US2493676A - Pseudo esters of levulinic acid - Google Patents

Description

Patented Jan. 3, 1950 PSEUDO ESTERS OF LEVULINIC ACID David P. Langlois and Hans Wolff, Decatur, Ill.,

assignors to A. E. Staley Manufacturing Company, Decatur, 111., a corporation of Delaware No Drawing. Application July 21, 1947, Serial No. 762,528

This invention relates to novel pseudo esters of gamma keto carboxylic acids. More particularly, it relates to the pseudo esters of saturated aliphatic gamma keto carboxylic acids, such as, for example, levulinic acid, and to methods for the preparation of these new chemical compounds, and the provision of such a process and the recovery of such products is a principal object of the invention.

Other objects of the invention will in part be obvious and will in part appear hereinafter.

The invention accordingly comprises the several steps and the relation of one or more of such steps with respect to each of the others thereof, which will be exemplified in the process hereinafter disclosed, and the scope of the application of which will be indicated in the claims.

By the expression pseudo ester is meant a compound that (1) is isomeric with a normal ester, (2) has properties unlike those of the normal ester, (3) yields the same acid and alcohol as the normal ester does when hydrolyzed, and (4) in general, can be isomerized to the normal ester.

Pseudo esters of aromatic gamma keto acids are described in the chemical literature. Reference is made to pages 445-447 of volume 56 (1934) of the Journal of the American Chemical Society for the pseudo 'methyl and ethyl esters of a p-bromobenzoyl acrylic acid, and to pages 1537- 1541 of volume 63 (1941) of the same journal for the pseudo methyl esters of substituted benzoyl benzoic acids. Evidence is presented in both of these publications to show that the described pseudo esters may be regarded as lactones of hypothetical gamma hemiketol acids, and have the indicated common five membered ring structureI I wherein R1 and R2 are alkyl or aryl groups.

The double bond between the 3 and 4 carbon 9 Claims. (Cl. 260344) 2 atoms is fixed in the acrylic acid pseudo esters; in the pseudo esters of the benzoyl benzoic acids, the double bond presumably alternates with a single bond because the carbon atoms are in the benzene ring.

We have discovered that pseudo esters of levulinic acid, none of which have hitherto been reported, can be prepared by the catalytic addition of alcohols to alpha angelica lactone, which is generally regarded as having the indicated structure II The new compounds thus obtained areformed by the addition of the alcohol (ROH) to the carbon-carbon double bond to yield structures of type III.

wherein R is a hydrocarbon radical selected from the group consisting of alkyl, aryl, and aralkyl radicals.

It will be noted that structure III may be regarded as a lactone of a hypothetical gamma hemiketol acid, and that its ring system is'the same as that of the pseudo esters of the gamma keto acids mentioned above, except for the single bond between the 3 and 4 carbon atoms in place of a fixed or alternating double bond.

In support of this structure of the pseudo esters of levulinic acid, the following should be considered: (1) That the catalytic addition of alcohols to the aliphatic carbon-carbon double bond, though not a well-known reaction, is not an implausible one; (2) the ring structure is essentially the same as that fairly well established for the pseudo esters of other gamma keto carboxylic acids; (3) the calculated molecular refractions oi the pseudo esters, based on the Auwers'and Eisenlohr constants and the present ring structure, agree with the observed values; and (4) if 3 the acid'chloride of levulinic acid, obtained by treating the acid with thionyl chloride, and which probably has structure IV,

is reacted cold with an alcohol under conditions that prevent rapid isomerization of pseudo ester to the normal form, there is obtained a pseudo ester that is identical in its physical and chemical properties with the pseudo ester obtained by catalytic reaction of the same alcohol with alpha angelica lactone in accordance with our invention.

Reference is made to page 1751 of volume 2 of the secend eclition @1943) of Gilmanis --..@rganic Chemistry, publ-ished Roy J 01m Wiley 1386 ESons. for a discussion of the Auwers and Eisenloh constants mentioned above.

The pseudo esters of levulinic acid are chiefly distinguished from the normal-esters-b ythe'ex treme ease with which theyrmay. be.--sapomtierl. In fact they saponify so readily, nsconyparedswith the normal forms, that the proportlomofcfipsendo ester in a neutral mixture of bth ty.pes.can be rapidly and accurately determined by coldltitnation of the mixture with standard alkali solution.

