DE2256506A1 - PROCESS FOR THE PRODUCTION OF ETHERS FROM PHENOLS AND ALKYL POLYOLS - Google Patents

Description

PATENTANWÄLTE DIPL.-INS. R. SPLANEMANN dipl-chem. or. B. REITZNER - dipl-ins. J. JUDGE

MUNICH HAMBURQ

16o HOVo 1972

Cheraetron Corporation eooo Munich

111 East Wacker Drive,

' Telegrams! Inventius Munich

Chicago, Illinois (V.St, Ao) 15t3 - I - 8049

Patent application

Process for the production of jfohern ^ au a phenol and. Alkyl polyols

The invention relates to a method © !! % m? Production of aromatic ethers from Folyhjdrosyalkoholeno cheap © these ethers are used in the Meöisia _p ®isisahli © 31iefe i © r human medicine and the Tiemefäisii & s s © as for purposes »It was iB

guajaoolat or 3 ~ (oM © tliO3sypfe, © 3S © 2Sj) -1 _& 2-propaiiäia2 'and 3- (o4Poloxy) -1 (, 2-propasiliol "when used on people and! Piere muscle-relaxing © properties have _α 11 © the first-mentioned compound will continue to be known as »In the cosmetics industry we are

1,2-propanediol in some

The HerstelluHg of HardsposyalfeyHtlaeria VÖH Ptenolea is untssreueiit ready for several years to the ever nioht in link long to be brought objectives (verbessert® off / booties, higher purity and Wirtsehaftliohkeit) to achieve an optimal way, "Di © üblieh © s? W @ £ @@ applied reaction is the condensation of a phenol with a

309822 / 11S9

Halohydrin in the presence of an alkali hydroxide or -alkoxida. The .Reaktion τοη phenol with Äthylenohlorhydrin can, for example, by the equation

NaOH C ₆ H ₅ OH + ClCH ₂ CH ₂ OH ^ C ₆ H ₅ OCH ₂ CH ₂ OH + HaCl

be visualized. Probably an alkali phenolate formed as an intermediate. Genre of invention this reaction is used with advantage to produce an Xther with high purity in economic yields to obtain.

In a known process for the preparation of these phenol ethers, the reaction is carried out in an aqueous solution. As a result of the large amounts of water required, however, there are great losses of halohydrin, since this hydrolyzes. Furthermore, undesired halides are introduced into the final product by the water, from which they can only be removed with great difficulty. To turn this difficulty "already äthanolisohe solutions HatriumHthoxid were used (J ₀ Am.Chem," Soc "72, 3710 (1950)) _o Am disadvantage of this process on an industrial scale is is that the NatriumHthoxid difficult to manage, with the help the process according to the invention overcomes the difficulties encountered with the salts without this disadvantage

309822/1159

It is has also been made known "an anhydrous sodium, the dee by azeotropic distillation of the Wassere from an aqueous solution phenolates with toluene _β of condensation with a chlorohydrin asu use (British Patent 788,278) In this method, however, special precautions are necessary, to prevent the sodium phenate from caking in the final stages of drainage; Furthermore, excess reaction participants and by-products must be removed from the condensation product either by steam distillation or by repeated recrystallization.

The process according to the invention is particularly suitable for the production of glyceryl guaiacolate with a high degree of purity the method described in CSSR patent specification 107 107 _; .. in which an aqueous solution of the crude Glycerylguajaeolats is dried azeotropically by distillation with a single organic solvent, which also serves as a crystallization medium, melts between 78 and 82 ⁰ Co. In the process according to the CSSR patent 109 881 is an alcoholic medium used, whereby glyceryl guaiacolate with a melting point of 77 to 80 ⁰ C is obtained o

309822/1159

In the process according to the invention _9, in which ethers are obtained from phenols and polyols in high purity by a single crystallization, mixtures of benzene solvents and alkanols are used during the entire process, ie during the dehydration of an alkali phenolate, during the reaction with the alkali phenolate a halohydrin and the ether obtained during the recrystallization »

The invention therefore aims at once sin process for preparing a crystalline \ there from a phenol and an Poljol eat high purity _p without recrystallization is necessary "Furthermore, to the crystalline ether / OHL prepared using the same solvent mixture 3ov be as well purified <> Furthermore, in the process according to the invention, the solvent mixture used is used as a component in the azeotropic distillation to remove the water from the Heaktlonsgemiechj, as a solvent (together with a very small amount of water) for the alkali phenolate and as a solvent for the * crystallization of the ether will.

These and other goals and benefits arise from the description below.

