1-ol cie-1-menthenepoxide or cis-limonene-1,2-epoxide for the formation of 1-acetoxyneocar-toaenthol baw. I-acetoxyneodylhydrocarveol, neither of which can be converted into 1-menthen-i-ol by pyrolysis, as in the case of the trans-poxyomers.

It has been found that oia-1-menthen-1-ol and cis-1-menthen-1-ol can be used to produce trans-2 "* menthen-1-ol and trans-2,8-p-menthen-1-ol, albeit an additional one Chemieehe implementation is required in every case. Ee also became a suitable method for separating mixtures of cis and trans isomers of 1,4-dialkyl-1 <-cyclohexenes or i-alkyl-i-alkenyl-t-cyclohexenes, including terpenes such as henthen and limonene Mixtures of the cis and trans isoaers, found "On this basis, for example, a suitable process for the production of 2" menthen-1-ol and trana "2,8-p-menthadien-1-ol was developed, whereby one von HiBchungen auu eis- and trans-Ioomeron starts from Menthen-1,2-eposyd bsw, Limonen «-1,2-epoxy and whereby one makes use of both the cia- and the dsn trana-Ioomer.

The present invention is based on the finding that Mixtures of ci- and trans-isomers of 1,4-dialkyl-1,2-epoxycyclohexanes and cia- and tear-i-alkyl-i-alkenyl ^ i, 2 = epoxycyclohexanes can be selectively treated with water = - nen so that the cAs xsomer untex · formation of a traije ~ 1,2 ~

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Dio3.ee reacts and the trana-1 ₀ 2 ^ Epo ^ disomer @ -fen remains ο The resulting hiacbimg from "trans-Epoayd and 1,2-diol can easily be separated from simple lay methods this 1p2-diols, in general, relatively insoluble can therefore in Waeeer and due to the Löslichkeiteunterechiede be separated easily and conveniently. the invention is based Aich wel "continue to impact the observation that the just-mentioned trans" = x 1, 2-Diolo (more precisely _r told 1 "4-dialkyl-trane" 1 ₉ 2-dihydr®sy "= · cyclohexane and 1" Alleyl "-4-" alken5 ^r l-transr1 "2-dihydr © 3E2f © yolo" - kexane) olective in the 2 " Position can be esterified, and the esters formed can then be simply pyrolysed in bo valuable end products such as trans-2 "MoBthc2i-1-ol and 2 _f 8-p-MoBtkadiGn <" 1 ~ © l can be transferred to "

The object of the invention is therefore the creation of a process for the formation of a mixture of them and tear "** Xsomers of 1,4" alkyl-1,2-epozycyclohexanes or of iA ^ Jcyl- ^ alkenyl ^ i ^ - epoacycycloheicenen and especially such Yerbindungen of the TerpeJixeihSp characterized © = g _s jrennseiclmot .is that the mixture is treated with water, wherein daa ci.fs-Ißomore in CLAA according © 1,2-diol umgev / andolt v / ill, v. ^r While the traas-IßOBiere remains unaggregated, and then the tranc-Isoaisre yqxl is separated from the 1 _w 2 "= - Biol.

Moreover, the present Brfindung manages ela ancestors, in which a trans-1 ₁ 4-dialkyl-1,2-diliydroxycyclobsxan and particularly to such a compound of Serpenreih © ee "= is esterified tively, ujn to form a 2 ** KonoeBter which the _p is then subjected to pyrolysis «,

According to a particularly valuable object of the present invention, a mixture of ice cream and traa

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1 "Menthen-» 1 _p 2 "öpoxydisomeren or separately a mixture of ice" and trans-limonene-i ^ -epoxydisomeren method according to the above separation "according to the invention is the resulting trans-diol _$ derived from the CIE-isomers, esterified selectively in the 2-position and the resulting Estonian? to trans "* 2-i! enthen ~ 1 <=" ol or trans "2,8-p-menthadiene pyroly" slert "Furthermore, according to the invention, the unchanged trans-epoxides can be converted into trans" 2 "menthen" 1-ol or "trans «-2,8« p-Hen ~ thadien-1-ol can be converted in the usual way, 2 »B ₀ by reaction with acetic acid and subsequent pyrolysis of the hydroxy acid formed» The two products according to the invention are valuable intermediates for the synthesis of menthol _β

Xn the following description is the implementation of the ciss-Epoxyißomaren with water to form the corresponding trane-1,2-diol in the separation process according to the invention For the sake of simplicity, given the term "hydration".

The separation process comprising the hydration of CI8 "Epo2ydes while leaving the trans Dpoxyd unchanged, due to the greater responsiveness of the cie Zsomeren with water, the Reaktißnsbedingungen must therefore, for _o Bo be" züglich time, temperature, pH, etc _a , be chosen so that the desired selective conversion is achieved. Selective reactions are of course well known in chemistry and, as usual, simple preliminary experiments enable the required reaction conditions to be determined in any given case.

The treatment of the epoxy isomer mixture with water can be carried out under acidic, alkaline or neutral conditions.

If acidic conditions are used, hydrogen chloride

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acid, Sohwefelaäure, perchloric acid, formic acid and acetic acid are used, for example _a acids preference be white used in veMiüLantem state and iia general call Säurakönzantrationen O _C OO1 ^e /> to 15 "0 volume ^ applied _f na a whizzing pH sswiechen 1 and 7 to obtain "Te nvendung hohon excessively from Säuran ₀ especially in higher Konzen" · over longer © äeiträusa and / or Lei 2 © mperature © n must be veriaieden ₉ to hydration to haiten he desired trane-Epo ^ äieomeren minimal, and also to Pinalcomyalagenmg of the epoxides or entetandezien glycols to ketoprodulcts to venaeiden »The temperature, dia -ras- the opening of the t3? A; as« »Epo35ydea in aqueous acid» isischusgoa. angawsndot wi2.'d _t is generally in the range from O ⁰ to 65 ⁰ C _s JThe mixture of the? Is isomeric epoxy with diluted Säur® a while stirred _t enough atieleren hyör-order the CISS Epozyiaoiaera to and Transs "" EPO3 £ yieo * "mere pralctiseh miverän <s3? T zux1ic] rzulass © n _e This is in all = · Mean in about 5 minutes "to 8 ₉ 0 hours reached»