The physical properties of the pseudo estersdilier from those of the corresponding normal esters 4 chloride for example, are preferred because of the ease with which they may be removed from the reacted mixture.

The acid catalysts that promote the addition of alcohols to alpha angelica lactone also accelerate the isomerization of the formed pseudo ester to the normal ester. The pure pseudo esters can be rearranged quantitively to the normal forms by the action of the acidic catalysts. This isomerization is quite slow at room temperature with traces of the catalysts, requiring weeks for completion, but becomes progressively more rapid as the temperature and catalyst concentration are increased. For example, complete isomerization of pseudo to normal ester can be accomplished by heating the ester with the corresponding alcohol .ioraaboutaonethour atlaheutlldo 0.; in the presrence of about 1?% hydrogen chloride. iUnder a given set of conditions, however, the rate of iso- Lmerization appears always to be less than the 7 rate of formation of the pseudo ester.

.9%therpseudosester during the reaction period.

These concentrations will vary, depending upon *theparticular-alcohol and catalyst used. Table 1*i'lluStrates the relationship between kind of a1- coholzand near-optimum catalysts concentration 00 when hydrogen chloride is the catalyst.

-fCablell J a V N =:HC1 in Y-ieldlof-' 5PSQ11d0 a 4 flms. of- -Gmsnof Clans. of

Kind of Alcohol Reaction otal Ester 1n Alcohol tMixture "Esters 5 )TotaFEsters 3 i mderiamti ERerE'ent Rerflent c0, ,127.-.5 .loioos 013 to 90 20 "27} 5 0. (I40 0. 084 92 '90 20 27. 5 0. 025 0. 05% 1'90 :62 f 27: 5 0.3m} ell- 63 .,-98 95 28 27; 5 02300 0. 54 92 ..98 28 $2755 03300 11054 3 95 C295 28 .21:5 ,0.025 r 0. (145 s 68 28 "273 5 U. 038 01069 90 $2755 412025. .202 0215 392 3:66 .25 #26 D. 010 0. A60 1,00

and the differences are fairly consistent; The boiling points of the pseudo esters -are -either ab-out the 'same 'cr s'lightly highei than' those of the normal esters, and the densities and refractive "indices of the former are consistently somewhat higher than those' of the latter.

The pseudo esters of levulinic acid will find many uses in the solvents field- In particular,