In general, the invention relates to a process for the preparation of a crystalline ether from a phenol and an alkyl polyol characterized by that an aqueous solution of a phenol and a basic alkali compound is obtained by azeotropic distillation with a mixture of a monocyclic benzene solvent (i.e. benzene, alkylbenzenes and / or

3 09822/1159

22565

Alkosybenzenes) with 6 to to carbon atoms and an alkanol with 4 Ms 8 carbon atoms are dehydrated, the alltaliphenolate formed is reacted with a halogenated hydrin at the reflux temperature of the mixture and the ether BXiB is crystallized in the mixture obtained

The foensol solvents used include hydrocarbons such as benzene, toluene, xylenes ρ xthylbene sol ρ cumene, kssityl © B _p cymene, diethylitbenzol, - but, yi "bcn-sol and phenylethsr _s v / le Anisole * Yon aießen Ijösimgömittsla vjerßea B © ns.öl _g toluene and di © lylolö because of iiirsx? Lower boiling points, before ^ sogt used; Sfoluol uad di® xylene © are a & cM because of their lower 3f02 £ ig.

Among the erfiadungsgemäß verwendbareifi alkanol © fall n-butanol eek-ßutanol, Jsobutanol and mixtures thereof ■ "V / urther examples Fuei ⁵ alkanols are the pantaiiOie, Hexanoleρ heptanols and Octanoleo This can be either geradkattige or branched compounds handelnj z" B. n-Octanol and 2 "ethylhexanol-1 _o Preferably at least one compound from the group n-butasiol ₉ ssk-butanol and isobutanol is used as the alkanol

A particularly preferred solvent mixture contains toluene and a butanol _s insbasondero n-butanolo

The ratio between the benzene solvent and the alcohol in the solvent mixture can be between about 90 and about 10:90 parts by volume. Mixtures in which the Bonaolischa solvent is the main constituent, however, are preferably _D to halohydroylcinvarluata, dio by the reaction with the alkanol

J ü ü 8 2 2/1 1 5 9

., 6 are conditional »keep as low as possible.

For the reason there is a YerMltnia of 90 parts by volume benzene solvent as 10 vol% alkanol especially preventive, although good results also with Volumverliriltnlsaesi in the range of about 80s20 to about 60? 40 e /. 'Can be held "

The phenol can be expressed by the formula

-yy-

(YIi) _n

Icenri55: oichnon _f in which R is an alkyl or alkoxy radical with 1 to 4 carbon atoms "halogen or a fonyl rust and Y oxygen or sulfur thereof" nd where ra = 0 to 5 } η 1 to 3 and ia ·! - η not greater than 6 The phenol must preferably contain phenols in the hydroxyl group. several hydroxyl groups sensitive to atmospheric oxygen aiiid. Phenols having 12 or less carbon atoms are also preferred. Usually the phenol contains about 10 or less, more often 8 or less carbon atoms. The halophenols which are preferably used contain no more than about 2 Halogenaubatltuentan and hHuCigar only one Halogensubatltuenten. The preferred fluorescent substituent is Chloro Doaonds. Preferred are the alkoxyphenols

', St., ü 8 22/11

BAt) ORIOINAL

Examples of phenols which can be used according to the invention are phenol, thiophenes, cresol, p (t-butyl) phenol. Chlorophenols ihiocresol, phenylphenol _t ethoxyphenol and methoxyphenol »

The polyol content d @ 3? Ether © rfindungsgsmäg produced may be derived from a di-, Sri or hühexreia Hydroxyalkanol (a, B 'mannitol) _β The Realctioneteilnehmer, this proportion is introduced in the ether through which is corresponding to the polyol! ^ C-Monohalogenhydrino In connection with the present application, under the terms Kalogenhydrin, Chlorhydria, bromine = hydriii etc _e those Poljole be understood in deaem eire © ·? the hydrosyl radicals is replaced by a chlorine _Β bromine or another halogenated ο

The eC ^ Monohalohydrisie usually contain no more than about 5 _tons, preferably only 3 or less hydroxyl residues «The Ansah! the carbon atoms is usually 6 or less, preferably 4 or less. Most often they contain 2 or 3 carbon atoms. The preferred halohydrins are the chlorohydrins and brorohydrins, although the corresponding fluorine and iodine compounds can also be used «

As examples of respondents by the the Polyol portion is introduced into the Ättoer, are the

oC-monohalohydrins of ethylene glycol, propylene glycol, isobutylene glycol , glycerine _s 2-methyl-i, 2 _S 3 »propanetriols 1,2-diraethyl-1» 2 «3-propanetriol, 1-methyl-1p2j, 3 = -propantriolρ called mannitol and sorbitol

309822/1159

θ -

Those necessary to form the desired product Atoichiometric amounts of the halohydrins and the phenols are preferably chosen so that the amount the impurities in the product is reduced «For example, one mole of a dihydroxybenzenes reacts with two halohydrins to form one to ether ο

The basic allcaline compound, the sur production dee If the appropriate phenol is used, it can be lithium, sodium or potassium hydroxide.

