CA1112249A - Method for producing alkyl tetrahydrofurfurul ethers - Google Patents

Abstract

INVENTOR: HENRY R. NYCHKA
INVENTION: METHOD FOR PRODUCING ALKYL TETRAHYDROFURFURYL ETHERS

ABSTRACT OF THE DISCLOSURE

Tetrahydrofurfuryl ethers are produced by reacting tetra-hydrofurfuryl alcohol with an alkali hydroxide or alkaline earth oxide to produce an alkali or alkaline earth alkoxide salt, and reacting the alkoxide salt so produced with an alkyl halide, with the alkyl having 1-4 carbons, to produce the alkyl tetrahydrofur-furyl ether.

Description

sAcKGRouND OF THE I~VENTION
Ethers of tetrahydrofurfuryl alcohol (~H~A) having the structure ~ - Ct~ ~

are a known class of compounds. References disclosing their manufacture and use include U.S. Patents Nos. 2,040,898 (Zellhoefer), 2,153,135 (Dickey et al.), 2,247,482 (~ickey et al.), 2,993,915 (Luskin), 2,945,994 (Dazzi) and 3,668,134 (Làmberti et al.). Synthesis of several such ethers is also disclosed in W. R. Kirner, "Alpha-tetrahydrofurfuryl Chloride and Alpha-tetrahydrofurfuryl Ethers", Journal f_the American Chemical Societx, Vol. 52, pages 3251-3256 (1930).
Drior art methods have been of two types, the direct etherification type and the alkoxylate-etherification type.
Direct etherification, as disclosed by the Kirner article, involves reacting THFA and a halogenated species, generally an alkyl halide, with an alkali hydroxide or other base present.
For example, Kirner mixed THFA with an excess of methyl iodide, ethyl bromide, n-propyl bromide, n-butyl bromide or benzyl chloride. To this mixture, Kirner added pulverized potassium hydroxide in small portions (but eventually to a 100% excess) producing the alkyl tetrahydrofurfuryl ether, water and potassium halide. The same type of direct method was followed in U.S.
Patent 2,945,994. In U.S. Patent 2,247,482, the potassium hydroxide was first dissolved in T~IF~ and then the halogenated compound was added. The disclosure clearly indicates, however, that the base was provided only to neutralize mineral acid formed in the reaction between the alcohol and halogenated compound. Thus the reaction can be seen to be a direct etherification reaction.
Direct etherification reactions, while producing the desired ethers, also produce undesired by-products Erom the reac-tion of the halogenated reactant and the base, including alkanols, alkenes and alkyl alkyl ethers. When an excess of alkyl halide is used, so as to consume the available T~FA, the alkyl halide is not easily separated from the product in usa~le form ~or recycling.
Alko~ylate-etherification reactions have been proposed, as in U.S. Patent No. 3,668,134 wherein THFA was reacted with metallic sodium to produce an alkali alkoxylate salt of the formula '' 1 ~ CH2 Na The alkali alkoxylate salt was then reacted with n-pentyl bromide to produce n-pentyl tetrahydrofurfuryl ether. H. Feuer and J.
Hooz, "Methods of Formation of the Ether Linkage", in The Chemistry of the Ether Linkage by S. Patai ~Interscience Publications 1967) discloses at pages 446-47 under the heading "Nucleophilic Substi-tutions", subheading "Reactions of Alkoxides with Alkyl ~alidesl' the reaction R10 + R2X yields RlOR2 ~ X . This is generic to the second step of the alkoxide-etherification method. They state that various methods are employed to convert higher molecular weight alcohols into their salts, including the use of sodium hydride or sodium amide, reEluxing sodium or potassium (metal) in high boiling solvents with the mixture of alcohol and alkyl halide and employing sodium naphthalene.
Known alkoxylate-etheriEication methods suffer from the costs and dangers associated with using sodium or potasslum metal as a reactant. The quantitative ~ormation of gaseous hydrogen as z~ ~
a by-product in many of these reactions also poses ha~ards of flammability and pressurization. Organic sodium or potassium- con-taining reactants also pose cost and safety problems in that these compounds are generally formed from the metals and are themselves unstable.
BRIEF DESCRIPTION OF THE INVENTION
The invention includes a method of producing tetra-hydrofurfuryl ethers comprising the steps of reacting tetra-hydrofurfuryl alcohol with an alkali hydroxide or alkaline earth oxide at a temperature of at least about 120C to produce an alkali or alkaline earth alkoxide salt, and reacting the alkoxide salt so produced with an alkyl halide of the formula RX, where R is alkyl having 1-~ carbons and X is Cl, sr or I to produce the alkyl tetrahydrofurfuryl ether.
It is particularly surprising that such an alkoxide-etherification synthesis can occur with alkali hydroxide or alkaline earth oxide as one reactant in view of the prior belief that (1) the alkoxide formation form alcohols and hydroxides is generally quite reversible and hence not quantitative and

