INDUSTRIAL AND ENGINEERING CHEMISTRY
216
Hina, A., hleyer, G., and Schucking, G., Ber., 76B,678 (1943). Hooker Electrochemical Co., unpublished work. Ipatieff, V. N.,"Catalytic Reactions at High Pressures and Temperatures," New York, MacMillan Co., 1938. Kaufman, W. E., and Adanis, R., J . Am. Chem. SOC.,45, 3029
That furfural and its derivatives are versatile compounds capable of yielding numerous products by simple treatment with hydrogen is apparent from the reports cited. -4s more work is done in this field, it is entirely within the realm of reason to expect that other int,eresting and useful chemicals will join the ranks of furfuryl and tetrahydrofurfuryl alcohol in the parade of commercial products made by the catalytic hydrogenation of furfural and its derivatives.
(1923).
Krase, K~ TV., et al., Chem. &. M e t . Eng., 37, 530 (1930). Leuck, G. J., Porkorny, J., and Peters, F. K., U. S. Patent 2,097,493 (Kov. 2 , 1937). Orlov, N. A,, Compt. rend. acad. sci. U.R.S.S., 4,238 (1934). and Radchenko, 0. H., J . Applied Chem. (U.S.S.R.),9, 249 (1936). Paul, R., Bull. SOC. chim. (6). 5, 1053 (1938). Paul, R., and Hilly, G., Compt. Rend., 208, 389 (1939). Robinson, J . C., and Snyder. H. R., Org. Sgntheses, 23, 70 (1943). Schniepp. L. E., Geller, H. H., and Von Korff, R. W., -7. Am.
LITERATURE CITED
(1)
(2) (3)
(4) (5) (8)
(7) (8)
(9) (10)
Adkins, H., "Reactions of Hydrogen with Organic Compounds over Copper Chromium Oxide and Kickel Catalysts," hIadison, Cniv. of Wis. Press, 1937. Adkins, H., and Winans, C. F., C. S.Patent 2,175,588 (Oct. 10, 1939). Burnette, L. W., Rubber Ciiem. Technol., 18,284 (1945). Calingaert, G., and Edgar, G., IND.ENG.CHEM.,26, 878 (1934). Ellis C., "Hydrogenation of Organic Substances," New York, D. Van Nostrand Co., 1930. Gilman, H., and Calloway, N. O., J . Am. Chem. Soc., 55, 4197 (1933). Gilnian, H., and Young, R. V., Ibid., 56, 464 (1934). Gordon, J. T., U. S.Patent 2,364,358(Dec. 5 , 1944). Groggins, P. H., "Unit Processes in Organic Synthesis," New York, McGram-Hill Book Co., 1936. Hilditch, T. P., "Catalytic Processes in Applied Chemistry," New York, D. T'an Nostrand Co.. 1937.
Vol. 40, No. 2
Chem. Soc., 69, 672 (1947).
Shuikin, N. I.. and Daiber, T'. V., Bull. Acad. Sci, U.R.S.S., Claw sci. chim., 1941,121. Tongue, H . , "The Design and Construction of High Pressure Chemical Plant," London, Chapman 8: Hall, Ltd., 1934. Topchiev, K. S., Compt. r e n d . acad. sci. V.R.S.S., 19, 497 (1938). Weygand, C., "Organic Preparation," Kew York, Interscience Publishers, In?., 194.5. Williains, 3.l',, Compt. rend. m a d . s c i . C.R.S.S., 1930-A,523. Winans, C. F.. U. S.Patent 2,217,630 (Oct. 8, 1940). RECEIVEDOctober 9, 1947.
CHEMICAL INTERMEDIATES FROM FURFURAL OLIVER W. CASS E. I.
DU PONT D E N E M O U R S & COMPANY.
INC..
N l A G A R A FALLS. N. Y.