The basic alkali compound and the phenol are in a mixture of water and the mixture of benzoliechera Brought solvent and alkanol, whereupon the mixture is dehydrated by azeotropic distillation; here the mixture of benzene solvent and alkanol is continuously added to the after the water has been separated off Returned reaction vessel. The distillation is carried out until practically all of the water is removed from the solvent. At this stage Care should be taken to ensure that no alkali metal phenolate is precipitated ο If such a precipitation takes place “so can start adding the halohydrins as soon as the first precipitate can be seen. In some Cases can reach up to about 10 moI- ^ dee through the Reaction of the alkali hydroxide and the phenol formed water removed together with the solvent water before precipitation begins.

309822/1

The halohydrin is practically completely dehydrated Solution of the alkali phenolate added, whereupon the removal of the Sestwassera is completed.

Under reflux temperature within the meaning of the present invention one understands the temperature at which a return flow of the mixture of benzene solvent and Alkanol occurs »This temperature depends on the pressure in the Distilliervorriohtungs.dem in each case used Solvent mixture and its amount. The reflux temperature can occur as a result of fluctuations in heat input and heat dissipation during a reaction in to fluctuate a few degrees in a certain system »

The weight of the Lösußgsmittelgeiaisehos usually about 1 to 20 χ as high as the weight of the product to be produced "Preferably, this ratio is between 2 and about s1 1OsI Gewiohtsteil @ n _ff particular between about 4s 1 and about 10: 1 Gev / iohtsteileno

The time available for the dehydration stage of the process is not critical »This time can vary depending on the temperature in the system _9, the solvents and the pressure, and is also not critical» The reaction of the halohydrin with the alkali phenolate is often within one Period of about 1 to about 8 hours, more often "ended within a period of about 2 to about 6 hours"

309822/1159

After the end of the reaction or at a desired point in time before it, the reaction mixture is acidified with a suitable acid, e.g. caused by an alkali phenolate with a low solubility in the solvent mixture used, avoided o If water is introduced together with the acid , this is in turn removed by azeotropic distillation «. In order to achieve optimal results, it is necessary to practically remove the acidified V / anaer from the acidified reaction mixture. The quality of the product and the yield are impaired by the presence of water in the solvent mixture during the crystallization stage. The alkali halide formed during the condensation is carried over into the final product by the water.

Preferably, the reaction vessel should be kept under a nitrogen atmosphere or until after acidification be kept under a different inert gas.

The alkali halide is then removed from the product solution, whereupon the product crystallizes out. The crystals can be separated off from the mother liquor in any way, for example by filtration or by centrifugation. The mother liquor can be evaporated even further, crystals again being obtained which are added to a dry solution of a subsequent batch of the product.

309822 / 11S9

The following examples illustrate the implementation and the advantages of the invention o All parts relate to on weight; if nothing else is said »

A reaction vessel equipped with a cooler and a water trap is charged with 159 parts of toluene, 17 parts of n-butanol and 8 ^ 5 parts (O ₉ 215 mol) of sodium hydroxide in 33 parts of distilled water. Material flow passed through the mixture "to displace the air present in the system" Then 25 parts (0.202 Hol) of guaiacol are added, whereupon the mixture is heated for about 4 9 5 hours at the reflux temperature of 83 to 98 ° G "with 32 parts of water Distill azeotropically from the mixture. The toluene and n-butanol are continuously returned to the reaction vessel from the water trap in which the water is separated off. Then 22.25 parts (0.11 mol) of glycerol chlorohydrin (3-chloro-1, 2-propanol) are added at a temperature (in the reaction mixture of about 90 to 95 ° C. The mixture obtained is then about 4 hours under The mixture is then heated to reflux by adding 1 part of concentrated hydrochloric acid to a pH of about 1. After the nitrogen purging has been interrupted, the mixture is dried by a final azeotropic distillation. "

309822/1159

Dae mixture is stirred at ett? A 6O ⁰ O ffiltriert to the formed in the reaction sodium chloride to remove · Bas FiItrat take ?, at about 68 C erhitsst _t anschießend over a time ^ aura of about 50 Hinuten at 40 ⁰ C cooled ν, νύ kept under stirring for about 25 minutes at 40 ⁰ C. the solution _e viljM having about 0 _s 1 parts ßlyceryl "guajo.e0la.t - Erißt ^ cases inoculated _p mn aetisen crystallization in Gaeg 3U" the temperature is raised to about 30 minutes 40 ^{° C. and then reduced to 6 °} C. in about 2 hours »The crystalline mass is used to remove the mother liquor? centrifuged and washed with about 15 parts of cold toluene * The yield of dry Glycerylguarjacolat feeträgt 28 _r 75 parts (about 72 "2 $ ö © r 5? heori _©? hezogen the singesetsstc guaiacol) ο The product BClimilst at 80-81 ⁰ C ₀

