N
I
1 330
INDUSTRIAL AND ENGINEERING CHEMISTRY
O II
REI0 H. LEONARD Newport Industries, Inc., Pensacola, Fla.
Levwlinic Acid as a Basic Chemical Raw Material Large supplies are obtainable from low grade cellulose but .
b A literature survey reveals few actual uses b Experiments indicate high reactivity, allowing
..
formation of many
compounds
b This
report suggests applications
L E V U L I N I C acid is a major product of the controlled degradation of hexose sugars by acids. Because the supply of hexoses from cellulose-containing plant material is immense and replenishable, conversion of such materials into a single chemical product meets one of the requirements for a basic chemical raw material. T h e reactive nature of levulinic acid shown by the keto and carboxyl groups (Figure l ) , meets the second requirement.
Although levulinic acid has been known since the 1870’s, when many of its reactions were first established, it has never reached commercial use in any significant volume. Reasons for its slow development probably are expensive raw materials and low yield, excessive equipment cost for its production, and physical properties detrimental to easy recovery and handling. Hexoses are convertible to levulinic acid by essentially a process of dehydra-
tion and cleavage of a mole of formic acid. T h e theoretical yield from a hexose is 64.5%, but the literature as reviewed by Wiggins (76A) shows that only about two thirds the theoretical yield can be attained; the balance proceeds to insoluble residues. substantially the same yields from cellulose i n Douglas fir sawdust were a p p l y demonstrated by Frost and K u r t h in 1951 (54. Formation of levulinic acid from low-cost cellulosic products overcomes one of the major difficulties encountered in other processes.
General Properties Recent reviews on levulinic acid include one by Wiggins ( 7 6 A ) which covers the formation from carbohydrates, one by Morton (77A) which describes heterocyclic derivatives, and an industrial bibliography ( 7 4 4 . The literature since 1929 is reviewed here and pertinent references are summarized in a n Annotated Bibliography, pp. 1331-41 ; prior work is included in Beilstein’s “Handbuch der Organischen Chemie” ( 7 2 4 . T h e structure of levulinic acid and its relation to the angelica lactones are shown in Figure 1. Evidence for the two structures of levulinic acid is based upon ultraviolet absorption ( 6 4 , stable esters (37C), and the acetylated enols ( 8 A ) . Additional properties include the vapor pressure curve (754, binary azeotropes (7A, 9 A ) , absorption spectra (ZA, 6 A , 73A), dissociation constant (7A), enolization (704, and infrared ( 3 4 and x-ray data (44).
References (1A) Accascina, F., Ricerca sei. 24, 314-18 (1954); C.A. 48, 12519. (2A) Bandow, F., Biochem. 2. 294,124-37 (1937); C.A. 32, 1181. (3A) Bender, M. L., Figueras, J., J . Am. 75, 6304-5 (1953). Chem. SOC. (4A) Clark. G. L., Kao, H., Sattler, L., Zerban, F. W., IND.ENC.CHEW 41, 530-3 (1949). (5A) Frost, T. R., Kurth, E. F., Ta,@i 34, 80-6 (1951); C.A. 45, 4441. (6A) Gex, M., Arch. Phys. Biol. 10, 250-6 (1933); C.A. 27, 5248. (7A) Horsley, L. H., Anal. Chem. 21, 847 (1949). (8A) Hurd, C. D., Edwards, 0. E., Roach, J. R., J . Am. Chem. SOC. 66,2031-4 (1944). (9A) Lecat, M., Comfit. rend. 222, 733-4 (1946); C.A. 40, 4578. (10A) MeInikov, N. N., Rokitskaya;M. S., J . Gen. Chem. (U.S.S.R.) 15, 657-60 (1945); C.A. 40, 5702. (11A) Morton, A. A., Sugar Research Foundation, Sci. Rept. Ser. 8, (1947); C.A. 41, 6875. (12A) Prager, B., Jacobson, P., eds., Beilstein’s “Handbuch der Or-
(13A) (14A) (15A) (16A)
ganischen Chemie,” 4th ed., vol. 3, p. 671, Springer, Berlin, 1921 ; 1st suppl., p. 235 (1929); 2nd suppl., p. 430 (1942); vol. 17, pp. 252-3 (1933); 1st SUPPI., p. 139 (1934). Singh, B., Dean, G. R., Cantor, S. M., J . Am. Chem. Soc. 70, 517-22 (1948). Staley Mfg. Co., A. E., Decatur, Ill., “Levulinic Acid,” 1942; C.A. 36. 1612. Stull, D. ’R.,IND. ENG.CHEM.39, 522 (1947). Wiggins, I,. F., Advunces in Carbohydrate Chem. 4, 306-14, (1950).
b Salts of Levulinic Acid Calcium levulinate is the only salt of levulinic acid that has attained importance. I t is used for the intravenous injection of calcium and is advantageous in that a high concentration of calcium can be obtained in a small volume. Other levulinate salts are generally soluble in water but not in oils. VOL. 48, NO. 8
AUGUST 1956
1331
f
Literature on Salts of Levulinic Acid Product and/or Use Preparation of Ca, Mg, Cd, Ni, and M n salts Solubility of calcium levulinate in water Conductivity of calcium levulinate solns. Manufacture of salts from esters Medical studies and applications on use of calcium levulinate, metabolism, etc. Use of Ca, Na, and NHI salts for promoting plant growth Phenyl mercuric levulinate as germicidal detergent and cosmetic composition Forms and behavior of Ag salts Na salt as antifreeze Controlled polymerization of furfuryl alcohol with sodium levulinate Bismuth levulinate Grease composition with lithium levulinate Grease composition with sodium levulinate Plasticizing cellulose materials with ethanolamine salt Low toxicity antimony composition with sodium gallate-levulinate Dispersing, wetting, and thickening agent with hydroxycyclo alkyl ammonium levulinate Levulinate salts of atropine, ephedrine, adrenaline, and proccaine Levulinic acid as solvent in procaine anesthetic solution Theobromine-levulinates for diuretic Topical anesthetic with p-aminobenzoate and levulinic acid Salts with 3-dihydropyridazones Soluble salt of bis-(0-methoxypheny1)isopropyl-N-methyl amide with levulinic acid S-1-Naphthylmethyl thiuronium chloride for preparation of characterization salt
\
References
(1B) Benson. W. L.. U. S. Patent 2.395., , 446 (Feb. 26, 1946). (2B) Bonner, W. A,, J . Am. Chem. SOC.70, 3308-9 (1948). (3B) Cox, G. J., Dodds, M. L. (to Niacet Chemical Corp.), U. S. Patent 2,033,909 (March 17, 1936). (4B) Cox, G. J., Dodds, M. L., Clasper, C., J . Am. Pharm. Assoc. 23, 662-4 (1934); C.A. 28, 6047. (5B) Curtis, D., U. S. Patent 2,382,546 (Aug. 14,1945). .
I
Esters of Levulinic Acid Ethyl levulinate is used for flavoring. Trade reports indicate that a few esters from high boiling alcohols have found use as plasticizers. T h e esters are relatively easy to make with monohydric and some polyhydric alcohols. References
(1C) Adelson, D. E., Dannenberg, H. (to Shell Development Co.), U. S. Patent 2,475,273 (July 5, 1949). (2C) Bader, A. R., Vogel, H. A., J . Am. Chem. Sac. 74, 3992-4 (1952). (3C) Billman, J. H., Rendall, J. L., Ibid., 66, 745-6 (1944). (4C) Britton, E. C., Coleman, G. H. (to Dow Chemical Co.), U. S. Patent 2,321,897 (June 15, 1943). (5C) Bruson, H. A. (to Resinous Products and Chemical Co.), Zbid., 2,395,452 (Feb. 26,1946). (6C) Bruson, H. A , , Riener, T. W., J. Am. Chem. SOC.67, 1178-80 (1945). (7C) Clifford, A. M. (to Wingfoot Corp.), U. S. Patent 2,448,703 (Sept. 7, 1948). (8C) Coleman, G. H., Hadler, B. C., Sapp, R. W. (to Dow Chemical Co.), Zbid., 2,359,622 (Oct. 3 , 1944). (9C) Cowley, M. A., Schuette, H. A., J . Am. Chem. Sue. 55, 387-91 (1933). (1OC) Cox, G. J., Dodds, M. F., IND.ENG. CHEM.25, 967-8 (1933). (11C) Cox, G. J., Dodds, M. F., J . Am. Chem. SOC.55, 3391-4 (1933). (12C) Cox, G. J., Dodds, M. F. (to Niacet Chemical Corp.), U. S. Patent 2,029,412 (Feb. 4, 1936).