The reactions of two chemical intermediates (tetrahydr ofuran and dihydropyran) prepared from furfural are summarized. Tetrahydrofuranis prepared by a two-step process involving the removal of carbon monoxide from furfural to form furan, followed by hydrogenation of this compound. Dihydropyran is prepared from furfural by hydrogenation of furfural to tetrahydrofurfuryl alcohol, followed by dehydration and ring expansion of this alcohol to dihydropyran. Tetrahydrofuran can be reduced to butanol, oxidized to butyrolactone or to succinic acid, dehydrated to butadiene, chlorinated to a reactive dichloride, and reacted with a wide variety of reagents to open
the ether linkage and yield 1,4- derivatives of n-butane, such as the chlorohydrin, the dichloride, and esters of 1,4butanediol or, under other conditions, polymers and copolymers of this diol. Dihydropyran, containing a highly reactive double bond, reacts by addition with compounds such as hydrogen, water, chlorine, hydrogen chloride, hypochlorites, phosgene, alcohols, glycols, and organic acids. It may be also polymerized to a series of polymers ranging from viscous sirups to hard, brittle resins. Pyrolysis of dihydropyran is a convenient laboratory method for the preparation of acrolein. Many of the compounds resulting are of interest as chemical intermediates.
T
other routes t o these same compounds exist, and the position of furfural as a chemical raw material is therefore competitive, For example, tetrahydrofuran, which can easily be made from furfural, vas actually manufactured on a large scale in Germany during the war, from formaldehyde, acetylene, and hydrogen, and has rerently been announced in the United States a3 a product from the oxidation of petroleum hydrocarbons. ddiponitrile can be made not only from furfural but also from chemicals derived from coal or petroleum. The eventual choice of furfural as a ram material over chemicals from petroleum or coal in the years t o come may be based upon its yearly replenishment, but, at the present stage of our chemical development, the choice must be based on sound economic grounds. A number of lines of chemical attack on furfural have been developed in the research laboratories of the D u Pont Company. Two of these are of major importance in the synthesis of straightchain alpha, omega-disubstituted organic compounds containing 4, 5, 6, or 7 carbon atoms. These two lines of attack on furfural are ( a ) catalytic ienioval of the aldehyde side chain to give furan,
HE use of furfural as a raw material for the manufacture of adiponitrile, a nylon intermediate, was announced the spring of 1947 at the National Farm Chemurgic Conference. At the same time it was also disclosed that an extensive research program on the utilization of furfural as a source of other chemicals Df potential usefulness had been under way for several years. Not only in the United States, but also in Great Britain and Germany, the exploration of this field of chemistry has occupied the attention of strong research teams during the war years. Currently this is indicated by the offering in the British journals of commercial quantities of some ten new chcmicals derived from furfural, and the publication of reports of wartime applications for many furfural derivatives in Germany. Indications that chemists of the Soviet Cnion are also active in this field can be gathered from current chemical literature. It would appear, as is often the case, that industrial utilization of a raw material arrives simultaneously throughout the world. hlthough furfural is a convenient starting point for the synthesis of a vide variety of aliphatic and heterocyclic chemicals,
INDUSTRIAL A N D ENGINEERING CHEMISTRY
February 1948 HC-CH
11
(I) H C
*
11 H C-CsO
\O/
II CH
+co
FUQAN
%
TETRAk!YDROFURAN THF"
FURAN
FURFURAL
TETRAHYDROFURFURYL ALCOHOL
'
I1
HC
' 0 '
FURFURAL
Figure 1.