(2) that the water by-product of the formation of alkoxides from alcohols and hydroxides would have to be removed before adding alkyl halide to avoid hydrolysis of the alkyl halide.
In fact, it has been found that the yields of product ether and extent of formation of alcohol by-products are generally unaffected by the failure to remove water from the system.
Yields have been obtained which are substantially quantitative with respect to the THFA consumed and above 90% with respect to the alkyl halide consumed.
The molar ratio of alkyl halide to alkali hydroxide to THFA is 1 to about 1 to about 1.0-~Ø In two preferred forms, the above ratio is 1 to about 1 to about 2.0 ~.0 or is 1 to about 1 to 1.0-1.5. With such ratios, the alkyl halide is completely consumed and Eormation oE
by-products therefrom is minimized. In the ~irst of the preferred forms, the excess THFA serves as a solvent for the alkoxide and product ether (both of which are soluble therein).
THFA is quite stable so that it may be recycled. In the second of the preferred forms, little or no excess THFA as solvent is provided, with the alkoxide rnelt serving as the intermediate species, and a minimum, or no THFA need be recycled. Even with equal molar ratios of THFA and hydroxide, the formation of the alkoxide is almost quantitative, a surprising result for a reaction of a type previously considered reversible.
When using alkaline earth oxides to form the alkoxide, the molar ratio of alkyl halide to alkaline earth oxide to THFA
is 1 to about 0.5 to about 1.1-4.0, with the preferred ratio being 1 to about 0.5 to about 1.5-2.5, and the most preferred ratio being about 1:0.5:2Ø
DETAILED DESCRIPTION OF THE INVENTION
_____ __ ___ ___ ___ _ It should be appreciated that a molar proportion of hydroxide about equal to the molar proportion of alkyl halide will assure that the proper amount of alkoxide will be formed to consume the alkyl halide and form products therefrom. Too much hydroxide will form an excess of alkoxide which can form undesired by-products (thus wasting THFA). Too little hydroxide will leave some alkyl halide unreacted, thus causing it to form undesired by-products, such as alcohols (thus wasting the alkyl halide). Somewhat more or less hydroxide than equal molar amounts (or somewhat less oxide than one-half molar amounts) can be used, but is less preferred because of the loss of THFA
or alkyl halide that results.
It is within the scope of the present invention to have inert materials such as inert solvents present during one or both of the alkoxide forrnation step and the etllerification step. None-theless, it is preferred to have only the reactants, sometimes including an excess of THFA, in the alkoxide formation step, thus having the reaction mixture consist of THFA and alkali hydroxide or alkaline earth oxide. It is also pre~erred to have only reac-tants (alkoxide and alkyl halide) present in the etherification step, with wa~er by-product and, sometimes, excess or solvent THFA
also present~
The reactants for the alkoxide formation step include THFA (sometimes with minor amounts of impurities such as ~ = CH2 or ~ - CH2CH2CHOHCH3 and an alkali hydroxide or alkaline earth oxide. While LiOH, NaOH, KOH, RbOH, FrOH, CsOH seo, MgO, CaO and BaO could conceivably each be used, the preferred reactants are CaO, MgO, NaOH, KOH, LiOH and mixtures thereof, with NaOH and KOH being more preferred.
The preferred alkyl halide reactants are of the formula RX where R is alkyl having 1-4 carbons and preferably 2-4 carbons, with R as ethyl or n-butyl being more preferred~ X is Cl, Br or I, with Cl being preferred. With the preferred alkyl chlorides, the ultimate salt by-product is a chloride salt (such as RCl or NaCl) which may be more easily disposed of then some bromide or iodide salts.
In some preferred forms, the reaction mixture for pre-paring the alkali or alkaline earth alkoxide salt consists of THFA
and the alkali hydroxide or alkaline earth oxide~ Hence no solvent except excess THFA is present. In some preferred forms, the pro-duct of the reactiGn between THFA and the alkali hydroxide or alkaline earth oxide is directly reacted with the alkyl halide.
Hence no water removal or other intermediate purification step is required. In some forms of the invention, however, water is removed before addition of alkyl halide by simple or azeotropic distillation. This may simpli~y ultima~e recovery of product.
In some preferred forms, the alkali or alkaline earth alkoxide salt is reacted with the ethyl halide at an autogenous pressure up ~o about 110 psig, pre~erably up to about 60 psig. In some preferred forms, after the second reaction, by-product alkali or alkaline earth halide is removed by filtration and the filtrate is distilled into a water and alkyl tetrahydrofurfuryl ether frac-tion and an excess THFA fraction. With R as ethyl, the water and alkyl tetrahydrofurfuryl ether fraction includes substantially the azeotrope containing about 76 weight percent water and about 24 weight percent ethyl tetrahydrofurfuryl ether (ETFE).
In general, a temperature of at least about 120C is re-quired for reaction between THFA and the base. In some preferred forms of the invention, alkali hydroxide pellets and THFA are heated to about 120-160C, the reaction mixture is cooled to about 70-110C and the alkyl halide is then added. Similar reaction con-ditions can be used with alkaline earth oxides.
So that there will be no question about the structure of reactants, intermediates and products of the present reaction sequence, the reactant THFA is:

~ 2 !

the reactant hydroxide or oxide is MOH or MO (the latter if M is an alkaline earth metal), the reactant alkyl halide is ~X, the intermediate is one or a mixture of the Eollowing:

z~

- - j ~--~H2 M ~ /--C~12~ ~ C~2MH
. .... 7 ~C~ - CH20MOC~2--.,~ ~

with the first drawn structure being the intermediate when M is an alkali metal and the others being possible structures when M is an alkaline earth metal (depending on which alkaline earth metal and on the proportion used).
Example 1 The apparatus consisted of a one liter 3-neck flask equipped with a gas inlet, a stirrer and thermometer. To the flask a dry ice condenser followed by a liquid nitrogen cooled trap was attached. The purpose of the trap was to condense any by-product C2H4 present in the system which was under a constant helium purge during the experiment.
A slurry of 40~.0 gram (4.00 mols or m) THFA and 56.2 grams (1.36 mols~ NaOH was heated with stirring, to 150 at which point the NaO~ pellets dissolved to give a clear yellow solution.
The solution was cooled to 87 and 66.5 grams (1.03 mols) of C2H5Cl was introduced over a one hour period. During this time the unreacted C2H5Cl refluxed gently until it was finally consumed.
The mixture which was now a heavy but stirrable slurry was fil-tered by vacuum suction. After washing the NaCl filter cake with fresh THFA, it was removed, dried and analyzed for Cl . Prior to distillation, tbe combined filtrate and washing was analyzed by gas chromatography. The chromatography data plus the ethylene collected formed the basis for yields reported in Table I.