1 332
\
Ref. (22B ) (4B) ( 75B) (3B) (72B) (7B) (77B)
(7 0 ~ ) ( 76A ) (13B) (8B)
(7B) ( 79B) (2OB1 (78B) (9B) (74B) (77B) (5B) (76B) (6B) (27B) ( 73B) (2B)
J
(6B) Ibid., 2,518,525 (Aug. 15, 1950). (7B) Easson, A. P. T., Pyman, F. L., J . Soc. Chem. Znd. 52. 97-9 (1933): C.A. 27, 3200. (8B) Foxon, G. H., Imperial Chemical Industries, Brit. Patent 677,848 (Aug. 20, 1952); C.A. 47, 346. (9B) Friedheim, E. A. H., U. S. Patent 2,466,019 (April 5, 1949); Brit. Patent 633,370; C.A. 45, P1736. (10B) Furcht, M., Lieben, A., Bull. soc. chim., (4) 5 , 1069-71 (1909); C.A. 4, 581. (11B) Goyan, F. M., Daniels, T. C., J. Am.
f
(12B)
(14B) (l5B) (l6B)
Pharm. Assoc. 30, 98-105 (1941); C.A. 35, 4549. Greville, G. D., Dodds, E. C., Brit. iMed. J . 1931, 11, 190; C.A. 25, 5952; see also C.A. 27, 4304; 30, 7696; 32, 652; 33, 5499; 34, 1125; 35, 175; 36, 828; 38, 979. 1030: 39. 1962. 3877: 41. 220; 2479; 42; 7872; 89521 43; 310, 5502; 44, P7869; 45, 828, 10402; 46,923i; 48,4706,13161. Heinzelmann, R. V., J . Am. Chem. SOC.75, 921-5 (1953). Holt, H. S. (to E. I. du Pont de Nemours & Co.), U. S. Patent 2,079,613 (May 11%1937). Jensen, A. S., Unangst, M. R., J . Chem. Phys. 9, 195 (1941). Kern. C. J., Del Vecchio. H . W. (to .4merican Home Products Corp.), U. S. Patent 2,562,865 (July 31, 1951): Brit. Patent 695.594 ( A u a . 12, 1953); C.A. 48, P958. Lever Bros., Ltd., Brit. Patent 427,324 (April 23, 1335); C.A. 29, 6366. Meigs, F. M. (to E. I. du Pont de Nemours & Co.), LJ. S. Patent 2,191,897 (Feb. 27, 1940). Moore, R. J., Saarni, W. (to Shell Development Corp.), Zbid., 2,614,077 (Oct. 14, 1952). Morway. A. J., Smith, P. V. (to Standard Oil Development Go.), Ibid., 2,690,429 (Sept. 28, 1954). Overend, W. G., Wiggins, L. F., J . Chem. Sac. 1950, 3508-11; C.A. 45,6641. Proskouriakov, A , , J . Am. Chem. Sac. 55,2132-4 (1933). ~y
(17B) (18B) (19B) (20B) (21B) (22B)
Literature on Esters of Levulinic Acid Boiling Point, a C. Profiosed Uses 197.7 Sitrocellulose solvents 206.2 221.2 208.2 237.8 229.9 253.2 247.9 266.8 133-6 (40 mm.) 199-202 (40 mm.) 208-10 (40 mm.) 283.5 291.1 298.0 Nonyl Decyl 306.5 225.8 see-Butyl 239.6 Methyl isopropyl Diethyl carbinyl 239 247.2 2-Methyl butyl 246 Pentasol 181-3 (17 mm.) Benzyl Poor antispasmodic 148-50 (3 mm.) Methyl and ethyl Component in hydraulic fluids 175-90 (5 mm.) Lauryl Pl.%sticizersfor cellulose plastics 180-200 (1.5 mm.) Stearyl Benzyl and 6 to 18 carbon alcohols Ethoxyethyl 108 (5 mm.) Plasticizers for cellulose plastics Butoxyethyl 150-75 (11 mm.) Coconut oil diglyceride Coconut oil monoglyceride Hydrogenated castor oil Lauroxyethyl 170-90 ( 1 . 5 mm.) Phenoxyethyl 165-6 (2 mm.) Ethoxyethoxyl ethyl 139-40 (2 mm.) In solvent refining oil Methyl, ethyl, propyl, butyl, and amyl Ester Methyl Ethyl Propyl Isopropyl Butyl Isobutyl Amyl Isoamyl Hexyl
INDUSTRIAL AND ENGINEERING CHEMISTRY
or
Alcohol
7 Ref. ( 70C)
(720
(3C) (36C) ( 78C) (330
(34C)
(28C)
Aryloxy alkyl Dihydronordicyclopentadienol
190 (10 mm.)
2-Butene-I,4-diol
158-60 (1 mm.) 210-16 (8 mm.)
Plasticizers for polystyrene Plasticizer for rubber, hydraulic fluids, ink Wetting agent, detergent emulsifier Plasticizer
2,2-Di-( &hydroxyethoxyp heny1)-propane 2-Haloallyl Methyl and ethyl
Copolymer with butadiene For fractionation of tall oil In styrene-maleic resin composition For toxicity study
Methyl Cyclohexyl
116-18 ( 2 mm.)
Pseudo esters Methyl Isopropyl Allyl Methyl isobutyl carbinyl Cyclohexyl Ethyl Propyl Butyl see-Butyl Phenyl Hexyl Benzyl 2-Chloroallyl Allyl Chloromethyldihydrosafrole Tetrahydrofurfuryl Allyl
113-15 (15 mm.) 113-15 (15 mm.) 130-2 (3 mm.)
Diethylene glycol benzoate
185-90 (0.3 mm.)
3-0~0-1,7-heptanediol 3-0xo-1,8-octanediol 3-0~0-1,9-nonanediol Methyl Dimethyl benzyl and 1-naphthyl carbinyl 2 to 8 carbon glycols
201-9 ( 0 . 4 mm.)
89-90 (15 mm.) 103-5 15 mm.) 106-8 [ l o mm.) 107-8 (2 mm.) 112-13 (1 mm.)
160-95 (1.5 mm.)
Copolymer with butadiene Polyallyl levulinate Insecticide Ineffective insect repellant Copolymer with maleic anhydride Plasticizers for poly(viny1 chloride)
Attempted transesterification Monoester plasticizers Plasticizers for cellulose acetate Plasticizers for poly(vinp1 chloride) Antifungal properties
Benzyl, cyclohexyl, and tetrahydrofurfuryl 2,4,6-Trichlorophenyl 2,4,6-Tribromophenyl Diethylene glycol, di209-16 ( 4 mm.) 245-6 (0.3 mm.) 1,4,3,6-Dianhydro-~-sorbitol Benzyl Monochlorobenzyl Dichlorobenzyl XYlYl Monochloroxylyl Dichloroxylyl Xylylene, diMonochloroxylylene, diDimethylxylylene, diy h t h y l , di-
Solvents, paint remover, lacquers, dissolve cuprous oxide films
Polyvinyl plasticizers
132-4 (2 mm. ) 147-9 (2 mm. ) 163-6 (2 mm.) 164-6.5 (3.5 mm.) 178-81 (4.5 mm.) 163-4 (1 , 5 mm.) 220-50 (1 mm.) 244-67 ( 0 . 5 mm.) 248-62 (4 mm.) 200-9 (4 mm.)
Preparation from sodium levulinate for use as plasticizers
(28C) Izard, E. F., Salzberg, P. L. (to E. I. du Pont de Nemours & Co.), U. S. Patent 2,004,115 (June 11, 1935). (29C) Jones, J. L. (to Libbey-Owens-Ford Glass Co.), Zbid., 2,533,376 (Dec. 12, 1950). (30C) Kawai, Y . , Uno, O., Takagi, M., Yamashita, Y., Ishii, Y., J . Chem. SOC.Japan 57, 158-60 (1954); C.A. 49, 11595. (31C) Langlois, D. P., Wolff, H., J . Am. Chem. SOC.70, 2624-6 (1948). (32C) Langlois, D. P., Wolff, H . (to A. E. Staley Mfg. Co.), U. S . Patent 2,493,676 (Jan. 3, 1950). (33C) Lawson, W. E. (to E. I. du Pont de Nemours & Co.), Zbid., 2,015,077 (Sept. 24,1935). (34C) Lawson, W. E., Salzberg, P. L., Zbid., 2,008,720 (July 23,1935). (35C) Longley, K. D. (to Quaker Chemical Products Co.), Zbid., 2,409,137 (Oct. 8, 1946). (36C) Sah. P. P. T.. Lei. H . H., Fang, ' H. M . , ' J . .Am. 'Chem. S o d . 59, 4727-8 (1933). (37C) Sah, P. P. T., Ma, S. Y., Zbid., 52, 4880-3 (1930). (38C) Ibid., 54, 3271-3 (1932). (39C) Sakai, S., Saito, G., Kada, T., Muraoki, N., Sato, A., J . Sci. Research Inst. (Tokyo) 48, 38-48 (1954); C.A. 48, 13974. (40C) Schuette, H. A., Cowley, M. A., J.Am. Chem. Soc.53,3485-9(1931). (41C) Smith, C. N., Burnett, D., Jr., J . Econ. Entomol. 42, 439-44 (1949); C.A. 44, 6567. (42C) Wachs, H . (to U. S. Industrial Chemicals), U. S . Patent 2,521,812 (Sept. 12, 1950). (43C) Wingfoot Corp., Brit. Patent 569,407 (May 23, 1945); C.A. 41, 5343. (44C) Yahama, Y., Hayashi, I. (to Ajinomoto Co.), Japan Patent 4322 (Sept. 2,1953); C.A. 48,9748. (45C) Yamashita, Y., Ishii, Y., J . Chem. Soc. Japan, Znd. Chem. Sect. 56, 547-9 (1953); C.A. 48, 12454. (46C) Ibid., 605-6 (1953); C . A . 48, 11836.
Reduction of Levulinic Acid(13C) Deebel, G. F. (to Monsanto Chemical Go.), Zbid., 2,366,667 (Jan. 2, 1945). (14C) Deichmann, W. B., Mergard, E. G., J. Znd. Hyg. Toxicol. 30, 373-8 (1948); C.A. 43, 1867. (15C) Emerson, W. S., Langley, R. I. (to Monsanto Chemical Co.), U. S . Patent 2,581,008 (Jan. 1, 1952). (16C) Emerson, W. S., Langley, R. I., Darby, J. R., Cowell, E. E., IND. ENG.CHEM.42, 1431-3 (1950). (17C) Frank, R. L., Armstrong, R., Kwiatek, J., Price, H. A., J . Am. Chem. SOC.70, 1379-81 (1948). (18C) Fulton, R. R. (to Puritan Soap Co.), U. S. Patent 1,986,260 (Jan. 1, 1935). (19C) Gerhart, H. L. (to Pittsburgh Plate Glass Co.), Zbid., 2,407,413 (Sept. 10, 1946). (20C) Gloyer, S. W., Vogel, H . A . , Zbid., 2,640,823 (June 2, 1953).