2) The selective hydration of the cis ~ epxyde of cis- / trans ~ 1 _p 4-dial: yl ^ 1lg2 «Qposycyclohesang0miBchen odor of cio-Ztrans

^^ epoa ^ cyclohexangoaiechen, so öaß di ©

praJftiaoh changed

can also be used on wlrlceaxae white mil ar use of alone ₀ ScB «Lsltungswass®! · or distilled ¥ aeeer _p

The at this © r-finäuagßgeiiiäöon Aua

iührungsiorm varf-zandet © Sempesatur la is generally in the range of AÖ ° to 150 ° C vorzugaweise _p in the range between 75 and 120 Oe ⁰ -The selective hydration under Tex * wend 'iig of water in Abwesoiiheit of acids or bases, in the eye " mine reached in 10 minutes to 48 hours «

The selective hydration of the cis-Epoaqrdes ran cis- ° / trane "1 _t 4." Dialkyl "1 _> 2" = "epoiycyclohexaag © mi8chen or des

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Mixing of cle- / trane "" 1 "alkyl" = "4-alkeayl-1 _p 2" -epoaycycloli © ian, so that the iran-epoxy isomers remain practically unchanged, can also be permeated under alkaline conditions, whereby BB aqueous sodium carbonate, Aqueous potassium hydroxide, aqueous sodium hydroxide or other aqueous alkali metal hydroxides in concentration ranges from, preferably at an alkaline pH between / and 12. They OF INVENTION in this & ungegemaßen Aueftihrungsform temperature employed is generally ia range of 70 to 150 ⁰ C and dae process is preferably carried out above 95 ⁰ G. The eelsktlv © hydration using alkaiiechaj? Conditions is considerably slower than when using water or aqueous acid, and reaction times of 14 days may be necessary.

Through the hydration of the cooking, di © cia-, and tane ~ leomers of 1,4-dialkyl-1,2 "opo3i ^ cyclohQ3anes or 1 ^ alkyl = - + - =" alkenyl ~ 1 _f 2- = > epo3cycycloh®2 £ a3) e: contains a, according to the He-making, "the cio-Isomorenp v ia above already running _s transferred ₀ ia the corresponding 1,2-diol These diols werdfm easily with physical cathode _s wio through? _{Filtration 9} Distilling under reduced pressure or by Ghroma.t?> ™ graphic Velchea pral "separated from trane-Isoiaeren: table remains unchanged

The Trane-1 _t-4 DialJcyl "1,2-epoxycyclohexaae can with lower carboxylic acids, in particular Alkaacarboneäuren as Easigeäure or formic, _s ^ are esetst to a 1» Hydroxycarboxylatoster form. For example, according to the invention, a mixture of cis and trans-i-menthenepoxylsonerene can be selectively hydrated so that the cis * = isomer is converted to 1 ”hydroxyneocarvomethol. The trans-i-lißnthenepöacyieoaere wii? D in practically pure form

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i3Lttilökgewoan "n, this Transs-JEpoxyisoaere can then be reacted with a carboxylic acid (cf. · Example 19) ₉ such as acetic acid _v uage be constitutes" a petitioner, such as I ^ Hyarosgrneocarvomenthyl · = "acetja form to" obtained by pyrolysis in tranB " * 2-Hentken "1" oil can be converted " It conversion by pyrolysis of I-Hydroxyneocarvoiaenthylecetat to trans-2" -Menthen-1 "=> ol is for example from EE * Royals and J _4. Leffingwell in Journal of Organic Ohemisstry , £ 1 ^ 1937 (1966) * Paa through hydration deo cis «-1« = Menthen®poxyde8 ge «" formed I ^ iiydrcxyneocarvomenthol ksjcm ösn ». on a 1 "hydroxyneocarvino-methyl carboxylate ester" in the usual way, e.g. by setting with an alcoholic agent (see Example 20), v / ie an acyl halide, such as acetyl chloride, propionyl chloride, Benzoyl chloride or a carbonic acid anhydride, such as saoigeic anhydride, propionic anhydride and the like At the HarBtsllunf; the i-

estej? should ! HSR, \ s1q known, proceed carefully to remove oil © Horeteiluug Qi & ea Mr-noeaters eiehßrsustollen «Eia molane © equivalent or θ5.η small excess {<10 ^) of the acetylation agent is rorzugoifeiee and prolonged heating sen dei? 1'-Hydroj; 7aeocarvomenthy3iaoA! IoeatGre iia ÄKwesejßb. ^. I of acid © becomes v & X '& isdanp inter alia the formation of Diesterii and Xetoproduktsn

Similarly, a Miochung of CIA and spoxydisonaron by selectively © hydration of the su ~ 1 _f HyärGsyneGdihydroearveol give the trana Epoxyiöoaifiren in substantially pure JOM ₉ monen isolated * = 1, 2 = opozyd characterizing öaioa by treatment with a bonaäure, inabeoonaere a Hiedrigalkancarbonoäure ₉ how

in sicf-n i-HydroDEyneodihya ülDsrfütet would _e at ö <? 3? Py ^ ojc ^ ee

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Kenthadien-i-ol yields. The conversion of 1 a2 «epoxyd au trana-2,8-p ~ menthadiene« »1 ~ ol via 1« Hydro3cy «needihydrocarvylacstat was by EE ₀ Eoyals and J ₉ O. Lei« fingvell 4a Jouxmal of Organic Chemistry, ^ f ^ 1937 (1966). Bas I-Hydroai ^ eodihyärocarveol formed by selective® hydration of cia-1-lOfenthenepoxycl can to a I ^ Kydro ^ needihydrocaxuylcarboxylateä. * On UbIi = eh® ¥ eic® esterified ν © χΗΐ <& η _? z, B »by iaaetzu & g with an acetic acid halide or carboxylic acid anhydride as acylic anhydride (see * Example 22), like acetyl chloride _s Propio» j BaiiKöyiclilorid, acetic acid anhydride ,, propionsäu «·