Example 2

In β ISS with a condenser and a water trap out · »rüstetes Res.ktionsgefäß an aqueous sodium = liydroxidlösung (126 parts (3 _P 15 mol) maoh ISS 4βΟ parts of water) and 2700 ml of toluene and 300 ml of n-butanol were charged, and the mixture is heated while passing nitrogen through it. Then, 372 parts (3 »0 mole) of guaiacol are added at 50 ⁰ C and the mixture is heated to 94-95 ⁰ C, a toluene-n-butanol-water azeotrope distilled off. The toluene and the n-butane oil are continuously returned to the reaction vessel, while 480 ml of water are collected in the trap. The mixture is cooled to a temperature slightly below the reflux temperature, whereupon 330 parts (2-99 mol) of glycerol chlorohydrin sugesetst be heated and refluxed like "Das

1 6 Si

BATH ORIGINAL

Residual water wird.unter continued heating over a period of 4 hours at a Gefaßtemperatur of about 105 ⁰ C removed the mixture is cooled to 5O ⁰ G ₉ with concentrated ChlorwasserstoffsHure acidified to a pH value of 1 ~ * \ * iederum azeotropically dried at 50 ⁰ G filtered.

The hot filtrate is combined with a solution, kept at room temperature, of about 64 parts of a second yield of glyceryl guaiacolate crystals from an earlier sowing in about 320 ml of a toluene-II-butanol mixture in a volume ratio of 90:10. The combined solutions are then stirred to about. 35 to 40 ⁰ G cooled »The crystallization continues without inoculation eiiio The temperature is maintained for about 30 minutes _? whereupon the mixture on ein®! temperature is cooled from about 5 to 1O ⁰ C "After etiva 30 minutes at di @ s © r Semporatur is dsr filtered crystal, and di © Krisfealla v / ground with 250 ml of cold toluene ge · = wash ο Ea;> 7 © rüen 509 part © dry SlvcorylgwBjaoolat erlmltesn This corresponds to a yield of about 85 fi exercises theories including the most returned white yields, the product has a melting point of ÜQ - En ⁰ G '

Ba? 3 F-Bfffahrsn according to the invention can also be used in the vo.rs.tshsnd © n examples τβ-rwendetsii? I-Bufeanol3 by a room from "Butanollaom © r © n gsfLilvrk warcUnu instead of dos in the Boiapielsn can also use oleoerinhromhydrin

■ J 0 -I s) 2 2/1! δ 9

Some preferred embodiments of the invention have been made ssur explanation given; however, there can be numerous Changes and modifications can be made without departing from the scope of the invention.

Claims

Jü9B22 / 11Stf

Claims (1)

2256508 PateataäsBiÜ eh e Throw out wtäz- production to & krietallinea ethers. a phenol r where R is a. Alkyl · = - or Älko & jreöt with 1 to 4 carbon atoms ₉ halogen © the phenyl radical and Y oxygen © cies? · Schwof ©! represents UM woria ia «s 0 to 5 ₉ a ™ 1 feie 3 and M = 5- & not greater than 6 are ₉ isjad an alkyl _{polyol 8} daaureh geke η η ι e ί o hi et, <aa aqueous SO sling A phenol yiss of an isasisclien alkali compound is dehydrated by azeotropic distillation with a mixture of a Eumoeyeligeken "benseliseliea solvent with 6 to 10 carbon atoms and" inem alkahol with 4 to 8 carbon atoms * v / ob © i the ratio between benzol in solvent and alkanol about 10s90 to about 90s10 is that the alkali phenolate obtained is reacted with a halohydrin at the reflux temperature of the mixture and that the ether is removed from the mixture obtained Method according to claim 1 _s characterized * that one © in phenol with a free and as polyol © in © n triol 30S812 / 1 π method according to claim 1 or 2, characterized in that a phenol with an alkoxy substituent with 1 to 4 carbon atoms is used » 4 »Method according to one of claims 1 to 3“ thereby characterized in that the benzene solvent is the main component of the mixture of benzene Represents solvent and alkenol. 5ο method according to claim 4 »characterized« that a hydrocarbon is used as the bengal solvent. 6ο method according to claim 4 »characterized in that that at least one compound from the group of n-butanol, sec-butanol and isobutanol is used as the alkanol. Process according to one of Claims 1 to S _9, characterized in that an oC- Hönoohlorhydrin and / or a ® £ monobromohydrin is used as the halohydrin 8ο method according to one of claims 1 to 7t thereby characterized »that guaiacol is used as the phenol and glycerol chlorohydrin as the halohydrin. 9 »Method according to claim 5, characterized in that that. the hydrocarbon used is toluene and the alkanol used is n-butanol. Oo method according to claim 9 t characterized that one adjusted the volume ratio between toluene and n-butanol to about 90t10 309822/1159