H C - CH
T E T R A H Y DROFURFURY L ALCOHOL
DIHY~QOPYFAN
DHP
Processes for tetrahydrofuran and di hyd ropyran
followed by hydrogenation of this compound to tetrahydrofuran, and (a) hydrogenation of furfural t o tetrahydrofurfuryl alcohol followed by catalytic dehydration of this compound to dihydropyran (Figure 1). All of these reactions may be carried out commercially as continuous processes and, with adequate control of reaction conditions, are capable of being operated in each case to give high yields of the desired products. Conversion of furfural to furan is readily carried out by passing a mixture of furfural vapor and steam a t 400" C . over a catalyst consisting of a mixed chromite of zinc and either manganese or iron. Hydrogenation of furan t o tetrahydrofuran occurs in th,e presence of catalysts such as nickel, Hydrogenation of furfural to tetrahydrofurfuryl alcohol may be performed either as a two-stage or as a one-stage catalytic hydrogenation. The tetrahydrofurfuryl alcohol resulting from this hydrogenation is dehydrated to form dihydropyran by passing the vaporized alcohol over a dehydration catalyst, such as alumina gel, a t elevated temperatures. Tetrahydrofuran and dihydropyran may thus be considered two major new chemical intermediates derived from furfural.
hydration of tetrahydrofuran to butadiene was operated on a large scale in Germany during the war as a part of the synthetic rubber program. It is estimated that one fifth of all the butadiene produced in Germany during the war was made by this process. I t consisted simply of passing tetrahydrofuran vapor mixed with steam over a phosphate catalyst a t 270" C. Neither the butanol nor the butadiene process is of value in present Americy economy, but the butadiene process is of interest as an example of the determined ingenuity which desperation gives to chemists. Oxidation of tetrahydrofuran using air or oxygen in the presence of a cobalt catalyst yields butyrolactone. This oxidation is best carried out a t 120" C. and some 100-200 pounds pressure. Butyrolactone was produced commercially in Germany during the war primarily as an intermediate for the manufacture of synthetic blood plasma used under the name Periston. Periston was polyvinyl pyrrolidone and was manufactured by reacting ammonia with butyrolactone to form pyrrolidone, followed by reaction of this compound with acetylene to yield monomeric vinyl pyrrolidone, which was then polymerized to form the plasma substitute. Chlorination of tetrahydrofuran proceeds readily a t moderate temperatures under the influence of light or other activating agents to yield primarily 2,3-dichlorotetrahydrofuran. This material is unusual in that the No. 2 chlorine atom, being alpha to an ether group, is highly reactive, reacting with compounds containing active hydrogen such as alcohols, glycols, and water, t o give the ether, diether, or hydroxy derivatives. The No. 3 chlorine atom, on the other hand, is extremely stable and unreactive. The ring opening reactions of tetrahydrofuran are legion. The most important of these reactions is the use of hydrogen
'
HzC-CHz
I
CH~CHtCHzCHzOH
HzC CHI
\ /
n-BUTANOL
0
.
HeC-CHz OXIDIZED
*
l
Sisler, H. $., Ohio State University, private communioation (1947).
I
t
HzC
\ I
C=O
0
BUTYROLACTONE
0x1 DlZLD
5
HOOCCH&HeCOOH SUCCINIC A C I D
CHLORINATED
HpC-CHCl
R o H iH z C
HzC I CHCl I
- CHCl
I
1
\ / 0
TETRAHYDROFURAN
Tetrahydrofuran is a colorless, mobile liquid with a characteristic etherlike odor. The boiling point a t 760 mm. pressure is 66' C., the freezing point is extremely low' (- 107" to -108' C . ) . The compound is lighter than water, with a specific gravity d:' of 0.888. Tetrahydrofuran is miscible in all proportions with water and with most of the common organic solvents. Tetrahydrofuran is a reactive compound (Figure 2). It can be reduced t o n-butanol, oxidized to butyrolactone or t o succinic acid, dehydrated to butadiene, and chlorinated to a reactive dichloride. It can be reacted with other reagents to open the ether linkage and yield 1,4- derivatives of n-butane, such as the chlorohydrin, the dichloride, and esters of 1,4-butanediol or, under other conditions, an almost infinite number of polymers and copolymers of this diol. Further hydrogenation of tetrahydrofuran with a nickel-type catalyst under vigorous conditions yields n-butanol. The de-
217
2,3-DICHLOWTETRAHYDROFURAN
HYDROCHLORINATED
CICH2CHZC~ec~ cbz I,4-DICHLOROBUTANC
ACETIC ANHYDRIDE
CH~COOCH~CHZCH CHtOOCCHy Z I,4-BUTANEDIOL DIACETATE
POLY M E R l Z E O
POLY T E T R A H Y D R O F U R A N
Figure 2.