(21C) Govers, F. X. (to Indiana Refining Co.), Zbid., 2,087,473 (July 20, 1937). (22C) Green, C. E. (to General Tire and Rubber Co.), Ibid., 2,654,723 (Oct. 6, 1953). (23C) Hachihama, Y., Hayashi, I., J . Chem. SOC.Japan, Znd. Chem. Sect. 54, 695-8 (1951); C.A. 48, 3261. (24C) Hachihama, Y., Hayashi, I., Technol. Repts. Osaka Univ. 3, 191-200 (1953); C.A. 48, 3717. (25C) Hayashi, I., Hamada, S., Hachihama, Y., J. Chem. Soc. Japan, Znd. Chem. Sect. 56, 623-5 (1953); C.A. 49, 8822. (26C) Ishii, Y., Yamashita, Y., J . Oil Chemists SOC. (Japan) 2, 199-206 (1953); C.A. 48, 4877. (27C) Ishii, Y., Yamashita, Y., Takenouchi, M., Takasawa, S., J . Chem. Sod. Japan, Znd. Chem. Sect. 57, 667-70 (1954); C.A. 49, 8631.
Reduction of levulinic acid first yields 4-hydroxyvaleric acid, which, as the free acid, lactonizes readily to y-valerolactone (lactone of 4-hydroxyvaleric acid). Salts and esters of 4-hydroxyvaleric acid can be obtained. However, the esters change to the lactone upon distillation (780). Catalytic hydrogenation a t temperatures above 200' C. yields substantial amounts of 1,4-pentanediol, and smaller amounts of amethyltetrahydrofuran, and 1-pentanol. Levulinic acid has been reduced to yvalerolactone by means of sodium in alcohol (750), sodium amalgam ( 2 0 ) ) sodium and lithium borohydride ( 3 0 , 720)) and aluminum amalgam (740). Ethyl levulinate diethylacetal has been reduced by lithium aluminum hydride to 4-keto-1-pentanol in 56% yield (770). VOL. 48,
NO. 8
AUGUST 1956
1333
f
Catalytic Hydrogenations of Levulinic Acid
Reduction System Lev.a, nickel and aluminum oxides, 230 Lev., platinum oxide, 3 atm., 24' Esters, platinum oxide, 3 atrn., 24'
Ref.
Products
20% valeric acid with decomposition
Ethyl ester, Ni, 120 atm., 100 Na salt, Raney Ni, 330 atm., ,7j Lev., Raney Ni, 60 atm., 200
7-Valerolactone Hydroxyvalerate esters y-Valerolactone Ethyl-y-hydroxyvaleratr,85yG y-Valerolactone, 84y0 y-Valerolactone, 94'3
Ethyl ester, copper chromate, 200 atm.,
1,4-Pentanediol, 747,
250'
1,4-Pentanediol, 44Yc;a-methyltetrahvdrofuran y-Valerolactone, copper-barium chro- 1,4-Penianediol, 78%; 1-pentanol, mite, 300 atm., 250" 8% y-Valerolactone. copper chromite, 200 1,4-Pentanediol, 83q% atm., 260" a Levulinic acid. Lev., copper chromite, 200 atm., 300'
(8D) Hayashi, I., Negoro, E., Hachihama, Y . , J . Chem. Soc. Japan, Znd. Chem. Sect. 57, 67-9 (1954); C.A. 49,11554. (9D) Ishii, Y., Takagawa, S., Yamashita, Y., Kamata, S., Yobe, S., J. Chem. SOC. Japan, Znd. Chem. Sect. 57, 156-8 (1954); C.A. 49,
11554.
(40, 7 0 )
(40)
(6D)
(10D) Kyrides, L. P., Craver, J. K . (to Monsanto Chemical Co.), U. S. Patent 2,368,366 (Jan. 30, 1945). (11D)Lease, E. J., McElvain, S . M., J . Am. Chem. SOC.55, 806 (1933). (1 2D) Nystrom, R. F., Chaikin, S. W., Brown, W. G., Zbid., 71, 3245-6
(1949). (13D) Razuvaev, G.,Ber. 61B, 637--40 (1928); C.A. 22, 2142. (14D)Sasaki, S.,Ri, S., Bul. Sci. Fakultat Terkult. Kyushu Imp. Uniniu. Fukuoka 11, 86-90 (1944); C.A. 43, 5367. (4D)Christian, R. V.,Brown, H. D., (15D)Schuette, H . A., Sah, P. P. T., J . Am. CJiem. SOC.48, 3163-5 Hixon, R. Zbid., 69, 1961-3 (1926). (1947). (16D) Schuette, H.A., Thomas, R. W., (5D) Cdvert, L. W., Connor, R., Adkins, Zbid., 52, 3010-12 (1930). H., Zbid., 54, 1651-63 (1932). (17D) Swoboda, 'W., Mona'tsh. 8 2 , 388-91 (6D) Folkers, K . , Adkins, H., Zbid., 54, (1951); C.A. 46, 4482. 1145-54 (1932). (7D) HachihamzI; Y . , Imoto, M., J . SOC. (18D) Thomas, R. W., Schuette, H. .4., Chem. Ind. Jaban 45; 21 '(1942): Cowley, M. A , , J . Am. Chem. C.'4. 44, 8859: SO^. 53, 3861-4 (1931).
References
( l D ) Allen. B. B.. Wvatt. B. W.. Henze. H . ' R . , J. Am. 'Chem. SOL. SI; 843-6 (1939). (2D) BeEkenhe)m,-A: M., Dankova, T. F., J . Gen. Chem. (U.S.S.R.) 9, 924-31 (1939); C.A. 34, 368. (3D) Chaikin, S . W., Brown, W. G., J . Am. Chem. Sac. 71, 122-5 (1949). %
-7
,
(40)
Reaction of Levulinic Acid with Carbonyl Reagents About 45 derivatives have been reported since 1929; 30 of these are hydrazones and semicarbazones prepared by Sah and others (23E). They are of interest for conversion into pyridazinones (Figure l ) , and for preparation of soluble derivatives of insoluble but biologically active materials. References
(1E)Allen. C. F. H., J. Am. Chem.
SOC.
52, 2955-9 (1930). (2E) Allen, C. F. H., Gates. J. W., J . Org. Chem. 6, 596-601 (1941). (3E) Amorosa, M., Ann. chim. farm. 1940, 54-69 (May); C.A. 34, 7910. (4E)Bennett, C. W., J . Am. Chem. Soc. 50, 1747-8 (1928). (5E) Bergman, M., Machemet, H., Be?. 66B, 1063-5 (1933); C.A. 27,
r
Reactions of Levulinic Acid with Carbonyl Reagents
Derivatives oj' Keto Group and C7~es Ketazine and ketazine of acid hydrazide 2,4-DinitrophenyIhydrazonesof acid and esters Phenylsrmicarbazone Phenylacetic hydrazone Semicarbazone and phenylhydrazone of acid and esters P-Thiocyanophenylhvdrazone Sulfapyridinylhydrazone of acid 1-Menthylhydrazone of ethyl ester, optically active 1-Methyl-3-carbopyridiniumhydrazones of acid and esters Hydantoin of acid Toxicity of levulinic semicarbazone to insects j-Carboxyphenylhydrazone of acid Absorption spectra of 2,4-dinitrophenylhydrazones Plant growth-promoting substances from ketone derivatives Xanthogenhydrazone of acid p-Nitrophenylhydrazone of esters 5-(p-~Methoxyphenyl)-1,2-dithiol-3-azine induces bile secretion Isonicotinylhydrazone of acid I
-J Ref.
(4E)
(7E, TOE, 77E, 7.9E, 25E) (7E, 23E) (24E) (5E, 6E, 78E, 2GE, 29B) ( 15E) (3E) (37E) (2E) ( 14E) ( 73E) (27E) ( 8 E , 12E, 16E) (20E) (28E) (ZTE, 22E) ( 7 7E) (9E, 2333, 30E)
A 7 7 Rv . I
I
I
Biquard, D.,Grammaticakis, P., Bull. sac. chim. 8, 246-54 (1941); C.A. 36, 2476. Bradfield, A. E., Francis, E. F., Penfold, A. R., Simonsen, J. L., J . Chem. SOC.1936, 1619-25; C.A. 31, 673. Braude, E. A , , J . Chem. Soc. 1945, 498-503; C.A. 40, 324. Carrara, G.: Chiaque, F. M., D'Amato,V., Ginoulhiac, E., Martinuzzi, c., Teotino, U. M., Visconti, N., Gazz. chim. ital. 82, 652-70 (1952); C.A. 48,
(14E)Henze, H.R.,Speer, R. J., J . Am. Chem. Soc. 64, 522-3 (1942). (15E) Horii, Z., J . Pharm. SOC.Jajan 56, 53-7 (1936): C.A. 30. 4156.
6423. Cowley, M. A , , Schuette, H. A., J. Am. Chem. SOG.55, 3463-6
(1933). Ekder,. ' A , , Arzneimittel-Forsch. 3, 557-9 (1933); C.A. 48, 4703. Errera, M., Greenstein, J. P., Arch. Bzochem. 15, 449-57 (1947); C.A. 42, 3443. Gertler, S. I.,U. S.Dept. Agr., Bur. Entomol. Plant Quarantine, E705, (1946); C.A. 41, 1794.
1334
INDUSTRIAL A N D ENGINEERING CHEMISTRY
Johnson, G. D., J . Am: Chem. Soc. 75, 2720-3 (1953). Kharasch. M.S.,Rudy, I., Nudenberg, W., Buchi, G., J . Org. Chem. 18, 1030--44(1953). LaForge, F. B., Barthen, W. F., Ibid.,
IO, 222-7 (1945). Matthiessen, G., Arch. Pharm. 284, 62-6 (1951); C . A . 46, 89. Moyer, W. W (to A. E. Staley Mfg. Co.). U. S. Patent 2.416.198 (Feb'. 18, 1947). Overend, W. G., Wiggins, L. F., J . Chem. SOC. 1950, 3508-11; C.A. 45, 6641. Percival, E. G. V., Somerville, J. C., J . Chem. SOC. 1937, 1615-19; C.A. 32, 121. Sah, P. P. T., others, J . Chinese Chem. SOC. 14, 39-44 (1946); I
_
C.A. 43, 6971, 6972, 6973; see also C.A. 27, 3164, 4222; 28, 3712, 3713; 29, 465, 466, 7298; 30. 2875 7104. 8074. 8148: 31; 655, 3825, 4266, 4267; 35;
4362: 48. 13789.