and the like * Dies®% dro3Eyestö3? Saan can be used around 2 ₉ 8 · = »ρ« Ιί © ηϋΐδο1 @ η «» Ί-ο1 by ^ rrolße (cf. at «= · oplsi 25) h.Q3?suetull@2i _e Hocluoialßj bsi the formation of the 1-

should biaa as known _t

vosg € hc3ip w & to ensure the formation of a Monoeestra «

It is @ elbstv®3? Etändlichp that bsi the ^ lying 33ye ^ iafiuag optically active © products © saaltsa d © n ₉ wesa. man voa © ptiseh active £ ^ 02grdg © misch © 2i aas geht νωή racamiseh © Psödukto received wesd © n _e wetax mea from mischen Epo ^ dgeiai @ ch © si auis geht * S © result a _a B _ö M © ath © aöposyd® äas tsfaBfit ^ uiposyieoBidse voa C + ^ I ^ © posyd and {«)» »1« S! © ntli®n © po3 £ yde result in ßas C ^) <°

Baiapiele explain the invention without any explanation. In these examples, all temperatures are given in ⁰ C. In Examples 1 to 9, the mixture of cis ^ trans-epoxy isomers was obtained by means of epoxidation of (+) ~ 1 -Menthö "obtained by known methods, and the Hiachung had the following characteristics etikag [a] | ⁵ "+ 47.4 °, n | ³ β 1.4478, 53 # cia-Bpo3yd _s

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- 9 4? $ tsaaa-Eprayaj, boiling point 54 Ms 70 ° / 2 am «

10Og one? I ^ I'l & athenepozyd & tecbuBg vnu? D © & u & tea?

Guided tour for 24 hours up to 15Me 20 ° ait 490 a

das 5 föopfcm 3fo3L'cJiloz? säU £ · © e & tMelt (pH äar solution

ausfiel 9 wasd © äii ^ ch Filtration g®vf © ^ iea and XiüLiih ü &'üi Sscckuisa an ä © s X & fto Bas IFiXtsat u? ju? ä. © ®i% ξ, © stE-ab, I © 5? t, us 44-s 8 g of a Matoxlales zn ßas vorv / Äegoad i-'Hs & thnaöpöiiyö * mr _o Poiinigimg üIgbb®

Si © fl © pU2jl £ t 76 Ms 85 ^ß / 10 SSa ₅ , a ^ e 1 _ρ 448β ₀ [sfj ^ j en -f-54 _s 59 ο liie analysis ä®a IMR ^ Spekt ^ uias #i nonen BBcmrstes K9lgte _s that

Example 2

4 Stopper ^ © zreklorßäus? ® fpH ä @ x ^D SSsiiag as 4 _S 5) eathi © lt ₈ β SeiaaneAi laag Issi 40 ^ö firmly gegtliEt «Sa

das © -as € @ 2? Mige & img

aa ie ^ 3ia £ t C ^ P «» @ 2 Ms 84 °) - Bin®

even »" bsi 86 bit 87 ⁰ ? md feaeaB eia © «ptiseke

Rotation ¥ oa [®3§ ^s · 5-43ί2 ° «The filtrate waxes with

extracted imä © g> gave 14.5 g of a ifeiterlal © s _$ <äa, s ®atlii @ lt _o Das Xetstgeaaaat®

cleaned « AmbXjb® des Ep © zyd © 3 aaigt ©» äaS rlis Profes 190 ^ ig @ s

009831/1885

ίο

Balepi oil 3

50 g of eiiioo i ^ ilönthenepoxydgeiaisciiQfj mid 20Q ml of water, containing 3 drops of PerchXorniiure (pH öyj? Lciaung »4 ·» 5) were 10 minutes, lan * ?; 1 »Hydroxyneocar · - vigorously conducted at 60 °

O, fell l> aln cooling aiiß öox · Misfclmnß and was collected by filtration SSEI? _T omvm it VOG 17.7 g (mp <> β 83 "to 84 ° C) * A-urak vietallieiertö" Prcolie (i'cb & iilspunljrt 86 " up to 87 °)

p to ο ine optical * D ?. ^e oUun-i from [«] p« + 45 * 2 °

nan Das Piltrat vmrdo nit Ikc.ion extreh5.ort, wobe.i / 27 _y 4- g of a material ßC) wnnn _t ßaa -'roivloßflncl 1 ~ iteai; hcm «? Ti0xyß represented IJao Epoaq-d ^ snutrde £, nfjchx. Ot-: - atO53. * A.phiHc} i {jero.inigto analysis deß in-IH «Speki louas the ßoreinißton l ³ rol> e showed _f that it 1öO? SJ.gee tj-'ans-i-Kenthon ^ por -jd ντ.χ _β The gev / onneno li {jc ^ do i'T? ValniiiT ?. d «» ti?.! V5.oit and orgab 21 xyd, boiling point Aß am 6v> ° / 10 mm, f «3p« + 54.12 ° - χΐ 1.4471.

Böißpiol A-

g oinor i «-i; *: n!; lifi> i ' _S po2i-y ijaiiuiiumß and 200 al VfeaBer _? ''did;'"j.'3-Όρίοη t» {\ v.?i1ol ⁼ ? 3Hux'o enthioj. · ¹ : (pH do? solution * = 4 »0} _P w« r'io »/ P hour ³ - !! } -i '\ r: V' .- A ^r 5 ° h'öitiij {"oriihx-i :, 1« = »H.ydx ^s o" r7nooca.T5 '' - ⁱ Jf »Tj · = - Ihrlj, dr.u η \ ij Λον VScolvrng auaflol _? Wua'öo won by Ak ^- CIs.'ρ leren.uiid να & 19 _f ^! 3 β after the tumble in the air