Reactions of tetrahydrofuran
218
Vol. 40, No. 2
INDUSTRIAL AND ENGINEERING CHEMISTRY
CI CHzCHzCHzCH,CI
2NaCN
cNCCHzCHpCH2CH2CN ADIPONITQILE
INaCN C .;I
CHZCH~CH~CH~CN
DELTA- CHLOQOVALERON ITRILE
TETRAHY DQOPY PAN HYDROGENATEDt
HOCH~CHZCHZCH~CHZOH I,5-PENTANEDIOL
P HYDRATED
\ C H ~s HO(CH,),CHO I
ti2;'
~
B l S - [ 4 - C Y A N O 0UTYL)SULPHlDE
HZC\O/CHoH 2-HYDROXY-
4- HYDROXY-
TETRAHYDROPYRAN VALEPALDEHYDE HzC
CHp
\ /
TETRAHYDRDTHIOPHENE
Figure 3.
Reactons of 1,4-dichlorobutane
chloride to open the ring under vigorous reaction conditions giving 1,4-dichlorobutane as the only product. One of the simplest methods of carrying out this reaction is to pass a mixture of tetrahydrofuran and aqueous hydrogcn chloride under 15-20 at inospheres pressure through a reactor maintained at 180" C. 11desired, dehydrating agents such as sulfuric acid may be added t o this system. With a proper choice of reaction concentration and recycling of by-products, substantially quantitative yields of 1,4-dichlorobutane are secured. 1,4-Dichlorobutane is of major interest as an intermediate in the manufacture of adiponitrile by reaction with sodium cyanide in an appropriate solvent (Figure 3). By proper choice of reaction conditions, however, 6-chlorovaleronitrile may be made the major product of this reaction. 6-Chlorovaleronitrile serves as an interesting starting point for a series of longer chain bifunctional derivatives, as it readily reacts with sodium sulfide t o form bis-(4-cyanobutyl) sulfide. This compound is in the range of carbon content and boiling point of scbaconitrile. Both this sulfide and the corresponding sulfone may be converted into the acid, the diamine, and a variety of esters M hich reseQible the sebacates in many properties. Tetrahydrothiophene may be prepared in good yield by the reaction of 1,4-dichlorobutane with sodium sulfide. This reaction offers a convenient laboratory method for the preparation of this compound. Highest yields are secured when the sodium sulfide is prepared in an anhydrous alcohol system from hydrogen sulfide and sodium alcoholate. Tetrahydrofuran may be treated xyith acetic anhydride under proper conditions to give a sniooth opening of the cyclic structure t o the diacetate of 1,4-butane diol From this compound the diol itself may be prepared by hydrolysis; while other esters of the diol may be produced by acid interchange. This route to I,.l-butanediol and its derivatives is competitive with the butanediol process based on acetylene and formaldehyde. -4great deal of research work Tvas carried out in Germany during the war on the preparation of polymers and copolymers of tetrahydrofuran for use as synthetic lubiicating oils. This polymerization of tetrahydrofuran involves the opening of the ring by mea9s of the proper catalyst system and the formation of a long-chain polyether, with the catalyst appearing as an end group on the chain. For example, when the usual catalyst system consisting of thionyl chloride and ferric chloride is employed, the polyether contains chlorine, which is customarily removed by reflux with sodium methoside, replacing the chlorine atom with a methoxy group. The usual copolymers of tetrahydrofuran prepared in Germany were those with either ethylene oxide or propylene oxide. Copolymerization of the latter compound yields oils with lower pour points. The reaction with propylene oxide is extremely vigorous, so t h t proper control must be used to prevent accident.
OXIDIZED
DITETQAHYDROPYRYL ETHER
.