tc'yclohexyl; pseudo ;levulinate"'has very powerful fExamplesot these arefhydrogen chloridejhydro- ,sen; bromide. sulfuric..acid, phosphoric, acid. arosmatichsulfonicrabids, andmonothlfiacetiaabid. Zmgener'al, any; strong acid appreciably. Solfiblegin the reaction .mixturel-is satisfactory.foiithis, purpose. lThe volatile .cataly'stsesufchlas. hydrogen 575 The "following .proce'dure :for preparing the pseudo esters of levulinic acid'from alpha. angeb ica lactone and alcohols. is applicable: to the alcohols in general except for methyl, ,ethyl, anid .ngzpropyl alcohol. "Catalyst is tdissolved in the selected alcohol .until the .latterycontains about Idouble the concentration'of catalystthatfis desired in the reaction mixture of alcohol and alpha angelica lactone. An excess of the alcohol containing the catalystsisthen addedtca givenvol- ..ume .of.the. angelica' lactone atroom temperature. For example, this maybe about an equal volume of isopropyl andlthe butylalcohols, and about one and.one-half.-volumes of the higher alcohols, up .to andincludingthose containing eight carbon .atoms. jThe mixture is allowed to. stand. The reaction is'stronglyexothermic. Even when'the reactionmixture is held in uninsulate'dglass flasks, andiitsvolume is only. ab0ut"5O 1 211., its tempera-- ture may rise to about 60. to 80C. over aperiodof about two" hours; and then drop to'room tempera- 'ture-in-about-an equal period *oftime. :Good yields of the pseudo esters are obtained when the catalyst concentration is so adjusted that the foregoing rate and extent of temperature change occurs spontaneously. ZToo-mu'ch catalyst, causing a more rapidrise in temperature, or too little catalyst, whichcausesthe. temperature. rise to, lag, resultsin' reduced ,yieIdsOf, pseudoester. ,About four hours after mixing the reactants together the catalyst is either removed from the reaction mixture or inactivated. If it is a volatile one, such cold with tenth normal aqueous sodium hydroxide solution, using phenol-phthalein as indicator, to determine the proportion of pseudo ester presas hydrogen chloride, it may conveniently be reent. The remainder is assumed to be normal moved from the reaction mixture by passing a ester. The'mixed esters are diluted with an equal stream of dry air through the latter. If it is a volume of the corresponding alcohol. Seminon-volatile one, such as toluene sulfonic acid, carbazide hydrochloride in amount slightly in it is preferably neutralized and inactivated by excess of that required to combine with all of shaking the reaction mixture with solid'sodium, the normal ester and an equal weight of finely carbonate. The reaction mixture, either freed of powdered potassium acetate are added to the volatile catalyst by aeration, or neutralized with I- alcohol-ester mixture, which is allowed to stand a weak base such as sodium carbonate to inactiwith intermittent shaking for about one day at vate the catalyst, and filtered to remove solids, is i room temperature. The mixture is then diluted then fractionally distilled under reduced pressure. a with diethyl ether, allowed to stand for about one The pseudo ester mixed with some normal ester hour to permit complete precipitation of ether is collected over a boiling point range of. about insoluble materials, and then filtered. The fil- 2 C. I- trate is fractionally distilled under reduced pres- To obtain substantial yields of the pseudo esters sure, and pure pseudo ester, which has a higher from methyl, ethyl, and n-propyl alcohol, it is boiling point than either the alcohol or ether, is n s y to modify the f re ing pro edur collected over a boiling point range of about 2C. One satisfactory way of doing this is as follows: Purity of a pseudo ester of levulinic acid may h The alpha angelica lactone is diluted with at be determined from its saponiflcation number, least'two volumes of diethyl ether, and preferably cold titre, and constancy of boiling point. Cold three or four, before the alcohol and catalyst are titre and saponification number are conveniently added to it. The mixture is allowed to stand un- 2;; determined by first mixing a weighed sample of der a reflux condenser until the reaction is comthe ester withra small volume of distilledwater plete, which preferably requires'about four hours. and titrating the mixture at room temperature No external heating is required. The mixed with tenth normal aqueous sodium hydroxide esters may then be separated from the catalyst, solution, using phenolphthalein indicator. When diluent, and unreacted materials as described in 3Q the'pink colorend point first perists for about one the preceding paragraph. 7 -minute, the titre is ready. More tenth normal Table 2 lists the operating conditions and prodalkali solution'is added until there is present an uct yieldsin making the lower pseudo esters by excess of about 10%, based on the calculated the dilution method. normal ester'present. The mixture is then re- Table No. 2