Seka, R.>Heilperin, St. P., Monatsh. 57, 45-51 (1931); C.A. 25, 1821. Strain, H. H., J . Am. Chem. SOC.57, Treibs,
--
\ - ' - - I .
W., Ann. 576, 116-24
(1952): C.A. 47. 3824. Ve'ibel, . S., Acta . Cfiem. Scand. 1, 54-68 (1947); C.A. 42, 1234. Wangel, J., Arkiv Kemi 1, 431-45 (1950); C.A. 44, 6818. M'eidenhagen, R., Korotkyi, B., Z. Wirtchaftsgrupje Zuckerind. 85, 131-6 (1935); C.A. 29, 7325. Wenner, W., J. O r , . Chem. 18, 1333-7 (1953). Woodward, R.B., Kohman, T. P., Harris, G. C., J . Am. Chem. Soc. 63, 120-4 (1941).
Reactions as a Ketone Alkyl metal halides react with levulinate esters to yield a serirs of y-substituted y-valerolactones (Figure 1), some of which are proposed for perfumes a n d flavors (SF, 77F, 33F). Aldehydes, particularly aromatic aldehydes, condense with levulinic acid i n CY, p, or 6 positions, depending upon the reaction conditions employed (75F, 26F). Products from these condensations have been converted into other derivatives, several of which may be of industrial significance (7F, 24F, 32F, 7K). Additional proposed uses include polymerization monomers, eelworm hatching agents, dibasic acids, plant hormones, emulsifiers, and vinyl chloride plasticizers.
f
References
y-HexylDihydroj asmone y-valerolactone ?-PhenylOptically active y-valerolactone y-Decyl-y-valerolactone
(1F) Baumgarten, H., J. Am. Chem. SOC. 75. 979 (1952). (2F) Beaver, D.'J., Throdahl, M. C. (to Monsanto Chemical Co.), U. S. Patent 2,535,664 (Dec. 26, 1950). (3F) Cason. J.. Adams. C. E., Bennett, L. L., 'Jr., Register, U. D., Jl Am. Chem. SOC. 66, 1764-7 (1944). (4F) Cason, J., Brewer, P. B., Pippen, E. L., J . Org. Chem. 13, 239-48 ,
I
(1 , 948) -._,. ~
Frank, R. L., Armstrong, R., Kwiatek, J., Price, H. A., J . Am. Chem. SOC. 70, 1379-81 (1948). Frank, R. L., ArYvon, P. G., Richter, J. W., Vanneman, C. R., Ibid., 66, 4-6 (1944). Hachihama, Y., Hayashi, I . , Makromol. Chem. 13, 201-9 (1954); C.A. 49, 11618. Hagemeyer, H. J. (to Eastman Kodak Co.), U. S.Patent 2,521,914 (Sept. 12,1950). Hayashi, I., Hachihama, Y., J . Chem. SOC. Japan, Ind. Chem. Sect. 57, 662-4 (1954); C.A. 49, 8604. Hayashi, I., Kumashiro, I., HachiJapan, hama, Y., J. Chem. SOC. Ind. Chem. Sect. 57, 299-300 (1954); C. A. 49, 13208. Heine and Co., A. G., Ger. Patent 639,454 (Jan. 21, 1937); C.A. 31, 3066. Holmberg, B., Arkiv Kemi, Mineral. Geob. f5A, No. 8, 1-15 (1942); C.A. 37, 85. Hull, D. C.. Arrett. A. H. (to Eastman Kodak"Co:), U. S: Patent 2,482,066 (Sept. 13, 1949). Hurd, C. D., Edwards, 0. E., Roach, J. R., J. Am. Chem. Sac. 66, 2013-14 (1944). Kato, H., Sci. Repts. Tokyo Bunrika Daigaku 2, 257-65 (1935); C.A. 30. 458. Long, J. R. (to Wingfoot Gorp.), U. S. Patent 2,391,252 (Dec. 18, 1945) ; 2,396,586. Morev, G. H. (to Commercial Solvents Corp.),'U. s. Patent 2,406,504 (Aug. 27, 1946). Moroe, T., Hattori, S.. Ikeeami. N.. J . Ph&. Sac. Jaflan 72; 1172-4 (1952); C.A. 47, 6337. Moroe. T.. Matsukura. J.. Pharm. Bull.. (Japan) 2, 92-5 ' (1954); C.A. 49. 13068. Picha, G.'M., J. Am. Chem. SOC. 75, 3155-9 (1953). Raha, C., J. Indian Chem. SOC. 30. 129-32.(1953); C.A. 48, 6960. '
Product 2-Allyl-3-methyl-3hydroxyadipic acid; 2-hexenyl-, 2-penten 1-, 2-(4-pentenyl-, 2-h-noneny1)?-Methyly-valerolactone
Reactions as Ketone Use Method Ref. Perfume intermediates Ethyltribromo acids, Zn, ( 7 I F ) 1 2 , and ethyl levulinate
y-Ethyl-y-valerolactone
Synthesis of isocitronel101, fatty acids, and cyclopentenones Fatty acid synthesis
y-Propyly-valerolactone y-Isopropyly-valerolactone ?-Butyl- y-valerolactone
Coconut flavors
y - Amyl-y-valerolactone
Alkyl-y-lactone Plasticizers 4,6,9-Triketocapric acid 4,7-Dimethyl-4hydroxycaprylic acid Lactone of monoethyl3-methyl-3-hydroxyadipate Acetylated enols of ethyl levulinate (ethyl-4-acetyl-3( and 4)-pentenoate Copolymers of acetylated enols
Methyl MgI and ethyl levulinate or cyclohexyl levulinate Ethyl MgBr and ethyl levulinate, or cyclohexyl levulinate Propyl MgBr and ethyl levdinate Isopropyl MgBr and cyclohexyl levulinate Butyl MgBr and ethyl levulinate Amyl MgBr and ethyl levulinate Hexyl MgCl and ethyl levulinate ( - )-Menthyl levulinate and phenyl MgBr Decyl MgBr and ethyl levulinate
Amyl MgBr and ethyl levulinate Synthesis of isocitronel- Isoamyl MgBr and ethyl levulinate lo1 Ethylmonobromoacetate ethyl levulinate, and Zn Polymerization Ketene, ethyl levulinate, (74F, 30F, 31F) and HzS04 Acetylated enols with sty- ( 8 F ) rene, methyl acrylate, and vinyl acetate Isopropenyl acetate and (8F, 73F) ethyl levulinate Aldehyde and levulinic ( 2 5 F ) acid with NaOAc, HCL or AczO Levulinyl chloride and (76F) benzaldehyde Furfural, levulinic acid, (24F) and alkali Aldehyde, levulinic acid, (2OF) and alkali
Acetylated enols of ethyl levulinate p- and 6-arylidene levu- Substituted naphthols linic acids from 14 and substituted ,, aldehydes benzo-octatrienes or-Benzallevulinic acid p-Furfurylidene levulinic acid 6-(@-Hydroxyphenyl)4-keto-5-hexenoic acid Furandipropionic acid
7
Tested for eelworm hatching agent Amino ester hydrochlorides Salts with hexamethylenediamine for nylon-type fiber Diketosebacic acid and bislactone of 4,7-dihydroxysebacic acid
5-Furfurylidene levulinic acid, 35-60 7 0 yield 5-Cyano-4-methyl-4pentenoic acid, 87'% yield 4-Carboxy-1 -methylPlant hormones 1,3-~yclopentadiene3-propionic acid, 6470 yield 4-(2-Hydroxymethyl-5hydroxy-4-pyrone-6)4-valer olact one Mercaptol with thioDerivative hydracrylic acid Bis-(octadecylmercapWaxes, detergents, to1)-valeric acid emulsifiers, dispersants, and wetting agents Butyl-2-methyl-5-ethyl- Poly(viny1 chloride) 5-nitro-2-m-dioxaneplasticization propionate, 72Y0 vield; ethyl ester Methyl 4-Cyano-4-Pen- Butadiene copolymer
Furfural, levulinic acid, and Na2C08 followed by HC1 hydrolysis Excess Na levulinate in furfural at 60". With NaOH or NaZCOg Ethyl cyanoacetate, ethyl levulinate, and piperidine Ethyl levulinate and sodium ethoxide
(7F, 9 F )
Kojic acid, ethyl levulinate, and NaHC08
(34F)
(IOF, 28F, 32F, 1K) (27F, 22F, 27F)
(28F)
( 72F)
Octadecylmercaptan and levulinic
(25F)
2-Ethyl-2-nitro-l,3propanediol and butyl levulinate
(17F)
Methyl levulinate, HCN, andacetic anhydride
(76F)
VOL. 48, NO. 8
AUGUST 1956
J 1335
(22F) Raha, C., J. Indian Chem. Soc. 30, 205-8 (1953); C.A. 47, 10329. (23F) Reid, J. A., Turner, E. E., J . Chem. Soc. 1951, 3219-23; C.A. 46, 9515. (24F) Russell, P. B., Todd, A. R., Waring, W. S., Biochem. J . 25, 530-2 (1949); . . C.A. 44, 8862. (25F) Schirm, E. (to Alien Property Custodian), U. S. Patent 2,369,612 (Feb. 13, 1945). (26F) Sen, R. N., Roy, B. C., J . Indian
(27F) (28F) (29F) (30F)
Chem. Soc. 7, 401-16 (1930); C.A. 24, 4763. Shemyakin, M. M., Trakhtenberg, D. M., J . Gen. Chem. U.S.S.R. 13, 552-6 (1943); C.A. 39, 497. Shimizu, S., Takei, S., J . Agr. Chem. Soc. Japan 23, 286-8 (1950); C.A. 44, 8868. Soloway, S. B., LaForge, F. B., J . Am. Chem. SOC. 69, 2244-5 (1947). Spence, 'J. A., Degering, E. F., Zbid., 66, 1624 (1944).