HOOCCH~CHzCH~COOH GLUTARIC ACID
C
/ \
OXIDIZED
HzC,
,C-0 0
VALCROLACTONE
p CHLORINATED
HzS/
\cHcl I
P ~
/CUCl
HzC,
0
2,3-DI CH LOR0 TETRAHYDROPYRAN
I
He?'
'CHCl
HLC CWOR \0 / 2-ALKYL ETHERS O F 3-CHLOROTETRAHYDROPYQAN
CuCN
e2 H'$
/=\
HpC\
:HCI FHCN
0 Z-CYANO.3-CHLOROTETRAHYDROPYQA N
HYDROCHLORINATION
"ce C / \ Hz$ 7'2
Z-CHLORCTETRAHYDRCPYRAN
Z.CHLORO-3-7ETRAHYDRCPYROIC ACID CHLORIDE
PYROLYSIS
Figure 4.
2,3-DIHYDRO5-PYQOIC ACID CHLOPIDE
CH~'CH~+CHZ= CHCHO ACQOLEI N
Reactions of dihydropyran
The introduction of dibasic acids or other glycols to this active polymerization systein also results in modification of the polymer produced. I n addition t o the chemical properties of tetrahydrofuran already discussed, mention should be made of the extraordinary solvent properties of this compound. It is an excellent solvent for synthetic resins such as the cellulose esters and ethers, synthetic rubbers, and alkyd resins. It is also one of the best sol-
February 1948
_L
INDUSTRIAL A N D ENGINEERING CHEMISTRY
vents for chlororesins of the vinyl chloride or vinylidene chloride type. Its moderate boiling point makes the use of tetrahydrofuran attractive as a film-casting solvent for these resins. For use in film castjng it may be utilized alone or to "pep up" cheaper or less active solvents. Tetrahydrofuran is also a n excellent medium in which t o carry out the Grignard reaction. The boiling point of tetrahydrofuran allows a reaction temperature some 30' higher than is the case when diethyl ether is used as the solvent. Tetrahydrofuran slowly forms an explosive peroxide when exposed to air, as do other ethers. Commercial tetrahydrofuran contains an antioxidant as a stabilizer against peroxide formation, However, all samples of tetrahydrofuran should be examined for peroxides by the usual acid potassium iodide tebt before use or distillation. If peroxides are present, tetrahydrofuran should be treated by any of the usual methods for peroxide removal before use or distillation. These methods include reflux with sodium or caustic, hydrogenation, or treating with a ferrous sulfate-sodium hydrogen sulfate solution.
P
/ \
HzC
CH
"IC,
FH
I
I1
219
-
H O C H ~ C H ~ C H ~ C H 2 C H ~ O H - CI ( C H E ) ~ C I
0
DlHY DROPYRAN
I,I-PENTANE DIOL
I,5-DICHLOROPENTANE
DIHYDROPY RAN
The second of the two major chemical intermediates derived from furfural is dihydropyran. This compound is a colorless mobile liquid with a characteristic penetrating etherlike odor. The boiling point of the compound is 86' C. a t 760 111111. This material is somewhat lighter than water with a specific gravity d:' of 0.923. It is soluble in water a t 20' C. t o the extent of 3 grams in 100 cc. It is soluble in most common organic solvents. Dihydropyran also possesses great chemical reactivity (Figure 4). The double bond is reactive, adding such widely varied materials as hydrogen, water, chlorine, hydrogen chloride, alkyl hypochlorites, phosgene, alcohols, glycols, and organic? acids, In most cases these additions take place readily and form the expected additive in high yield. In many cases these additive compounds themselves are reactive and useful as chemical intermediates. Dihydropyran may also be polymerized t o a series of polymers ranging in properties from viscous sirups t o hard, brittle resins. Pyrolysis of dihydropyran is a convenient laboratory method for the preparation of small amounts of acrolein. Hydrogenation of dihydropyran may be carried out with the usual hydrogenation catalysts, such as nickel, t o yield either the corresponding saturated cyclic ether, tetrahydropyran, or the open chain hydrated product, 1,5-pentanediol. The essential difference in these two hydrogenations lies in the addition of water t o the hydrogenation system in the latter case. Dihydropyran reacts with water containing a trace of acid to yield the additive product, 2-hydroxytetrahydropyran. I n case