"!: 13 bia 85 °). A" fully crystallized Pj: o1d3 lt 35 ΙΛ & 86 °): 'ci ^ - .; e Gins optiocho Drehuu ^; from Γα] «' β -.- <ί <1-ρ3 ''* DJ-3 Filt-rat y \ uä «nut RQ.iiPji oxtrahiort,

raaj? ?.? ₅ f; g ο Inas ilateriales won, dao 1 «Henthonopryy.lv; 3.Vc Di ο I ^ poxydxxeJction wiurde de ntillier 'in a vacuum; ιιγΛ ox'gal) 18.5 ß I-Hmxthsnepoxyd ,, boiling point 47 to 62 ° /! J ff: '. rfäj | ^b β + 541.38 *% nj ⁵ ^ 1.44ΩΟ _β Analysis dss HI-GI-Spok vn-ir '.- y dor gorö ^ Tilgten J? /? ob-:? .eigt® _f that it 100> ei · = · Gaa trans «1 - ne.athßjiopo» 3 "'y ^ä i was _£

009831/1885 _BAD ORIG.NAL

Example 5

50 g einoff i-lfenthenepoxydadschung wad 2C © ml of water, dae 5 drops of sulfuric acid (pH dor solution "1.5) was" the laiig 4 hours at 20 to 25 ° violently geslihzt * ₉ ~ DaB from

1 «Hydroxyneocarvojaentli®l% ms? de precipitating from the mixture obtained by filtration and weighed 28.7 g after drying in air (melting point 81 to 83 °) β Eine umkriatalli · = eierte P ^ obe (melting point 86 bio 87 °) aeigt® a © © p "llseae . Jörahung from [a] Jq "+ 45.5 °" Bac FA3.trat was with

Ψ ", r +« ^ «« «!; _υη α Q'jsgah 12.3 g of an Ifeterial @ _s

epoxy contained, - The spoxy was graphically cleaned. Analysis of the HKR spectrum of the cleaned sample showed that the 100% trans-epoxy was obtained from the Yalaiua distilled and gave 2Jg traas · "Mentheneposyd, Siido point 49 am 64 ° / 5 ° sm ₉ M ^ ³ " +50

OK **

py, p / ^ ,

OK **

«1,4-47

50 g of a 1 ™ menthi-4iieposydJ3iechung anä 200 ml ¥ aae © r ₅ the Tropfon icori? -9nt £ -: lo5th Ghlosfwasseratoff / acid contained CpH

η 2β O), was violent in 4 hours at 20Me 25 °.

g That which occurs from öor l ^ iecliun ^ 1

menthol was obtained and © duiicii Abfiltrioron. weighed 18 ^ 7 g after iOxockaen. in the air l [Schmslzx) unk: t 83 Mk 8 ^ °}. _e . A umifcTistallisiiirte Ps? Oli © (peeling point 86 -bit 87 °) te α ine opt Ib before i) 2 ^s eiuing of [eu | j = +44.7 ⁰ ^ The filtrate was with Hexas. e ^ -i; 2r-aliie.rt _E woboi mim 21 _p 7 g a © ® Materi les gewasÄLp da, "Yoy .'- ie ^ önd I-Menthensposyd was" Das! © tat called Epivxyd wuvöe gae chromatography sch -purified ? lyae of il-iP ^ Spoltti-mia d © 2 zeigt® purified sample ^ it lOOjBi.see ■ ^f - r £ ..7j.B - i "K9nthanepeaEyft aar · Di © gewoimon ©

nv / yr-'3ci 1 »-. Vacuum closed and yielded 15 _P 9 g

009831/1885

trans-1 ~ Menthenepo2eyä _t Kp «49 Ms 65 ° / 5 im, [ot] ^ = + 55.14 °, ο 1.4481.

Example 7

50 g of a 1 ^ mentheneposcyd mixture and 200 ml of water, containing 5 drops of 83jöiger Aaaeiaensaure (pH of the solution β 3.5) ₈ were vigorously stirred for 4 hours at 20 ° was through. Abfiltrioren obtained ^ after drying in the air 11p5 g of material (Ep. Β 87 Ma 88 °) with an optical rotation of ί®Ί $ ^& + 46.0 ° * The filtrate was extracted with hexane, where 21 1 g of material was obtained, which was predominantly 1-menthenep © xya. Base Epoayd was analyzed by gas chromatography of the ITMR spectra of the purified sample that a 1005% trajis epoxide was ₀ The gained "= ne Epo3cyd fraction was distilled in a vacuum and gave 15.2 g of trasis-1 ~ Henthen © po2yäp Kp κ 57 Ms 62 ° / 5 [a] | ⁵ «+ 55, O1 ° _v ώ | ³ = 1.4480,

Example 8

25 g of a 1-Hsnthenepoxydmiseimng and 200 ml of water were refluxed for 30 minutes. 1 "Hydro3, yneocarvomen" thol crystallized from the mixture on cooling and was obtained by filtration, after drying in the air 8.7 g were obtained material (mp. 84-85 ° *) · line uakristallisierte Prob® (Pp. "85 ms 86 °) showed an optical rotation of [cs] ^ s +44" ^ ⁰ * ^Because ß Piltrat was extracted with He ^ Zan ρ wherein one 13.9 g of a material gained ^ the "sa-Mienthanepoxyä fhielto the material was distilled under vacuum to give 6 g 1O ₉ I-Menthenepoxyd, Kp, Ms = 55 74 ° / 5 mm ₉ n | p * 1.4477 , [a] ^ ⁵ "+ 51.02 °. analysis showed dee NMK spectrum .the purified sample that ee trans-i-Menthenepoxyd was ₀

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Example 9

A kisihuag of 20 g of eiaoo I-Menthenepoxydgeiaiechee, 100 ml of Vfassec and 1 g of sodium carbonate was refluxed for 5 days, the mixture had a pH ύοώ. 12. While cooling aar Hi. ß el π vag dropped out 1 »Kydroxyneocarvoaienthol. The Pesteubstaiis wu.rde öureli filtration recovered and returned to ä3m Sr oßlmon in air 4.9 g of I-laterlal (Fp, "84-8 ° ^e j) (, s mp 35-86 °) had _o 25Aäo ujakxiatalllolaxte Proba an optical dröhtmg voja [ ^a lj) ' ^{) s} +44 »4 · ° * The' gluttonous piItrate was won with Hu; can ©.-rfcraiiies-fc, where 14 _f 2 g of a materia · = los & nn & n \ no; ami _t aas vorwiogenä 1 "" contained manthenic epoxide

dos materialc-s by vacuum distillation gave 8 _P 4 g of I-Hentlianäpösyd, Ep «3? Mb 67 ° / 5 am, [e] S ⁵ = + 51.84 °, a £ s 1 _P 447S _O Analysis of the MMRoSpelstruias of the purified Px-above indicated that it is 3 * 3 $ from de- and 67 #