(31F) Spence, J. A. (to Purdue Research Foundation), U. S. Patent 2,407,301,2,407 302 (Sept. 10, 1946), Brit. Patent 605,471 (July 23, 1948); C.A. 43, 1436. (32F) Urban, R . S. (to Rohm Haas Co.), U. S. Patent, 2,688,621 (Sept. 7. 1954). (33F) Wiggins, 'L. F., Overend, W. G., MJg. Chemist 19, 369 (1948); C.A. 43, 784. (34F) Woods, L. L., J . Am. Chem. SOC. 75, 2008-9 (1953).
Oxidation, Halogenation, and General Applications Oxidation products include the peroxide, methyl vinyl ketone, a n d succinic, malonic, and acetoacrylic acids. I t is difficult to obtain specific halogenated products from levulinic acid itself. Items of general nature include the possible use in foods, a n d as a solvent i n liquid-liquid extraction of hydrocarbons. References
(1G) Bollens, W. F. (to Swift and Co.), U. S.Patent 2,476,802 (July 19, 1949). (2G) Bremmer, J. G. M., Jones, D. G. (to Imperial Chemical Industries), Brit. Patent 601,922 (May 14, 1948); C.A. 42, 7319. (3G) Dunlop, A. P., Smith, S. (to Quaker Oats Co.), U. S. Patent 2,676,186 (April 20, 1954). (4G) Fichter, Fr., Herndl, J., Helv. Chim. Acta 25, 229-40 (1942); C.A. 36, 5713. (5G) Fichter, Fr., Lurie, S., Helv. Chim. Acta 16, 885-91 (1933); C.A. 27, 4778. (6G) Furter, M. F., Haas, G. J., Rubin, S.H., J . B i d . Chem. 160, 293-300 (1945); C.A. 40, 2504. (7G) Gross, H. H., German, I. F. (to Texas Co.), U. S. Patent 2,383,057 (Aug. 21, 1945). (8G) Hara, Y., Fujise, S.,J . Chem. Soc. Japan, Pure Chem. Sect. 74, 698-9 (1953); C.A. 48, 11341. (9G) Helberger, J. H., Ann. 522, 269-77 (1936); C.A. 30, 5184. (10G) Hovey, A. G., Hodgins, T. S. (to Reichhold Chemicals), U. S. Patent 2,195,570 (April 2, 1940). (11G) Hughes, E. D., Watson, H . B., J : Chem. Soc. 1929, 1945-54; C.A. 24, 67. (12G) Hurd, C. D., Ferraro, J. R., J . Org. Chem. 16,1639-42(1951). (13G) Johnstone, C., Schumm, F. R. (to Dodge and Olcott, Inc.), U. S Patent 2,626,218 (Jan. 20, 1953): (14G) Jones, A . R., Dowling, E. J., Skraba, W. J., Anal. Chem. 25, 394-6 (1953). ( l 5 G ) Lewandowski, T., J . Dairy Sci. 35, 449-54 (1952); C.A. 46, 6578. (16G) Mashevitskaya, S.G., Plevako, E. A . , J . Appl. Chem. (U.S.S.R.) 11, 511-14 (1938); C.A. 32, 6288. (17G) Nakazaki, M., J . Japan Chem. 3, 108-10 (1949); C.A. 46, 4484. (18G) Nerheim, A. G., Estee, C. R., Univ. S. Dakota Bull. 31, Proc. So. Dakota Acad. Sci., No. 111-15 (1952); C.A. 48, 8675. (19G) Oriental Chemical Food Co., Japan Patent 154,442 (Dec. 26, 1942); C.A. 44, 3013.
1 336
f
Oxid a tion, Halogenation, and General Applications Product andlor Method Application Levulinic acid peroxide Action of ozone and rubber. HrOa on acetyl levulinic acid Methyl ethyl ketone Levulinic acid and K2S208 Succinic acid Levulinic acid, air, VZOS,375' Succinic acid and acetone Levulinic acid, HzOZ,and Cu 1,4-Butanediol dinitrates, butane- Pb anode oxidation of levulinic acid triols Methyl vinyl ketone Levulinic acid at 450-650" over catalysts Acetoacrylic acid esters Levulinic acid esters with SeOz
Malonic acid Glutarimide Stability of solutions upon heating Phenylacylacetone, diphenylvaleric acid, and others Succinic acid 3-Bromolevulinic acid, 3-chlorolevuIinic acid. For acetoacrylic acid 3-Bromolevulinic acid, 2,3-dibromolevulinic, 3,5-dibromolevulinic, and tribromolevulinic acids Catalysis of ferrous ion with peroxide Sterilizing action of levulinic acid Effect on Monilia murmanica Stimulation of root formation Safety of use in foods Liquid-liquid extraction of hydrocarbons for separation of aromatics Biologically inactive derivative of riboflavin Polarographic studies Levulinate ion in immunochemistry Identification in paper chromatography Solvent for resins of pepper Corrosion when used for cleaning Mold retardant in coating of food containers Behavior as aerial disinfectant Heat-setting resins Hard rapid-cure resins
Ozone on levulinic acid (NH&)zSx,S, and levulinic acid Rate of bromination of levulinic acid Levulinyl chloride, AlC18, and benzene 5-Chlorolevulinic acid and " 0 3 Levulinic acid in HCl with Brp or Cln Various conditions
On Passzjora sp. and Bignonia sp. Rats, guinea pigs, chicks At 200-250' F. countercurrent. H y drolysis of lactone formed
Fusion of levulinic acid and urea Formaldehyde reaction with keto acid esters
(20G) Overend, W. G., Turton, L. M., Wiggins, L. F., J . Chem. Soc. 1950, 3500-5; C.A. 45,6640. (21G) Ponsford, A. P., Smedley-MacLean, I., Biochem. J . 28, 892-7 (1934); C.A. 29, 123. (22G) Pummerer, R., Ebermayer, G., Gerlach. K.. Ber. 64B. 804-9 (1931); 'C.A.'25, 4438. ' (23G) Raymond, S., J . Am. Chem. Soc. 72, 3296-7 (1950). (24G) Raymond, W. F., Med. Research Council (London), Spec. Rept. Ser. 262, 87-9 (1948); C.A. 43, A708
(25G) Shokai,' E. C., Devlin, P. A. (to
INDUSTRIAL AND ENGINEERING CHEMISTRY
Shell Development Co.), U. S. Patent 2,488,883 (Nov. 22>1949). Siegel, hl., Pressman, D., J . Am. Chem. SOC.76, 2863-6 (1954). Tetsumoto, S., J . Agr. Chem. SOC. Japan 13, 1159-64 (1937); C.A. 32, 1739. Tischer, R. G., Fellers, C. R., Doyle, B. J., J . Am. Pharm. Assoc. 31, 217-20 (1942); C.A. 5565. Traub, H. P., Proc. Am. Soc. Hort. S C ~35, . 438-42 (1938); C.A. 32, 7518. Wieland, H., Franke, W., Ann. 457, 1-70 (1927); C.A. 22, 1065.
b lactams and Related Compounds T h e 4-amino derivatives of levulinic acid readily form lactams a n d 5-methylpyrrolidones (5-me thylpyrrolidinones) (Figure 1). T h e amides upon hydrogenation of the keto group also form 5methylpyrrolidones. Under certain conditions the amides will lactamize to 5methylpyrrolones (5-methylpyrrolinones) (Figure 1). I t is probable that the levulinamides exist largely i n the pseudo form (7323). In general, the yields of many of these derivatives are high, 7570 of theory or more. References ( 1 H ) Dunlop, A. P., Sherman, E. (to Quaker Oats Co.), U. S. Patent 2,681,349 (June 15, 1954). (2H) Floyd, D. E. (to General Mills, Inc.), Ibid., 2,610,212 (Sept. 9, 1952). ( 3 H ) Glenn, 'H. J., Friefelder, M., Stone, G., Hertz, E., J . Am. Chem. SOC. 77, 3080-2 (1955). (4H) Hachihama, Y., Hayashi, I., Technol. Repts. Osaka Uniu. 4, 173-9 (1954): C.A. 49, 6226. (5H) Haskelberg, L., J. Am. Chem. SOC. 70, 2830-1 (1948). 16H) Havashi. I.. Hachihama, Y., J . Chem.'Soc.. Jafian, Ind. Chem..Sect. 57, 127-9 (1954); C.A. 49, 11554. (7H) Hoffmann-La Roche & Co., F., A.G., Ger. Patent 609,244 (Feb. 11, 1935); C.A. 29, 3116. (8H) Horning, E. C., ed., "Organic Syntheses," vol. 3, p. 328, Wiley, New York, 1955. (9H) Kueter, K . E., Richards, R. K., J . Pharm. Exfitl. Therap. 106, 402 (1952). (10H) Lukes, R., Chem. Lis@ 22, 1-12 (1928); C.A. 22, 1773. (11 H ) Lukes, R., Collection Czechoslou. Chem. Communs. 1, 119-36 (1929); C.A. 23, 4469. ~I
f
Product and/or Use
1,5-Dimethy1-2-pyrrolone l-Phenyl-5-methyl-2-pyrrolidone
1-p-Tolyl-5-methyl-2-pyrrolidone 1,5-Dimethy1-2-pyrrolidone 5-Methyl-2-pyrrolidone
1-p-Ethoxyphenyl-5-methy1-2pyrrolidone. Medicinal 5-Cyano-5-methyl-2-pyrrolidone. Analgesic 1-Vinyl-5-methyl-2-pyrrolidone. Polyvinylmethylpyrrolidone 1-Benzoyl-, 1-ethyl-, 1-ethanol-, and 1-chloroethyl-5-methylpyrrolidone n-Octyl-, 2-ethylhexyl-, dodecyl-, ethyl-, butyl-, and benzyl esters of 5-carboxy-5-methyl-2-pyrrolidone. Poly( vinyl chloride) plasticizers 1-( 3-Hydroxypropyl)-5-methyl-2pyrrolidone 1-Ethvlene bis-(5-cvano-5-methv1-2pyrrolidone) . ' Levulinic acid diethvlamide, levulinic acid dibut ylamide
Method
a-Angelica lactone and methylamine Levulinic anilide and toluidide, Hz, and Pd Levulinic acid, methylamine, Hz, and Ni HI, and Levulinic acid, CH20, "3, Ni Levulinic acid, NHIOH, "2, and Ni y-Valerolactone and ZnClz. 6"s Ethyllevulinate, $-phenetidine, Hz, Ni 5-Methylpyrrolidone-2 and CzHn, 1(2-hy+-oxyethyl)-5-methyl-2pyrrolidone
(SH, 74H) By Strecker's synthesis
(77W
Ethyl levulinate, propanolamine, Hz, and Pt Methyl levulinate, HCN, ethylenediamine, and catalyst Levulinic acid and diethylamine, ychlorovalerolactone and diethylamine 4-Hydroxyvaler yldiethylamide Hz on levulinyldiethylamide (5H) Levulinic acid, "3, and Ni (2H) 4-Aminovaleric acid Levulinic acid, ",OH, He, and Ni ( 7 5 H ) 2-Amino-2-methylglutaric acid and ( 77H) derivatives Ethyl-4-cyano-4-hydroxyvalerate Ethyl levulinate, NaHS03, and (3H) NaCN; and dimethylamine Ethyl-4-cyano-4-dimethylamino-
cerate
(12H) Lukes, R., Prelog, V., Collection Czechoslov. Chem. Communs. 1, 617-23 (1929); C.A. 24, 1374. (13H) Lukes, R., Prelog, V., Chem. Listy 24, 251-3 (1930); C.A. 24, 4762. (14H) Moffett, R. B., J . Org. Chem. 14, 862-7 (1949).