Examples 2-4 Example 1 was repeated with variations in mol ratio, temperature and base as shown in Table I, with the yield of ETFE
and % byproducts also as shown in Table I.
Table I
Etherification at Atmospheric Pressure Example 1 2 3 4 C2H5Cl (m) 1.03 0.99 0.87 0.91 THFA (M) 4.00 2.00 1.00 4.00 Base (m) 1.36 1.00 1.00 1.36 (NaOH) (NaOH) (NaOH) (KOH) Reaction Temp. 87 100 135 85 ( o C ) Running time (hrs~) 1.0 1.0 2.0 1.2 ~C2H5Cl Con. 9~ 93 81 % ETFE Yld~* 95 89 34 93 % 2 4 2 S 10 3 ~C2H5OH Yld. 3 6 6 4 *Based on C2H5Cl consumed. % ETFE yield based on THFA consumed was essentially quantitative~
Examples 5-9 Examples 5, 6, 7 and 8 represent the preparation of ETFE
under superatmospheric pressure. All examples were prepared in a similar manner with the reaction amounts and conditions and the results shown in Table II~ A description of example 6 follows:
20.6 grams (0.50 m) of NaOH pellets were dissolved in 204 grams (2.00m) THFA by heating to about 150 with stirring, the solution was charged to a 700 mJ. Fisher-Porter Pres~ure Bottle (equipped with magnetic stirring, a pressure gauge and inlet line) which was cooled in a dry ice/acetone bath and evacuated. 36 grams (0.56m) of ethyl chloride were conden~ed in after which the reactor was allowed to reach room temperature and then immersed in an oil bath at 100~ In ten minutes the pressure increased ~rom a Eew pounds initially to 45 psig maximum. After the next ten minutes the pressure dropped ~o 22 psig. The -final pressure after 60 minutes (total) was 13 psig. This was due mostly to C2H~ forma-tion. At room temperature the pressure was sligh~ly less than atmospheric. A conservative estimate o~ C2H4 formation, which was based on assuming the C2~4 occupied the free volume in the reactor, was 0.02m. The amount of ethyl alcohol, the other side product, was determined by gas chromatography (G.C.) and also found to be 0.02m. Analysis of the reaction mixture showed m Cl , which was equal to 96~ conversion of C2H5Cl on the basis of NaOH applied.
The yield of ETFE was 92% on the basis of C2H5Cl consumed. A
direct determination of ETFE yield by gas chromatography analysis and using standard response factor correckions gave a confirming value which was very close to 100%.
Table II
Etherification at Superatmospheric Pressure Using 0~50 mols of C2H5Cl Example 5 6 7 8 9 EtCl (m) .45 .56 .61 L 57 .56 THFA (m) 1.93 2.00 2.00 2.00 2.00 NaOH (m) .52 .50 .50 .50 KOH ~50 C/h. 55/1.5 100/l 150/l 125/l 125/l psig Max. 8 45 56 33 30 % conv. C2H5Cl 40 96 98 96 98 ~ Yield ETFEE_ 92 92 93 94 - A - Does not include 30 minutes heat-up time B - 10 minute heat-up time C - Essentially no heat-up time.
D - Conversion of C2H5Cl to Cl based on NaOH applied.
E - Molar % of ETFE formed by Cl formed.

_g_ Example 10 A clear yellow slurry was prepared as in Example 1 from 173 grams (4.20 m.) of NaOH and 857 grams (8.40 m.) of ~HFA. The solution was cooled to 100 and 268 grams (~.17 m~ of C2H5Cl wa5 introduced over a 4 hour period during which time the unreacted C~H5Cl refluxed. ~he reaction was held on temperature for one hour more to maximize the conversion of C2H5Cl~ The mixture, which was now a heavy but stirrable slurry, was cooled and filtered by vacuum suction. The NaCl was washed in the filtering funnel with 102 g. of fresh THFA. The main filtrate and washings were charged to a 42" vacuum jacketed, silver mirrored column packed with gla~s helices. The distillation results for a 1108 gram charge are reported in Table III and the yield data in Table IV.
Table III
Fr action b.p.wt. g. Remarks 1. Azeotrope 85-95 103 76~/24% H2O/ETFE
2. Intermediate 95-142 1.3

