Note: Descriptions are shown in the official language in which they were submitted.
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
--2--
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
--3-
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
--5--
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.
--7--
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.
--10--
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-
2 4
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.
-12-
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
-13-