b a-Angelica
J (15H) Nakamura, S., Ashida, K.: J . Agr. Chem. SOC. Japan 24, 185-7 (1950); C.A. 47, 3239. (16H) Spath, E., Lintner, J., Ber. 69B, 2727-31 (1936); C.A. 31, 2172. (17H) Takenishi, T., Simamura, O., Bull. Chem. SOC. Japan 27,207-9 (1954); C.A. 49, 8245.
lactone
Dehydration of levulinic acid occurs upon distillation and a-angelica lactone (7-lactone of 4-hydroxy-3-pentenoic acid) is formed (91) together with some 0angelica lactone (7-lactone of 4-hydroxy2-pentenoic acid). Better yields are obtained when the levulinic acid is distilled at low temperatures with a catalytic amount of phosphoric acid (51). a-Angelica lactone behaves as the anhydride of levulinic acid, particularly the pseudo or cyclic form of levulinic, a n d as a substituted vinyl ester. I t possesses an active methyl group. Some of its reactions are shown i n Figure 1. References Storage tanks and some of the equipment used in the initial production of levulinic acid
\
Lactams and Related Compounds
(11) Auwers, K. v., Ber. 56B, 1672-82 (1923); C.A. 18, 61. (21) Cavallito, C . J., Haskell, T. H., J . Am. Chem. SOC. 67, 1991-4 (1945). (31) Eskola, S., Sode, K., Leppamaki, E.,
(41) (51) (61)
(71)
(81) (91) (101)
Rinne, I., Suomen Kemistilehti 28B, 87-9 (1955); C.A. 49, 7494. Friedman, L., Long, F. A., J . Am. Chem. SOC. 75, 2832-6 (1953). Helberger, J. H., Ulubay, S., Civelekoglu, H., Ann. 561, 215-20 (1949); C.A. 43, 4646. Jacobs, W. A., Scott, A. B., J . Biol. Chem. 87, 601-13 (1930); C.A. 24, 5721. Kaltschmitt, H., Tartter, A. (to Badisch Aniline und Sodafabrik), Ger. Patent 804,567 (April 25, 1951); C.A. 45,8031. Kirkland, E. V., Reynolds, C. A., VanderWerf, C. A., J . A . Chem. SOC.72, 1764-8 (1950). Kuehl, F. A., Linstead, R. P., Orkin, B. A., J . Chem. Soc. 1950, 2213-8; C.A. 45, 3328. Lukes, R., Syhora, K., Collection Czechoslou. Chem. Communs. 19, 1205-14 (1954); C.A. 49, 4518.
VOL. 48, NO. 8
AUGUST 1956
1337
(111) Marrian, D. H., Russell, P. B., J . Chem. SOL.1946, 753-4; C.A. 41, 113. (121) Marrian, D. H., Russell, P. B., Todd, A. R., Biochem. J . 45, 533-7 (1949); C.A. 44,8863. (131) Marvel, C. S., Levesque, C. L., J . Am. Chem. Soc. 61, 1682-4 (1939). (141) Oettingen, W. F., Zbid.: 52, 2024-5 (1930). (151) Oettingen, W. F., J . Phurmucol. 39, 59-69 (1930); C.A. 24, 5381. (161) Oettingen, W. F., J . Pharmucol. 36, 335-54 (1929); C.A. 24, 1156; see also C.A. 36, 4197; 38, 4684; 41, 1727, 1757, 3212; 43, 1110, 7138; 44,9057; 45, 9717-8; 46, 4484, 8802, 9766; 48, 8945. (171) Rasmussen, R. S.,Brattain, R. R., J . Am. Chem. Soc. 71, 1073-9 (1949). (181) Smets, G., Medeleel. Vlaam. Chem. Ver. 7, 95-108 (1945); C.A. 41, 3317. (191) Walton, E., J. Chem. Soc. 1940, 43842; C.A. 34, 5078.
f Product and/or Use
Reactants or Method
Structure a-Benzal-a-angelica lactone ; salicylal-, a-Angelica lactone and aldehyde resorcylal-, anisal-, vanillal-, piperonal-, p-hydroxybenzal-, m-hydroxybenzal-, 3,4-dihydroxybenzal-, p-acetamidobenzal-, p-aminobenzal-, cinnamylal-, and furfurylidene-. For muscular depressants, anthelmintics, and eelworm hatching agents Cardiac effects Valeric acid a-Angelica lactone, HP,and Pt Poly-a-angelica lactone a-Angelica lactone and BFB 1-Phenyl-5-hydroxy-5-methyl-2-pyrroli- a-.4ngelica lactone and aniline done a-Angelica lactone and cysteine, Mechanism of antibiotic action homocysteine, and p-aminoethanethiol 2-Hydroxy-3-acetonylcoumarin a-.4ngelica lactone and salicylaldehyde Methyl vinyl ketone or-Angelica lactone at 570" on Si02 Pseudo esters of levulinic acid a-Angelica lactone and alcohols Levulinamide and levulinanilide a-Anqelica lactone and NHI or aniline a-Angelica lactone, Ha, and Cu1,4-Pentanediol and y-valerolactone Ba- Cr Peroxide of a-angelica lactone PolaropraDhic studv Infrarcd s'pectra ' Halogenated acid halide Mass spectra a-Angelica lactone and KzC03 Dimer of a-angelica lactone 3,3-Diacetylpropionic acid a-Angelica lactone, Ac2O and BFa 3-Bromolevulinyl bromide. For aceto- @-Angelicalactone and Brz acrylic acid and protoanemonin
\
Installation for the manufacture o f calcium levulinate
1338
INDUSTRIAL AND ENGINEERING CHEMISTRY
\
a-Angelica Lactone Ref
I
(71,721) ( 741, 751)
( 761)
(61) ( 731) (781,791) (21)
( 7 71)
(2G) (37C) (51)
(51) (81) (77Z)
(71) (41) (701)
(31) (9K, 77K)
. . ..
b @-Angelica Lactone ,
@-Angelica lactone is formed simultaneously with a-angelica lactone during the slow distillation of levulinic acid (Figure 1). It is reportedly formed by heating a-angelica lactone with diethylaniline hydrobromide (7.24). @Angelica lactone resembles maleic anhydride i n structure ( 7 4 . T h e dimer of 6-angelica lactone ( 9 J ) (Figure l), may be the same as the dimer of a-angelica lactone (7011, since melting Points for a t least one of the Wolff and Moyer ( 9 J ) dimers a n d one of their dimer acids agree with the respective compounds of Lukes a n d Syhora ( I O Z ) . T h e bases used to prepare the dimers also cause isomerization of the angelica lactones, so that either lactone may yield the Same dimer. References
(1J ) Auwers, K. v., Harris, L., Ber. 62B, 1678-88 (1929); C.A. 24,68. (25) Coover, H. W., Dickey, J. B. (to Eastman Kodak Co.), U. S. Patent 2,652,416 (Sept. 15, 1953). (3J) Eskola, S., Udd, K., Leppanen, K., Stjernvall, G., Suomen Kemistilehti 20B, 13-6 (1947); C.A. 42, 1192.
f
@-AngelicaLactone Reactants or iMethod Structure Min. fatal dose, 0.7-1.25 g./kg. Cats Cress seeds Inhibition of Plants Bean seedlings Dimer of 0-angelica lactone. For plasti- 8-Angelica lactone and NaOMe or other bases cizers for films, and coatings (4-( ~-Valerolactone-3)-4-methylbuten-2ollde) Methyl vinyl ketone &Angelica lactone at 570" on Si02 Cardiac effects Lactone acids from @-angelica lactone dimer [4-(5-0~0-2-methyltetrahydro-3furyl)-2-penten-4-ol-l-oic acid] Polarographic study ~ ~ ~ ~ e o ~ f , [ ~ Seed ~ potatoes, ~ ~ 1-naphthaleneacetic ~ a acid, and 0-angelica lactone Halogenated acid halide Mass spectra Infrared spectra Diethyl-or-methylene-r-carboethoxy@-Angelicalactone, triethylpropane phosphonate (?) phosphite, and HzSOd Product and/or Use
g::zbitor
Ref. (71)
(6J) (5J) (4J) (3J,9 J ) (701, 705) (2G) ( 750 ( 701, 77J)
(81) (8J) (71)
(41) (75)
(25)
\
(4J) Gandini, A., Atti accad. ligure SCI. 5, 316-24 (1949); C.A. 44, 9006. (5J) Haynes, I,. J., Jones, E. R. H., J. Chem. SOC.1946, 954-7; C.A. 41, 705. (6J) Oettingen, W. F. v., Garcia, F . , J. Pharmacol. 36, 355-62 (1929); C.A. 24, 1156. (75) Rosenkrantz, H., Cut., M., Helv.