3. Main 142-165 609 75% ETFE/25~ T~FA by G.C.

4. Bottoms 342 2% ETFE/98~ THFA by G.C.
5O Back-up Trap - 11 Low boiler C2H5Cl 20 6. Loss2 42 Handling Not~ 1 The azeotropic mixture which contained some ethanol was redistilled. A purified sample of 78.7g., containing 76~ H2O by Karl Fisher analysis, was shaken with small amounts of NaCl (18.6g.) until the upper ETFE layer no longer increased.
Note 2 A 53% recovery of ET~E was obtained. 42 grams oE
material were lost in distillation. Additional losse~ included 42 grams in filtration and 22 gram~ in drying the NaCl.
The liquid N2 trap contained 7g. of condensed C2H4. These losses amounted to 7 to 10% of the total material being processed.

2~

The bottoms fraction o~ THFA was recycled three times.
Each time ~he fraction was combined with sufficient ~resh rrHF~ and reacted with NaOH as described in Example 10. The quantities of reactants used were essentially the same as in Example 10~
The separation of ETFE from THFA proved difficult in a 42" helix packed column. This meant that the hear~ cut which usually contained only about 75~ ETFE had to be analyzed by gas chromatography to obtain yield data. The recovery of high purity ETFE, however, is not a problem in larger scale distillations which were conducted in a longer column at a high reflux ratio.
In Table IV it is seen that in the third recycle experi-ment the yield of distilled ETFE decreased to 70%. There is some question, however, as to the accuracy of this number since a gas chromatography analysis of the total reaction mixture before dis-tillation suggested a yield of 87%~
It appears that T~FA can be recycled ~or a few times.
Eventually it may require distillation if it becomes progressively darker with continued use.
Table IV

% Con. C2H ~ % Yld.** ~Yld.***
ETFE
Example C2H ~ C2~4 (Diff.) ETFE
10 Initial 86 8 7 85 100 11 1st recycle 90 7 7 86 89 12 2nd recycle 93 7 6 87 88 13 3rd recycle 80 7 6 87 70 * mm C2H5Cl in~ X 100 m C2H5OH (GC) ** - X 100 m Cl-m Cl X 100 (C2H4 trapped in liquid N2) **~ Yield based on distillation: m F~TFE Recovered m Cl-Example 14 1089 pounds (10.68 pound moles) of THF~ were reactedwith 220 pounds (5.34 pound moles) of NaOH. After reaction, 125 lbs. of unreac~ed THFA and water by-product were distilled off.
379 pounds (5.88 pound moles) o~ ethyl chloride were then added.
After reaction 981 pounds of crude product were separated by fil-tration from 500 pounds of solids (containing by-product NaCl and residual organics). About 82 pounds of the 1688 total pounds charged are unaccounted for. By distillation, 350 pounds (2.69 mole pounds) of ethyl tetrahydrofurfuryl ether (ETFE) were recovered from the crude product. This represents about 25~
yield based on THFA charged, about 50% yield based on NaOH charged (the limiting reagent) or about 46~ based on ethyl chloride charged.
Example 15 1165 pounds (11.42 pound moles) of THFA were reacted with 480 pounds (11.64 pound moles) of NaOH. After reaction was com-pleted, 652 pounds (10.11 pound moles) of ethyl chloride were added.
After reaction was completed, 1700 pounds of water were added form-ing an aqueous phase and an organic phase. Water was added untilall of the salt had dissolved. 1343 pounds of crude product (the organic phase) were decanted off leaving an aqueous phase of 2533 pounds (later separated into 56 pounds of organics and 2477 pounds of salts and water). About 700 pounds (5.38 mole pounds) of ETFE
were recovered from the crude product, representing a yield of 47%
based on THFA charged, 46% based on NaOH cnarged and 53% based on ethyl chloride charged (the limiting reagent)~ ~bout 121 pounds of the 3997 pounds charged (including water) are unaccounted for.
It will be appreclated that unreacted THE~ can be recov-ered from the first distillate in Bxample 14 or from the crudeproduct in Example 15 and recycled, a~ in Exarnples 11-13.