The Epojtydgeraiscb is used in the cases 10 to 16. obtained by Persä-d3? eex) o3qidatio2i of (+) - liraons according to known methods and the EpoaeydgeiaiBch possessed the following characteristics [ei] ^ ⁵ «+ δίρΐβ ⁰ , n | ⁵ «1 _P 4653, 50 fS ice and 50 ^

Example 10

A mixture of 50 g of a mononepoxy mixture, 200 ml Water and 5 drops ■ perchloric acid (pH of the solution> 4.0) was vigorously stirred for 7 hours at 6 °. 1-Hydroa ^ neodihydrocarvQol was collected by filtration and weighed after drying in the air 14 »9 g (2? p ·» 65 to 66 °) ♦ One Sample v / ujpde UBürrl installed (Pp. «= 67 to 68 °) and showed

^ ⁵ β + 423 °

an optical rotation of [<* 3β ^β +42.3. The aqueous solution that emerged from the solution was extracted with hexane and orgs.b 16 _S 2 g of material. This material was vacuumed

00 983 1/1885

distilled and erg & b 14 _t 2 g Limito ^ uepoxyd, Xp «> β 59 to 70 ° / 5 rom, [α] *** -; 75, ΟΘ °, n | p« 1 "4648. MMR-Analyee 3er ffrob ^ ?, Increased "that si" to 21 _P 4% from "is- and; ? 8.8 # consisted of trasse-Lime epoxide,

Example 11

A mixture of 50 q of a lime epoxide mixture, 200 water and 5 drops of perchloric acid (pH of the solution «4 ₃ i))

was stirred vigorously for 3 hours at 20 bio 25 ° .7 ~ f-Hydroxyneodihydrocanreol was isolated by filtering off and weighed after the overhaul an aar 24.8 g (? p _e β 65 bio 67 °). A sample was unused 68) and showed an optical srehuag ύ & π [<The aqueous film a "s öer E * saktion" iaisöhuiig hexane extrriil't, whereby ffiaa 17 _D 8 g of material

wurdf ISS doet.illiejrfc vacuum to give 15 _s ig p ^ ₆ Kp e 64 to 71 ° / ^l 3 βγλ, FCS3 *>"+ 75.54 °, z: β 1p4f> 52e NMR ^ Analyae dea JBpoxydee aeigte that

Example 12

A hicchuc ^ of 50 g of a MmonenepoXydgeaiiscaeis ,,>'ί> ml V / aestjr and 5 drops of percMoric acid (p!' I der Xiöeuxi ^ 4.0) was vigorously irritated for 1 hour at 40 ° «Bjdj neodihydroca3 ^T \ rsiol viurde by Ab.filtri © raxi g © ^ ssnoa * αη * Λ yielded na oh deir · S-'arcßlmen an der L« it 343 SC ^ P »~ ^ 5 bf 68 °) * A £ robe was recrystallized (Fo. 67 Hfe · and possessed an optical rotation of l'elp ³ ® ■ ^f -43 _f 4 ^<> 9 J * 'i £ aqueous solution c-wh of the reacti.oüBmiechuuvi ' W & züe with extracted, v / obei man 15 »1 e I-Jatorial gevagm» terial \ mi? do ia vacuum äaptJllierfc uuci eiegals 8.7 g epoxyd _f Kp. r, - 63 Mo 70 ° / * shs _p [ej ^ ⁵ b + 76.64 ⁰ , ii | 1.4650c ίΠΙίΙ'-ΆΏ.αΙνκβ showed "sat ia." I? PoxyÄ löO ^ igsa trsae "Isomerβο iur"

009831/1885

BATH ORIGINAL

Example 13

A mixture of 50 g of a Lim © ii © a, <ap © 3cy <äg®ntiisehee, 200 ml of water and 5 drops of perchloric acid (pH d®r solution = 4.0) was stirred for 10 minutes at 60 °. The mixture It was cooled and filtered, whereby 52.0% of hydrocarveol was obtained (pp. 63 to 65 °). "A sample was crystallized by" crys- tally (S ¹ P. "65 to 66 °)

The sample had an "optical rotation of [«] $ <* +42 ₉ 2 ° ". The aqueous filtrate of the Röaktionomiechung was extracted with Hea ^ a © xtra-", 10.7 g of material was obtained. This material

It was generally distilled in a vacuum and gave 5.1 g bp, 55 to 72 ° / 5 never, [a] ^ ⁵ "+ 73.22 ° _f. B ^ ³ " i _t 4649

YIHR analysis of Spoxydoe showed that there were 10biges aoree was.

Example H

iSino MlsGhuTig aius 50 g of a Llmononepo ^ dgeiaisches »2Ä * sal Viasßor um * 1 Tz-apZmx sulfuric acid (pH cte KSeimg β 1 _P 5} \ iurde I ₀ 5 hours long up to 20 Ms 25 ° vigorously stirred„ Di ^ aiiBgefickt® P -astaiibstanz wuxd © by filter-i © r © a isoli © 2r "-v _c ■ es SSgS £; 'ä ^ Hyd ^ o ^ Taeoäihydröc ^ yveol © sgab (lp _e » 66' bie P «j-1 ^y ) o 2 £ ae Riob «viuxrd © usskrietallißiert (S ¹ Pe θ 66 Mg 67 ^s ) _f ,