7,
J
Chim. Acta 36, 1000-3 (1953); C.A. 47, 11988. (85) Veldstra, H. (to N. V. Amsterdamsche Chininefabrick), U. S. Patent 2,544,243 (March 6, 1951). ( 9 J ) Wolff, H., Moyer, W. W. (to A. E. Staley Mfg. Co.), Zbid., 2,493,373 (Jan. 3. 1950). (1OJ) Ibid., 2,493,374 (Jan. 3, 1950). ( l l J ) Ibid., 2,493,375 (Jan. 3, 1950).
b Heterocyclic Compounds Derived from Levulinic Acid Various heterocyclic compounds are included in the preceding discussion. T h e critical review and discussion by Morton ( 7 7 4 deal thoroughly with this subject. Compounds mentioned above are a pyrone (33F), a dioxane (77F),a coumarin ( 7 7Z), and some thiazocines (?) (ZZ). Proposed uses are as bacteriostatic and analgesic agents.
f
References
(1K) Asahina, y., Fujita, A., Acta Phytochim. (Japan)1, 1-42 (1922); C.A. 17, 1465. (2K) Baer, H., Holden, M., Seegal, B. C . , J . Biol. Chem. 162, 65-8 (1946); C.A. 40, 2190; see also C.A. 32, 4669; 41, 2463; 42, 3793; 46, 1102; 47,7094.
Heterocyclic Compounds from Levulinic Acid Product and/or Use Method Protoanemonin; y-hydroxyvinylacrylic 0-Bromolevulinic acid, Ac20, and acid lactone NaOAc. Isolation and structure From a-angelica lactone, Br2 and quinoline Antibacterial action of protoanemonin Inhibition of plant growth by protoanemonin Ethyl-4-methylthiazole- 5-acetate Thioformamide and ethyl 0-bromolevulinate 5-Ethoxy-2-methylthiophene Levulinic acid, alc. HCl, and HzS Ethyl-2-p-sulfamylphenylamino-4Ethyl-0-bromolevulinate and sulfmethyl thiazole-5-acetate amylphenylthiocarbamide Thiotolenol Levulinic acid and PZSS 4,5-Dihydro-6-methyl-3-pyridazone. Ethyl levulinate and hydrazine Derivatives show bacteriostatic hydrate activity Critical review and discussion on heterocycles from levulinic acid 2-Phenyl-6-methyl-3-pyridazinone. Phenylhydrazone of levulinic acid For bacteriostatic activity 2-Methyl-3-indoleacetic acid, methyl Phenylhydrazone of Xevulinic acid ester. For plant growth hormone with HzS04 2-m-Tolyl-6-methyl-3-pyridazinone. m-Tolylhydrazone of levulinic acid For analgesic 2-Amino-4-methyl-5-thiazoleacetic Ethyl-0-bromolevulinat e and thiourea acid, ethyl ester. For bacteriostatic activity 2-Methyl-7-nitro-3-indoleacetic acid. o-Nitrophenylhydrazone of ethyl levAlso 7-chloro-, 5-chloro-, and 5,7ulinate with ZnCln and HCI. Also dichloro- derivatives. For plant respective hydrazones growth hormone 1,6-Dimethy1-3-pyridazinone Ethvl levulinate and methylhydrazine sulfate
L
\
Ref. ( 7K, 77K, 78K) ( S K , 77K)
(2K) (20K)
(4K, 5 K ) (6K) (7K) (7 2 ~ ) ( 75K)
(77'4) ( 76K) ( 73K)
( 70K)
(8K)
(3K, 79K)
( 74K)
J
(3K) Bauer, H., Strauss, E., Ber. 65B, 308-15 (1932); C.A. 26, 2739. (4K) Buchman. E. R.. Sarnent. H.. J . Am. Chem. SOC.'67. 355-9 (1 945 ). Cerecedo, L. P., Tolpin, J. G., Ibid., 59, 1660-1 (1937). Chakrabarty, N. K., Mitra, S. K., J . Chem. SOC. 1940, 1385-7; C.A. 35, 741. Ganapathi, K., Proc. Indian Acad. Sci. lZA, 274-83 (1940); C.A. 35, 1772. (8K) Gregory, H., Wiggins, L. F., J. Chem. SOC.1947, 590-2; C.A. 41,
. ,
5865
(9K) Grundmann, C., Kober, E., J. Am. Chem. SOC.77, 2332-3 (1955). (10K) Haworth. W. N.. Wiwins. L. F.. Brit. Patent 656,225- (Aug. 15; 1951); C.A. 46, 7593. (11K) Kipping, F. B., J. Chem. SOC.1935, 1145-7; C.A. 29, 7278. (12K) Mentzer, C., Billet, D., Bull. sot. chim. 12, 292-5 (1945); C.A. 40, 2828. (13K) Mitsui, T., J. Agr. Chem. SOC. Jaban24,465-71(1950-51); C.A. 47; 9301. (14K) Overend, W. G., Turton, L. M., Wiggins, L. F., J . Chem. SOC. 1950. 3500-5: C.A. 45, 6640. (15K) Overen'd, W. G., Wiggins, L. F., J . Chem. SOC. 1947, 239-44; C.A. 41, 5132. (16K) Overend, W. G., Wiggins, L. F., J . Chem. SOC. 1947, 549-54; C.A. 41, 5527. (17K) Sakuma, A., J . Pitarm. SOC.Japan 73, 1137-9 (1953); C.A. 48, 12070. (18K) Shaw, E., J . Am. Chem. SOC.68, 2510-3 (1946). (19K) Stevens, F . ~J., Fox, S. W., Ibid., 70, 2263-5 (1948). (20K) Thimann, K. V., Bonner, W. D. Proc. Natl. Acad. Sci. U. S. 35, 272-6 (1949); C.A. 43, 8462; see also C.A. 43, 2675, 5830. VOL. 48, NO. 8
AUGUST 1956
1339
Experimental Table I. Reactant
...... Hydrogen Butanol Hydroxylamine Formaldehyde Furfural
. ....
Cyclopentadiene Hydrogen, electrolytic hTitrosylchloride Dimethylamine and formaldehyde Ammonia and hydrogen Methylamine and hydrogen Aniline and hydrogen Ethanolamine and hydrogen Ethylenediamine and hydrogen Methylamine Sodium cyanide Methyl levulinate and HCN Methyl levulinate and Clz Methyl levulinate and Mg-Hg Ethyl levulinate
4- NaOEt
+
Ethyl levulinate hydrazine Ethyl levulinate f phenylhydrazine
Reactions of Levulinic Acid
1 340
>
Product a-Angelica lactone yvalerolactone Butyl levulinate Levulinyl oxime ? up to 2.5 moles added /3-Furfurylidene levulinic acid 8-Furfurylidene levulinic acid Cyclopentadienylidene valeric acid ?, neut. eq. 190 Valeric acid 6-Chloroisonitrosolevulinic acid 6-Dimethylamino- -/-oxocaproic acid 5-Methyl-2-pyrrolidone 1,5-Dimethyl-2-pyrrolidone l-Phenyl-5-methyl-2-pyrrolidone 1-( P-Hydroxyethyl)-5-methyl-2pyrrolidone 1-(P-Aminoethyl)-5-methyl-2p yrrolidone 1,2-Dimethylpyrrolone -pCyanovalerolactone 7 -Cy anovalerolactone
Laboratory Yield, % Theory 80 93 94 83
Methyl-3-chlorolevulinate
4-Carboxy-l-methyl-l,3-~yclopentadiene-3-propionic acid 4-Carboxy-l-methyl-l,3-~yclopentadiene-3-propionic acid 6-Methyl-3-pyridazinone 2-Phenyl-6-methyl-3-pyridazinone
T h e experimental work was conducted with technical levulinic acid derived from cellulose. This material is best characterized by a freezing point between 25' and 28' C.; it assays 95y0or higher and usually contains 2 to 39;; lactone and u p to ly0water. I t is very difficult to distill levulinic acid which does not contain traces of lactones and water. By repeated crystallization material can be prepared which assays over 997G a n d freezes a t 30.5' C. An averaged molecular depression of the freezing point of 5.37 and a pK, of 4.5 have been determined. Salts of levulinic are not oil-soluble. T h e suggested use of sodium levulinate as a n antifreeze (76A) was checked; the lowest freezing point, -16.5' C., was found with aqueous 3M solution. Esters. Esters of levulinic acid are easy to make with monohydric alcohols (2L); butanol is the example shown in Table I. Vinyl levulinate was prepared by transesterifying levulinic acid with a n excess of vinyl acetate in the presence of a trace of sulfuric acid with a n d without the presence of mercury salts (4L). Vinyl levulinate, which has not previously been reported, is a colorless liquid with a n odor reminiscent of green apples; boiling point 93' a t 17 mm., refractive index 1 . 4 3 8 8 ~a~n, d density 1.031ii. I t has not been possible to induce polymerization of vinyl levulinate itself. However, a copolymer with vinyl levulinate was prepared by emulsion polymerization of 80% vinyl chloride, 20% vinyl levulinate, 0.3y0benzoyl peroxide,
cellulose levulinates could be formed, but does not describe them (3L). Several types of cellulose acetate-levulinate preparations have been made by ester interchange of cellulose acetate and 90% levulinic acid a t 100' C. Depending upon the length of time which the mixture is held a t 100' C., preparations ranging from 1.5% levulyl and 3.8y0 acetyl to 19.370 levulyl and 9.&y0 aceiyl groups can be obtained. The longer intervals induce some hydrolysis of the acetyl groups and possibly a lowering in cellulose chain length. A cellulose acetate-levulinate, 34.8% acetyl and 2.87$ levulyl, showed a tensile strength of a cast film '/? inch wide of 4.6 pounds pel mil, compared to 1.8 for the untreated cellulose acetate. Another product, &.1% acetyl and 12.4y0 levulyl. was soluble i n cold water and insoluble in acetone. Tests indicated that this water-soluble cellulose acetate-levulinate possessed antisoil redeposition activity as we11 ds emulsifying activity in oil-water systems. Considerable variations in properties of the celluIose acetate-levulinate can result from different grades of cellulose acetate with different degrees of levul) 1 content, T h e introduction of a keto crouD into polymers by means of levulinic acid appears to supply internal and increase in tensile strength. Results of preliminary tests indicate th3t good stability to weathering. useful solubility changes, and dyeing assistance are obtained in levuJinate-containing polymers, Reactions of Levufinic Acid. Some typical reactions were conducted with technical Ievulinic acid and the yields arc summarized in Table I. Levulinic acid dehydrates readily to @-angelica lactone, although the catalytic method with Phosphoric acid is Preferred for 1aboratorY work (51). Table I gives the method employed for laboratory preparations. Of particular interest are reactions on the number 5 carbon, which yielded 6-furfurylidenelevulinic acid, 6-
..