Example 16 A satisfactory yield of the n-butyl ether, b.p. 195C, is also obtained by conducting the etherification at atmospheric pressure and following the procedure described for example 1 ex-cept for the replacement of ethyl chloride with n-butyl chloride~
Examples 17-20 Satisfactory yields of the n~propyl, methyl, i-butyl and i-propyl ethers are obtained according to the procedure of Example 1 with ethyl chloride replaced by n-propyl bromide, methyl iodide, i-butyl bromide and i-propyl chloride.

~0

Claims (17)

What is claimed is:

1. A method of producing tetrahydrofurfuryl ethers comprising the steps:
reacting tetrahydrofurfuryl alcohol with an alkali hydroxide or alkaline earth oxide at a temperature of at least about 120°C to produce an alkali or alkaline earth alkoxide salt, and reacting the alkali or alkaline earth alkoxide salt so produced with an alkyl halide of the formula RX, where R
is alkyl having 1-4 carbons and X is Cl, Br or I to produce the alkyl tetrahydrofurfuryl ether;
wherein, if the alkali hydroxide is used, then the molar ratio of alkyl halide to alkali hydroxide to tetrahydro-furfuryl alcohol is 1 to about 1.0 to about 1.0-4.0 and, wherein, if the alkaline earth oxide is used, then the molar ratio of alkyl halide to alkaline earth oxide to tetrahydrofurfuryl alcohol is 1 to about 0.5 to about 1-4Ø

2. The method of claim 1 wherein X is Cl.

3. The method of claim 1 wherein R is alkyl having 2-4 carbons.

4. The method of claim 3 wherein R is ethyl.

5. The method of claim 3 wherein R is n-butyl.

6. The method of claim 1 wherein the alkali hydroxide is selected from KOH, NaOH and mixtures thereof.

7. The method of claim 1 wherein the alkali or alka-line earth alkoxide salt is prepared from a reaction mixture consisting of tetrahydrofurfuryl alcohol and the alkali hydroxide or alkaline earth oxide.

8. The method of claim 1 wherein the product of the reaction between tetrahydrofurfuryl alcohol and the alkali hydroxide or alkaline earth oxide is directly reacted with the alkyl halide.

9. The method of claim 1 wherein the alkali or alkaline earth alkoxide salt is reacted with the alkyl halide at an autogenous pressure up to about 110 psig.

10. The method of claim 9 wherein the autogenous pressure is up to 60 psig.

11. The method of claim 1 wherein said alkali hydroxide is used and said ratio is 1 to about 1 to about 2.0-4Ø

12. The method of claim 1 wherein said alkali hydroxide is used and said ratio is 1 to about 1 to about 1.0-1.5.

13. The method of claim 1 wherein alkali hydroxide pellets and tetrahydrofurfuryl alcohol are heated to about 12D-160°C and the alkyl halide is then added.

14. The method of claim 1 wherein the molar ratio of alkyl halide to alkaline earth oxide to tetrahydrofurfuryl alcohol is 1 to about 0.5 to about 1.5-2.5.

15. The method of claim 1 wherein alkali hydroxide pellets and tetrahydrofurfuryl alcohol are heated to about 120-160°C, the reaction mixture is cooled to about 70-110°C.
and the alkyl halide is then added.

16. The method of claim 1 wherein by-product alkali or alkaline earth halide is removed by filtration and the filtrate is distilled into a water and alkyl tetrahydrofurfuryl ether fraction and an excess tetrahydrofurfuryl alcohol fraction.

17. The method of claim 16 wherein R is ethyl and said water and alkyl tetrahydrofurfuryl ether fraction includes substantially the azeotrope containing about 76 weight percent water and about 24 weight percent ethyl tetrahydrofurfuryl ether.