. Yield'ot Pseudo rats; as as are. 5,333; I 7 Percent Pei-cent methyl 100 25 o. 100 92 ethyl 25 100 25 0.050 90 n-propyl 25 100 25 050 92 38 Increased yields of pseudo esters from primary 4 fluxed for one hour, acidified with a measured alcohols in general may be obtained by diluting excess of tenth normal sulfuric acid, boiled gently the reaction mixture with a nonreactive low boilfor about two minutes to expel carbon dioxide, ing liquid such as diethyl ether. Also, the use then quickly cooled and back titrated with tenth of such diluent with any alcohol is an added adnormal sodium hydroxide. The saponification. vantage in the large scale preparation of the 50 number'is calculated from the total alkali conpseudo esters because it suitably controls the resumed during both cold and hot saponifications. action temperature. If catalytic addition of the If the correct saponification number is obtained alcohol to alpha angelica lactone on a large scale for a given ester, then the ratio of cold titre to is not carried out under a reflux condenser in the total titre is taken as the proportion of pseudo presence of a relatively low boiling diluent, some ester present. other means of preventing overheating of the The addition of organic hydroxy compounds to reaction mixture must be used. alpha angelica lactone to yield pseudo esters of Separation of a pseudo ester of levulinic acid levulinic acid appears to be a general one for all from its mixture with the corresponding normal such compounds that will yield normal esters of ester cannot easily be accomplished by fractional 60 levulinic acid by a conventional method of pree distillation because the boiling points of the two paring esters. This includes primary and secforms are so close together. Separation of one ondary alcohols, whether monohydroxy or polyform from another in a mixture of the two can hydroxy, and whether aliphatic or aromatic. It be efi'ected, however, by taking advantage of the has been observed that. the secondary alcohols, fact that the normal ester has a carbonyl group 5 such as isopropyl alcohol, cyclohexanol, and whereas the pseudo ester does not. Reaction of phenol, together with such reactive primary althe mixture with a "carbonyl reagent such as cohols such as allyl alcohol and benzyl alcohol, semicarbazide, or phenylhydrazine, preferably form pseudo esters with alpha angelica lactone the former, affects only the normal ester, conmore readily than do the ordinary primary alverting it into a derivative which can be sepacohols. TableNo. 3 lists some physical properrated from the pseudo ester because of a distinct difference. in solubility or boiling point. The followingprocedure, using semicarbazide, is frequently successful.

- A weighed sample of the mixed esters is titrated ties of a number of pseudo esters prepared in this way. Properties of most of the corresponding normal esters are'included for comparison. All of-the listed esters were found to have the correct .saponiflcation numbers.

i H 4 Molec- Refrao- 'Reiractive v Dens1ty ular tion I wlndex: -Obs Oalc'd s9=91'G.=@= 1.0495 4 31. 52 31.57 90 92 0.@--' 1.1071 30.90 v 30.93 isoprppyl 103-105? C. @j 0. 9842 40.80 40.81 isopiop'yl p 103 105 C. 1.0151 40. 22 40.16 n-bHtYl-(n): 112-114? 9; 0, 9735- 45. 59 45. 42. 11-601 1 113-1 15? C.'@ 0. 9035 I 44.30 V 44.79 113-115 0. 0.9670 45.51 45.42 x 113e115?.Q.;@ 1;0108 44:50. 44.79-

105-10320. (Q 1.0277 40. 03 40. 34 106-108-G.: 1; 0677' 39. 46 "39. 70 124-126? 0.. 0.9828 2 53. 56 54.02 1 120121,C.@ 1.0013 49.30 49. 40 140-142 C. 1. 0308 52. 43 52. 46 140-143 0.-@ 1.0632 51.56 51.82 i33135 C..@ 1.1190 50. 97 51. 07 1 I30 13 :'G.:@ 1.1457 50.34 50.34

"Mahld' at "C. relative to" water'atli following examples W111 illustrate in the orde given (1)? the preparation or. pseuae esters of lviflinic acidfroin 'theiacid chlqrideftgljth (ii on or alcohols to .alpha" angelica lac e, .(3); the use of semicarba'zide' to efiect a Seafatibli of pseudo, from normal levulifiic ,acid'. s'ter and (4) isonirizatidii; or molecular rearrangement of the" pseudoestrifito'fis normal form;

' Efi'udmpZe-Zfseat:- 'mmg ef: thi'di'iyl chlorid dr'dpwise to 50 grains 'bflevulinic acldcontainedi in. a 200 ml. glass flask at such a rate that the temperature of thereaction mixture did not exceed 50 C. About one-half hour was required-- for the addition. The reaction mixture was th' held at about 50 C. under a reduced pressure of about 30 mm; of mercury to remove hydrogen chloride, sulfur dioxide, and excess thionyl ch10 ride. The crude levulinyl chloride thus obtained was added slowly to a vigorously stirred mixture e'of p toluene sulforiic'acid to catalyse he ad the iieutralizedreaction mixture was was mum to be.75%jpseudofester .f

of 125 m1. of methanol and grams offihel'y was fractionally distilled at 15 mlnJ-presstue;