39 6 66 40 13 31 87 64 10 60 42 9
15 60 57 28 67 62 96
and Aerosol MA in water a t 45' to 55' C. for 72 hours' The product contained
3'3% levulyl groups' The strength Of a cast ' / 4 inch wide showed 3.7 pounds per mil; a copolymer Of 476 acetate in showed with identical treatment 2.2 pounds per mil. A copolymer of acrylonitrile and vinyl levulinate containing 15.3yo levulyl groups was prepared with 80% acrylonitri~e-2070 vinyl levulinate in an ~~~~~~lMA emulsion in the presence of ammonium persulfate, ammonium bisulfite, and potassium dihydrogen phosphate. Copolymers with styrene could not be formed with either potassium persulfate or benzoyl peroxide catalysts. T h e patent literature implies that Table II.
I
Reactions of a-Angelica Lactone
Laboratory Method Yield, 70 EmReactant Product Theory ployed Water ( H + ) Levulinic acid 99 ( 72A 1 Ammonia Pseudo-levulinamide 72 (5151) Author's Glycerol ( H +) Trilevulin, sap. eq. 132 39 Ethylhexanol ( H Ethyl hexyl levulinate, b.p. 129 (9 mm.) 82 (37C) Phenol ( H + ) Phenyl levulinate, b.p. 125-135" ( 5 mm.) 66 (37C) Isopropyl alcohol ( H +) Pseudo-isopropyl 1evuli;ate 72 (37C) Author's Nitrosyl chloride ?, crystalline, m.p. 87.5 72 Author's Ethylenediamine ?, dark resin .. Author's .. Formaldehyde (OH-) ?, crystals, m.p. about 250", 127 eq. wt., or resin Furfural ( O H -) 2-Furfurylidene-4-methyl-A3,4-butenolide 42 ( 721) Vanillin (OH-) 2-Vanyllidene-4-methyl-43,4-butenolide 65 ( 721) Chlorine and methanol Methyl 3-chlorolevulinate, b.p. 209-210 92 (GK! Author's Hydrogen cyanide y- Cyanovalerolactone 65 [Hg(Ac)z1 Hydrogen chloride Pseudo-levulinyl chloride: b.p. 149' (11 ( 724 mm.)
INDUSTRIAL AND ENGINEERING CHEMISTRY
Table 111.
Properties of Solvents from Levulinic Acid cy-
Molecular weight Density Freezing point, O C. Solubility in water, yo Boiling point, ’ C. 10 mm. 100 mm. 400 mm. 760 mm. Specific gravity, z b / d Refractive index, 25 Flash point, O F.
P-
Y-
Angelica Lactone 98.1 1.083 17.9 3
Angelica Lactone 98.1 1.082 Ca. -30 100
Valerolactone 100.1 1.044 Ca. -24 100
51.8 104.6 152 169 1.083 1.445 152
83.1 141 185 208 1.082 1.455 210
79.8 136,5 182.3 207.5 1.044 1.430 201
chloroisonitrosolevulinic acid, and edimethylamino-y-oxocaproicacid. However, none of the yields obtained here for the 5-carbon are industrially significant. Formaldehyde reacts readily with alkaline solutions of levulinate, but the products are not identified. Reactions of a-Angelica Lactone. T h e simplest and most reactive derivative of levulinic acid is a-angelica lactone. I t is an unsaturated lactone which reacts a s a lactone, as the anhydride of levulinic acid, and as an active methylene compound. Reactions as the anhydride lead frequently to pseudo compounds. Yields of some typical reactions are summarized in Table 11. With materials such as water, alcohol, ammonia, hydrochloric acid, and hydrogen cyanide the pseudolevulinyl compounds are usually obtained. T h e nature of the catalysts when used is shown in parentheses in Table 11. T h e formation of trilevulin is an example wherein the pseudo ester was not obtained. A mixture of 0.5 mole of glycerol, 1.5 moles of a-angelica lactone, and 0.1 gram of toluenesulfonic acid was warmed to 80°,whereupon an exothermic seaction heated the mixture to 200’ in 30 seconds. T h e mixture was cooled to 170’ a n d allowed to stand several hours. I t was then poured into ice water, extracted with benzene, washed with sodium carbonate solution, and dried, a n d the benzene was evaporated. The neutral product was obtained, as shown in Table 11. T h e pseudo ester can be converted to normal esters, ethyl hexyl and phenyl, by either heating a t temperatures above 200’ or using a n acid catalyst. Of possible interest is the reaction of chlorine to yield a pseudo-3-chlorolevulinyl chloride. This material reacts rapidly with water, methanol, or other alcohols to give the corresponding 3chlorolevulinates. The principle can be used to obtain good yields of 3-halolevulinates, which are difficult to prepare by other means. Methyl acetoacrylate, 70% theory, is obtained from methyl-3chlorolevulinate and sodium acetate.
M1. Acetylene Per M1. Solvent
Solvent Dimethylpyrrolidone 113 2 0.995 Below -70 100
... ... ... 216 0.995 ... ...
Solvents from Levulinic Acid. Either a-angelica lactone or levulinic acid hydrogenates to 7-valerolactone. aAngelica lactone will isomerize ther-
Table IV. Comparison of Lactones as Solvents for Vinylite Resin yo Solvent Required in Thinner to Give Equal Fluidaty 20%
Solveh solids Methyl isobutyl ketone 47 Isophorone 31 or-Angelica lactone 21 P-Angelica lactone 19 7-Valerolactone 24
15%
solads 26 19 14 13 15
mally, but not so well, by the classical method (724, to P-angelica lactone. Thus there are three lactones derived from levulinic acid (Figure 1). I n addition, 1,5-dimethy1-2-pyrrolidoneexhibits excellent solvent properties. T h e properties of the four solvents are shown in Table 111. A simple way of demonstrating the relative stability of these lactones is by acid hydrolysis. Comparison with each other and with methyl levulinate was made by hydrolysis with 0.33N hydrochloric acid in aqueous solutions for 4 minutes a t 100’ C. Under these conditions a-angelica lactone is 98% hydrolyzed; &angelica lactone, 7%; yvalerolactone, 5%; and methyl levulinate, 13y0. These solvents are miscible with many common organic liquids and with the exception of a-lactone are miscible with water. All or some of the four materials will dissolve such types of materials as ethylcellulose, nitrocellulose, polystyrene, vinyl resins, saran, methacrylate interpolymers, maleic resins, Epon resins, some modified phenolic resins, Dynel, Acrylan, and terpene resins. For comparative purposes the solubility of acetylene a t atmospheric pressure and room temperature was determined. Results were as follows:
a-Angelica lactone p-Angelica lactone y-Valerolactone 5-Methyl-2-pyrrolidone
16.3 15.5 15.6 18.6 1,5-Dimethy1-2-pyrrolidone 32.2 Dimethylformamide 26.7 Dimethylpyrrolidone was the best acetylene solvent and was slightly superior to dimethylformamide. T h e a- and P-angelica lactones a n d yvalerolactone were examined as solvents for vinyl resins in comparison to methyl isobutyl ketone and isophorone. Vinylite V Y H H resin was dissolved in the various solvents and toluene was added as diluent to points of equal viscosity. Thus a figure was obtained for per cent solvent required in thinner to give equal fluidity. Results are shown in Table IV. Both P-angelica- a n d y-valerolactone are miscible in water.
Summary Substitution of levulinic acid for a portion of the acetyl groups in vinyl acetate-containing resins and cellulose acetate yields materials of increased strength. a-Angelica lactone, one of the simplest products to be made from levulinic acid, can be converted to a series of pseudolevulinic acid derivatives and provides a means of obtaining S-chlorolevulinic acid. I t is convertible to both 0-angelica lactone a n d 7-valerolactone. T h e three lactones and dimethylpyrrolidone derived from levulinic acid are good solvents. T h e exceptional reactivity of levulinic acid and its lactones coupled with its raw material source would seem to provide a n ideal set of conditions for the use of levulinic acid as a basic chemical raw material.
Acknowledgment T h e author acknowledges the technical assistance of Carl Bordenca and staff of the Southern Research Institute. References (1L) McElvain, S. M., “Characterization of Organic Compounds,” p. 198, Macmillan, New York, 1946. (2L) Micovic, V. M., Bull. sod. chim. (5) 4, 1661-9 (1937); C.A. 32, 1241. (3L) Staud. C. J.. Webber. C. S. (to Eastman Kodak C O . ) , ’ S. ~ .PatGnt 1,900,871 (March 7, 1933). (4L) Toussaint, W. J., MacDowell, L. G. (to Carbide and Carbon Chemicals Gorp.), Zbid., 2,299,862 (Oct. 27, 1942).
. ,
RECEIVED for review December 27, 1955 ACCEPTED March 9, 1956 Division of Industrial and Engineering Chemistry, 129th Meeting, ACS, Dallas. Tex., April 1956. VOL. 48, NO. 8
AUGUST 1956
134 1