ΐί, ο uiElirEistalliaiorte Prob © shows © a® © ptisöb, ®

-f42 _s 3 ° _e Dae aqueous IPIllat came out; d © ^ Raaifti

e a5.t Hoxaxi © xfcraliiort _p wofcoi ßaa 17 «? g I g Dioiies material totö® in Takuuai

resulted in 13 _& 0 g Lteonenepos ^ ydi Kp ₀ s β5 "bit 70 ° / 5 ^{5 0} , _y a | p» 1,4β50 _ο HMR «ÄziAlyse geiges ₉ that

the P2-r © "ö © sy 1 * 3 fJ o.us eis" urni 85 % off

009831/1885

~ 16
Example 15

A mixture of 50 g of a Mmonenepoxyd ^ emlschee, 200 ml Waseer and 7 crimping 88 # formic acid CpH the solution "3 John) was for 3 hours vigorously g at 20 ° €,> stirred _e The aqueous layer was pll 3» I ^ Hydroxyneodihydj Carveol was isolated by filtration and weighed 17.7 g after drying on dor LuiTt (m.p. 66 to 68 °). The sample became usicrystalline (m.p.

from [«] -p β +44» 2 °. The filtrate was extracted old hexane, which gave 21.6 g of 2 & ateriaX ®rg ₉ daa was predominantly jimonenepo ^ yd · Material was distilled in a vacuum and gave 17.6 g bp "s" 65 to 74/5 nm ₉ [β] ί ' ^β +75.3

r ts 1 _e 4652 »HME analysis άβκ ¹ sample showed that si © too

16 a 7 fi from clß- and Θ3 _β 3 ^ from trans-Liiaon & nepoayci bastand Example 16

A mixture _e cooked 20 g Limonenepo ^ de and 100 ml Waaser contained ρ wurd® for 5 minutes at reflux. The mixture was cooled down v / imie, urobal 6.9 g of 1 "Hydroxyneodlhydrocarveol ame" fell (MP ₀ "63 to 65 °)""A sample was umkrietallißlert (Ppο s 6 ^ to 66 °) and b © B & 3 eiae optical rotation of [tx] jp s +41 ₉ 3 ° _O DA® aqueous filtrate was extracted old hexane what _t ck 9) 6 g © material, the predominantly Limonenepoxyd was. The material was de-diluted in vacuo and yielded 4.9 g of simonene epoxide, Ep, «66 at 70 ° / 5 am, [α]? ⁵ e +72, ' ^? a °, n £ ^x »Jp4641 ο ai3R» tog.lyae döx * sample showed that they su 16j7 fo aua eis «and 83» 3 $ from tran &-> Llmonenepoxyd beetaneU

in the Beiepielen 17 and 18, the Epoxjdgeaiech durcfe Persäureepoxydation of (i) '= is - obtained 3- menthene ^e, ea Ik sat following Charakteriötikas n ^ β 1.4452, 72 # and 28 CIE ^ trans "Eposyd _o

009831/1885

l, 17

17 -

A Misscfrimg from 20 g a © a (i) - => 3 ^ei Meatliör.opo3 ^ dgenilschea, 100 ml Waaö® »u & d 3 Kröpper perchloric acid '(pH of the solution κ- · 2.5} was © for 3 hours to 40 . violently stirred ° The mixture was cooled ₉ wherein 2.6 g of 4 ~ H; ydrGxyneojnenthol precipitated (S ⁸ Po θ 68-69 °) extracted _o Bas imrds filtrate with hexane, and orgab 13 "3" g material which comprises a mixture aua Spos ^ d and 4- "Hydra3yrieo2iaiithol represented * The mixture was distilled in vacuo to give 3.2 g iiian (-). '3' sposcyd geiiiyuie- £ p _a" = 55 ms 52 ° / 9 BIIa ₅ zi, £ ^ <= 1S445

inalyse flea purified Epexydes showed _β that the sample

was »

Example 18

A mixture of 20 g of one! «» {^ J ^ «nd 100 al of water was shed for 15 hours. Reflux-boiled The mixture was cooled and filtered to give wm, 8.0 g of 4 ~ Hydroxyneoiaeathol (fp * "68 biö 69 °) were to win, the filtrate was xtrahiert with Hssan © _B which 10.1 g of material revealed aas voniiegond 3 = ⁵ KfinthenepO3yd ^ ar »Dae material was deatillie & t in a vacuum and» r-gave 7 _S 5 g ^ -Menthei.epoa ^ d, Kp ₀ «68 to 75 ° / 5 μά ₉ ajp · 1.4519. HMR analysis showed that the purified sample consisted of 17 ^ aua eis · = »and 63 # of traas = epoxy,

A solution of 50 g of tsans <-1 "Hentheno2yd and 50 ml of acetic acid was stirred for 8 hours at low temperature, Qas-Ghxomatc-graphiacho analysis of the reaction loop showed the Abitfaeenheit Ton Bpojcyd and the formation of a new main product The solution was poured into 200 ml of waster and extracted with hexane ₀ After washing, de "extract with

009831/1885

«18 ~

watery alkali and tinting of the organ-fled layer tibea? anhydrous sodium sulphate, the solvent was ^{removed under 1} vexzainderteoL pressure, whereby wni 56 _s 6 & 1 «=> Hydroxyaeo» received carvoaumethyl acetate, the identity of which was determined by the gaa => chromatograph! οchen Siitentionesselten and fJ.e InfraredepeJr = loyal, lied to v / urcto »

Example 20

A Geminch from c £ o "~ uua trane-1-menthßnejsoxyden was selectively hydratioiext to the in the example 1 to 9 beeehriebeno Weis ©. After the separation deö traiiß ^ E ^ os ^ disoraören • jnirdö aau by selective Hyd3. * Ssl? Jleriiiag ¹ J ^ OB eis-t-Mentheaepoxyd oxhaltonc i-Hyd ^ ojqyu.socarvniEeathol au I-Hydroaeyse * - ca.rwoinei !. thylöc «ta ^: 'acötyliert = DI © Acetyl:. © rung wsTüe carried out s Jjideia aisja a © Mlociiiing aua 5.1.6 g 1-Hföroxyneocarvomonthol, 300 ral Eesigßäu3? e _F 36 g ace-aaliydrid and 1 ^f f f sodium aoetate by 16 «®tündlg © ß heating the miochung to 100 ° UELROtr; to, Bio Ilieehuug was cooled, in 500 m.1 water gGgoosi-n upd iRit Eoτα« ^ .- radiated "-wosei man 62 _f Q g

Bnispie ?. 21

t M-O g) me each at 480 to

300 ° ni'i oise-r Gösoh Speed of 24 Ss ^ sCjs bs?