only a small excess of water is present in the reaction mixture, 2-hydroxytetrahydropyran will also add to dihydropyran forming the corresponding ether. Either of these two compounds can be hydrogenated t o 1,5-pentanediol in the presence of water. Tetrahydropyran is also a good solvent for synthetic and natural resins. It is generally not so active as tetrahydrofuran; nevertheless its higher boiling floint in some cases makes its use more attractive than tetrahydrofuran as a solvent. Tetrahydropyran also forms peroxides on exposure t o air. Although commercial tetrahydropyran is stabilized against peroxide formation, the same precautions in handling this compound should be taken as are taken with tetrahydrofuran. 2-Hydroxytetrahydropyran is the cyclic acetal of 4-hydroxyvaleraldehyde and, in aqueous solution, exists in equilibrium with this compound. Hydrogenation of this mixture in the presence of a large excess of ammonia yields the interesting amino alcohol, 5-aminopentanol-1. By use of the appropriate amine in place of ammonia, many compounds of interest as side chains on 8-aminoquinoline for use as antimalarial drugs may be produced. The same principles that apply to the oxidation of tetrahydrofuran apply also to the oxidation of dihydropyran. Oxida-
tion by nitric acid can be carried out to give good yields of high purity glutaric acid. On the other hand, air oxidation of dihydropyran in contact with cobalt catalysts and water leads t o the formation of valerolactone. Valerolactone can also be formed by the passage of 1,5-pentanediol over copper at an elevated temperature. A variety of chlorine compounds may be prepared by the addition of the appropriate reagent to the double bond of dihydropyran. The addition of chlorine yields 2,3-dichlorotetrahydropyran, in which, as in 2,3-dichlorotetrahydofuran, the No. 2 chlorine atom is reactive, combining with water, alcohols; *and glycols t o liberate hydrogen chloride and form the corresponding chloroacetals. I n these acetals the remaining chlorine atom is unreactive. By treatment with basic reagents, 2,3dichlorotetrahydropyran gives 3-chlorodihydropyran, a stable vinyl chloride-type halogen compound, whereas reaction with cuprous cyanide yields 2-cyano-3-chlorotetrahydropyran. Hydrogen chloride adds t o the dihydropyran to form 2-chlorotetrahydropyran. Phosgene reacts with dihydropyran by addition to yield an unstable derivative, which upon heating gives a fair yield of 2,3-dihydro-5-pyrolylchloride; this in turn can serve as the starting point for a variety of interesting new compounds. The preparation of 1,5-dichloropentane from dihydropyran follows a somewhat different course bhan that of 1,4-dichlorobutane from tetrahydrofuran (Figure 5). The opening of the six-atom ring of tetrahydropyran with hydrogen chloride is much more difficult than that of the five atom ring of tetrahydrofuran, so that it is preferable t o proceed by way of 1,6pentanediol. The sequence of reaction is then; dihydropyran, 1,5-pentanediol, 1,5-dichloropentane, rather than dihydropyran, tetrahydropyran, 1,5-dichloropentane. Reaction of hydrogen chloride with the diol is easily carried out; the only by-product is a small amount of tetrahydropyran, because of the tendency of the half-hydrochlorinated diol to cyclize. From 1,5-dichloropentane by reaction with sodium cyanide either pimelonitrile or 5-chlorocapronitrile is produced. Hydrolysis of pimelonitrile t o pimelic acid and reduction to heptamethylene diamine by the usual procedures offer simple routes to both of these compounds. 5-Chlorocapronitrile, by reaction with sodium sulfide, again leads t o a series of difunctional sulfides and sulfones. Although this discussion is an outline of only a portion of the field of chemical intermediates derived from furfural, it should serve to indicate the potentialities in this field of chemistry. RECEIVED October 8, 1947.