There wasthusobtaind in 62% "yield' 'a fraction Boilingat 90'-92' C.-which was 92 pseudo estate The ethyl; allyl, and n-propyl esters were'also prepared in'similar fashion. In all three 'ofzthese' latter preparationsthe yield of mixed. esters were lowy'bein'g only'25 to" 30% bas'ed"on the levulini'c acid-takembu't the;proportions of pseudo esters present ranged from 90' to"92'% Eztamplefz v 1 One gram of p-tolue'ne sulfonicacid" was dissolved in 251111. of allyl alcohol; and-tothis-s'olution at room temperature'was' added? 25 m1: of alpha angelica lactone. temperature 05' the mixtureros'e slowly'to a maximu'mbf about 80C. over a periodof about two hours andthen dropped to room-temperature-in;-about-rafi equaltlme. The catalyst-in theieaction mixture was"- carefully neutralized with an equivalent amount of sodiummethylate dissolvd-ain allylva'lcohoh' Example? j- For y ams of ed 't in d if 'b i iiil Ii -J d mixdi' ud o' 'i p. 3 esters'of levulinic maw'as dilute, with50 mllof allyl alcohol and then mixedwitli'15 eianiseacfi of powdered semicarbaz'ide hydrochloride and po- "tassium acetatea This mixture was allowed to stand {with intermittent shaking for one day, thefi t waszunute'a with 10021711501 ether, filtered .idll im s l l p du t cl ding. t ecr stalline semicarbazone of normal allyl levulinate,

and 'fra-ctionally distilled undervacuum. After I and'allyl alcohol were removed??? g'ramsfof ure pseudo allyl ester was c-csneetea'at lOi isSTii'ovr tli'looilirig point range of 1063:1089 Cr This product had a"-co1d"- saponification-humber-of 160,- a density'of 1.067%317'20 C;-'-(refer"red to'water at 4 C.) and a refractive index of 1.4525 at 20 C. r

' v. V Ezticmple 4 f V V Fifty grams of pure pseudo methyllevulinate was diluted with .100 ml. of methanol contain in; 1 gram of hydrogen chloride, and the, result-. ing-solution was refluxed for one hour at atmos=i* pheri-c pressure.- Atthe end of this time the cold alkalttitre'of the mixture was equal to the 11y: drcgen chloride present." Fractional distillation ofthe mixture' at 15 mm.- pressure yielded-47 grams of pure normal methyl levulinateboiling' at 89==91 C. The recovered ester had no'appre ciable cold alkali titre, a sapomficationiiuiiiber of==;;a density-of 1.0495at 20 C.. and a re' fractiveindex of 1.4225 at 20 C.' Since "certain: changes may be madefin carry- 9 eral formula R-OH, wherein R. is a hydrocarbon radical selected from the group consisting of alkyl, aryl, and aralkyl radicals.

2. A process according to claim 1 in which the catalyst used is hydrogen chloride.

3. A process according to claim 1 in which the catalyst used is p-toluene sulphonic acid.

4. In the process of separating a pseudo ester of levulinic acid from a mixture of said ester with the corresponding normal ester, the improvement which comprises reacting said mixture with a carbonyl reagent selected from the group consisting of semicarbazide and phenylhydrazine.

5. The process of forming a pseudo ester of levulinic acid which comprises reacting alpha angelica lactone, in the presence of hydrogen chloride and at least two volumes of diethyl ether based on the alpha angelica lactone, with an organic hydroxy compound of the general formula ROH, wherein R is a hydrocarbon radical selected from the group consisting of alkyl, aryl, and aralkyl radicals.

6. Pseudo esters of levulinic acid having the structure where R is a hydrocarbon radical selected from the group consisting of alkyl, aryl and aralkyl 30 10 '7. The pseudo allyl ester of levulinic acid having the structure HgC-CH3 0:0 /C GHa 8. The pseudo cyclohexyl ester of levulinic acid having the structure 9. The pseudo phenyl ester of levulinic acid having the structure The following references are of record in the file of this patent:

UNITED STATES PATENTS Name Date Kyrides Jan. 30, 1945 OTHER' REFERENCES Bredt, Annalen der Chemie, Bd. 256, 1890,

Number 35 pages 314-16; 325, 326.

Claims (1)

1. 8. THE PSEUDO CYCLOHEXYL ESTER OF LEVULINIC ACID HAVING THE STRUCTURE