5.r »c £ i5 g € Rcuiclft _f . öas sit G-ieelaolf ^ ae of

O "635 C3.1 Ei'7'ι- · ai'.MfifjQ. '?? (1/4 λ »αΑ>) filled ®af _f lacii the passage de?. * Urri ~ vr.i« 1 ^ 3 through dio B '^ i.onae WUE ^- -Se di-s Soloüne üsit benzene f, ov * ^: ^ C'5on _f u ^? n äif? letv; vr ορυτοϊ? ai ^ - '? & fii? .i' :: t, au en * - f «rnen _o ra ¹ ? yroduki- was with I ^f "Λ * urmvöro rylSs ^ irvg geva ^ nbcn, uw cben>" a "J! ifi etitnva-jdcniC Eeai ^ i.« ?. "» ure yu EeiircallEiaven un.d after de: ^ Ei. -t.feimu: ^ des Iiciau7? 33 ^.! ttelo were 1 ' ⁷ _? 6 g '-iaterial β?.' Ϊ́ ^Λ - <ΐΛί »η- GaQciirorafeoijraiplii ^ oh ^ / mal fee sedgii: - that

009831/1885 BADORiGlNAL

• The product mixture consisted mainly of tran8 ~ 2-menthen-1 ~ ol.

Example 22

A 1: 1 mixture of cis and trans-limonene-1 _t 2-epoxides (2910 g) was stirred under reflux in 3 liters of water for 24 hours. The mixture was cooled and filtered to give 1471 g of 1-hydroxyneodihydroearveol and, after hexane extraction, 1076 g of tranß-hmonene-1,2-epoacyd. Part of the 1-Hydroxyneodihydrocarveole (100 g) was refluxed over Hacht in a mixture of 70 g acetic anhydride, 25 g Hatrlumacetat and 170 ml benzene. The mixture was neutralized by washing the organic layer with aqueous alkali. After removing most of the solvent, 136.8 g of crude I-hydroxyneodiliydrocarvyl acetate contaminated with about 10 ow benzene were obtained, which was subsequently obtained by pyrolysis trane-2s8 "p ~ menthadien-1-ol could be converted"

Example 23

Pyrolysis of 1-Hydroxyneodihydrocarvylacetat (112 g) at 480 °, on ShnlichG Vieiee as in Example 21 carried ühr-fc "yielded a pyrolysate, dae 2 _f 8-p-menthadiene ~ 1-ol ale main" product contained ο Hach the vacuum distillation 37 £ 2 ₉ 8-p-menthadiene "= 1-ol, 17 g of recovered 1-hydroxydi" hydrocarvyl acetate and about θ g of hydrocarbon were obtained. The 2, S «p =. Menthadien-1-ol boiled in a boiling range of 71 bio 80 ° / 3 mm and its spectral data confirmed its identity». .

The here for the determination of the cie / trane-EpoxydieomereverSsä-lt The analytical method used for the isomeric epoxides establishes ai \ f the ratio of the integrals of the protons "

009831/1885

- 20 signals in the NMR spectra of the mixtures.

The NMR - = - spectra of the two isomers dee I-menthenepoxide show a similarity that is not unexpected. In both epoxides, the methyl substituent on the oxyranngine system appears as a slanglet at 8.78T and the methyl groups of the propylene radical appear as a doublet at 9.16T (center, 5.4 Hz) with only a very small difference in the chemical shift Differentiation of the two isomers in a mixture. The methylenite carbon atoms on the saturated carbon atom appear in both isomers as unresolved signals from 7.8 to 9, OT «The two isomers can, however, easily be distinguished by the resonance signal for the proton in the 2-position of the oxirane ring system. The cis-epoxide shows a poorly resolved iriplet at 7.17T, while the trans «epoxy isomer shows a doublet (Ja * 5 Hz) centered at 7.21 ΊΓ . Integration of the peaks, which correspond to the oxirane proton of the corresponding isomer in the mixture, simply gives the desired relative ratio,

The assessment of the isomer ratio of limonene-1,2-epoxides can easily be carried out by integrating the suitable proton resonance absorptions in the HHR spectrum of the mixture, analogously to the catfish described for the Henthenepoxide isomers. The methyl group attached to the Oxlranrlng either the ice "or the trans isomer tied 1st, appears as a Slngulett in the NMR spectrum of the cis isomer at 8.79 ¹ T" and the trans isomer at 8.77 In the spectrum of a mixture of cis and trana isomers, these peaks are clearly resolved, which allows a precise assessment of the isomer ratio by integration. In addition, the proton of the Oxlranrlngeyetemes of each of the two isomers is sufficiently well separated from the other, so that a precise analysis by integration is possible _o

009831/1885

The JUiailyaa of the mixture of the isomeric 3-Htmthenepoxyde can AUGH by integration of the signal for the proton at the Qx iranxlng slnos joden of the isomeric epoxides analogous to that described above for the Limonon »and 1-Mcnthenepoxyde manner duTöhgetührt. The oxirane ring proton de "trane""3" lteii " thoiiepo2sydes appears as a doublet ( 3 ^ 5 _t O Ha) at 3ρ 22 ^r C, while the cis-looaer oxirane ring proton a poorly resolved triplet (J ^ -1.5 Ha) at 3.21 T actual.

009831/1885

Claims (1)

Pe tentanoprtiohe 1 / A method aur Srennune elnea (lemiechee than and of a tear ·· taomeren 1 _r 2 epo3cyeyclohexenen of 1.4 ~ oil & lkyl "or, in AXkyl of 1-" 4-alkenyl-1,2-epoxy-cyclohexanone in that Λαο (ro: ni.ach isit V / aeeer is treated, whereby the cle «-lBOiuo7-'c is converted into the corresponding 1,2-diol, while duo trans-Ißoaero remains unchanged, and then the tranu« * looicioro voai 1 , 2-3) 1 oil is separated. 2. Process according to Anoprvich 1, characterized in that the 1 ₁ 4-dialcyl-i, 2 ~ opoxycyclohexene and 1-alkyl - ^ - alkenjl-i, 2-epoxycyclohexane epoxides of compounds of the terpene relhe alnd « ? · Verfaliron according to JUiapruoh 2, characterized by the fact that the epic is an upoxide of the 1-IIenthonn ₉ ? - »menthene or · let. 4 «Method U (HiIi oinoia of the preceding claims, thereby G« iaennfceichnii "fc, äe.! I the treatment under eauron conditions 5 «Verfalu: s according to claim 4 _{0 9} characterized in that the Bohoiiillutvs in the presence of OhlorwaaoeretoffBäure ₈ SchKöfelßaux'vO, PSRE -hlorBr.nj ^ * ^ ode j. AineiooneUure is durchgefi'bxt. 6 method according to Anapruch 4 or 5, characterized in that that the SHuro is used in advance 3xieiuiri. 7, Yoi'fßhx-on naf-h Anapruclx 6 _P characterized in that old-Säu-vo oiiiö ICotüsentratJon from 0 _{s to} 01 to 15.0 56 beaitat _e 0 0 9 8 3 1/18 8 5 _{BAD 0RiG | NAL} 8 * VQt'iehv-mi .r «.acii one of the treatments 4 to 7 _B characterized by the fact that the treatment is carried out at a pH of at least one. 9r ancestors ».aoh oiiism öer Annpi * üche 4 tie 8, characterized in that the treatment is carried out at a temperature of ^{0 to} 65 ° C. "Ο * X * ^f experie M NaOH a άοτ Anoprltclie 4 to 9» characterized ge "krtTiniseiftlmot _t Oich that the treatment over a period of 5 to Iliauton O stretched ₅ O Stimden 'Hey procedure? Yes ;; can be. of ¹ ArAsprüche 1 to 3, characterized k _<c aimzeichnot that d.io treatment under neutral conditions ■ • .iurchgeführt wiycL 12. The method uacii claim 11, characterized-dafl öio Behojßdlvj ^ g · bo.t one 2omi> <& rstur from 4G to 150G will lead. 13β ancestors by Anopruoh 12, characterized _s gekennaeiohnet the Tc-apojralur · b * ji 75 biij 12O ⁰ O lies. 14 "Vorfaliron roof one of the claims 10 to DS _9, characterized in that the treatment is carried out over a period of τοη 10 minutes long 48 hours * 15 «Procurator K.aoh one of the claims % bie 3 _P characterized by the fact that the treatment was carried out under alkaline conditions ^ Yi2.'d · 16o to Yerfatiran. Claim 15, characterized gekemizeicbaet that the Bahaadlung in the presence of sodium carbonate, aqueous Kaliumhydroxyfl οΛβχ aqueous sodium hydroxide conducted wi.r "ie 009831/1885 ϊι iiaeh claim Vi-We ü 16, characterized in that dl _P © treatment "be.1 performed in pH of up au 12 18o Y © 2? £ * AHI eii according sinoiA dor AssprUche 15 to 17 characterized ge ₀ · kenneeiohaetf that the üahandlufig bol! A Seaperatur -yon 70-1! 50 ⁰ O performed v / ith _o 19 * Veriahson according to claim 18, daduiich gelceinnäaiehnei ,. daö dio IBenipeseatia 'obisiml'b 95 ⁰ C is, 20 »Verfaiiron Eiach oinern de ?? Claim 15 to 19 »thereby ge · keimaailckaet ,, ä% & sich die treatment tfbai. ' © Inen S5eitraue ¥ 071 1 E3g "bio 14 legends streekt _o n according to sinam of ^ ro ^ he ^ gezideu claims, thereby galcBSBiiäelclmats that daa traiio ^ XßoiB-era the 1,4 ιγοϊι äesa aiiu dea aureh 22 ₃ Ts ^ aliröii aaoh addressed 2I ₉ thereby g © ki8aaseii \ ö.G.ei " _y di.e i'ijcamiiig atifgsuM der Lösli
acydofj imd des 3) 1 oleo duröhgefühsrb 2 ^ o \ ^r es £ ahSQXL after Asapaiueh 2I ₁ , thereby gakasmaeXelaaet that the 2? Joaiau «iS dw3fnk «Rn carried out BATH ORIGINAL 009831/1885 190827 a -a.tn t ^ aas süas? - sin trams-1 «• ΑΧ ö 2 > 1 ^ öa ο Sea? © la t below 4aS as a" 27 ο Vssfateen sash. Asispgualx 2S ₆ -dadureh gekeimssielinei; _? the solaktiv © ¥ © 3? a8t © 3MS33g JaI ^ Aoetylchloriag. Acstaöliycl3? 14 orlai? B. 28 »Torfaio? #N xiaeii alnsn der g & k®mxz & icime% _v öaß @; ia molares-10 $ iHMsrsehmß am ls to 27 _P. less than 29ο "-Tosfahraa-» ach. One & i der j that. that there © ^: t ^ aB ^ «1 s. © in © TesMadimg der Ms 28 -is _e ice «" uad ,, that © in. -the end- 009831/1885 BAD GRIGiNAL, 190S274 ■ # ■■: ■■ -, ... ■ from ül & - uuä ti-acc-'Jjia, x ^ ^ dem Yevtüh ^ n össv Mcpzt · ^. «-. 1 b.lö Z% ßfitx'esmt..will ,, das die, u «" 1 «-ol py 32t trftne «2 ~ lfcj-ttiia ^ 4 <~ 0! unc! t 34ο ¥ orfsliircri after iji »p3: -i \ Cifi 55 $. daciu ^ ci gek "e.vmiioich}}. ot, A &'J> tst \ d.rcl and the ßel) J / Tnol; i 009831/1885 .-'- ■■ 'BAD ORIGINAL