Organic Syntheses Collective Volume 3

Organic Syntheses, Coll. Vol. 3, p.1 (1955); Vol. 24, p.1 (1944).

ACENAPHTHENEQUINONE

Submitted by C. F. H. Allen and J. A. VanAllan. Checked by L. Matternas, H. Lloyd, and E. C. Horning.

1. ProcedureA mixture of 100 g. (0.65 mole) of a technical grade of acenaphthene, 5 g. of ceric acetate (Note 1), and 800 ml. of glacial acetic acid is placed in a 4-l. stainless-steel beaker arranged for external cooling with cold water (Note 2). A thermometer and a powerful stirrer are inserted, and 325 g. (1.1 mole) of sodium bichromate dihydrate is added over a period of 2 hours, the temperature being kept at 40 (Note 3). Stirring is then continued at room temperature for an additional 8 hours; during this time the reaction mixture becomes quite thick, owing to the separation of the quinone and chromium salts. The suspension is diluted with 1.5 l. of cold water, and the solid is collected on a 10-in. Bchner funnel and washed free from acid. The solid is next digested on the steam bath for 30 minutes with 500 ml. of a 10% sodium carbonate solution, and is filtered and washed. The solid is then extracted for 30 minutes at 80 with 1 l. of 4% sodium bisulfite solution; at the end of this period 15 g. each of Filtercel and Norit are added, and the suspension is filtered. The extraction is repeated, and the combined filtrates are acidified at 80 with constant stirring (Note 4), to Congo red paper, with concentrated hydrochloric acid (5060 ml.). The temperature is maintained at 80 for 1 hour with constant stirring. The acenaphthenequinone separates as a bright yellow crystalline solid; it is collected on a Bchner funnel and washed with water until free from acid. The yield is 4570 g. (3860%); m.p. 256260. The crude quinone (50 g.) is recrystallized from 250 ml. of o-dichlorobenzene without filtering (Note 5); the crystals are rinsed with methanol. The recovery is 45 g., m.p. 259260 (Note 6), (Note 7).

2. Notes1. The checkers used Eastman Kodak white label acenaphthene. Cerium salts appear to have a beneficial effect. Probably any cerous salt will be satisfactory, it being oxidized in the reaction. The submitters have used cerous chloride, ceric carbonate, and ceric acetate; the last can be obtained in the form of a 50% mixture with other rare-earth acetates from the Lindsay Light and Chemical Company, West Chicago, Illinois. The checkers used cerous chloride. 2. The checkers found no need to cool the reaction; instead the bath was used to heat the reaction to 40. With technical grade acenaphthene, cooling is necessary. 3. If the oxidation temperature has been allowed to rise to 50, tar formation makes it necessary to do five or six treatments with sodium bisulfite. The extractions should be continued as long as the filtrate gives a precipitate on acidification. 4. The acidification should be performed in a hood; much sulfur dioxide is evolved. 5. The quinone crystallizes so rapidly that filtration is impossible; however, there is no insoluble material if mechanical dirt has been excluded. 6. This oxidation has been run using 80 times these amounts; the yield of recrystallized material drops to 3840%. 7. The red color of acenaphthenequinone1 is due to biacenaphthylidenedione, m.p. 295. It is an appreciable contaminant in a hot oxidation; the product may also contain appreciable amounts of

naphthalic anhydride.

3. DiscussionAcenaphthenequinone has been prepared by oxidation of acenaphthene with chromic acid,1,2,3,4,5,6,7,8,9,10 with calcium permanganate,11 with air in the presence of catalysts in various solvents,12,13,14,15 with 30% hydrogen peroxide in acetic acid,16 by the formation of an oxime with an alkyl nitrite followed by hydrolysis,17,18,19 and from oxalyl chloride and naphthalene.20,21 This procedure is based on the disclosure in a P.B. report.10

References and Notes1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. Org. Syntheses, 24, 1 (1944). Graebe and Gfeller, Ann., 276, 4 (1893). Graebe and Gfeller, Ber., 20, 659 (1887). Graebe and Gfeller, Ber., 25, 654 (1892). Francescone and Pirazzoli, Gazz. chim. ital., 33, I, 42 (1903). Braun and Bayer, Ber., 59, 921 (1926). Dashevskii and Karishin, Org. Chem. Ind. U.S.S.R., 7, 729 (1936) [C. A., 31, 679 (1937)]. Kiprianov and Dashevskii, J. Applied Chem. U.S.S.R., 7, 944 (1934) [C. A., 29, 2530 (1935)]. Kalle and Co., Ger. pat. 228,698 (1910) [Frdl., 10, 198 (19101912)]. P.B. 73485, 1579. Morgan, J. Soc. Chem. Ind., 49, 420T (1930). Jaeger, Brit. pat. 318,617 (1928) [C. A., 24, 2145 (1930)]. Duckert, Arch. Sci. Phys. Nat., 15, 244 (1933) [C. A., 28, 1255 (1934)]. Paillard, Helv. Chim. Acta, 16, 775 (1933). Ger. pat. 428,088 (1926) [Frdl., 15, 394 (1928)]. Charrier and Moggi, Gazz. chim. ital., 57, 740 (1927). Reissert, Ber., 44, 1750 (1911). Cain, The Manufacture of Intermediate Products for Dyes, Macmillan Co., London, 1919, p. 242. B.I.O.S., 986, 9; P.B. 73377, 2201; P.B. 73719, 2588. Lesser and Gad, Ber., 60, 243 (1927). Lesser and Gad, Ger. pat. 470,277 (1928) [Frdl., 16, 518 (1931)].

Appendix Chemical Abstracts Nomenclature (Collective Index Number); (Registry Number)chromium salts hydrochloric acid (7647-01-0) acetic acid (64-19-7) methanol (67-56-1) sodium carbonate (497-19-8) sulfur dioxide (7446-09-5) sodium bisulfite (7631-90-5)

Norit (7782-42-5) chromic acid (7738-94-5) Naphthalene (91-20-3) hydrogen peroxide (7722-84-1) naphthalic anhydride (5343-99-7) acenaphthene (83-32-9) Acenaphthenequinone (82-86-0) ceric acetate sodium bichromate dihydrate (10588-01-9) cerous chloride (7790-86-5) biacenaphthylidenedione calcium permanganate oxalyl chloride (79-37-8) o-dichlorobenzene (95-50-1) ceric carbonateCopyright 1921-2005, Organic Syntheses, Inc. All Rights Reserved


ACENAPHTHENOL-7[1-Acenaphthenol]

Submitted by James Cason Checked by R. L. Shriner and Elmer H. Dobratz.

1. ProcedureA. Acenaphthenol acetate. In a 2-l. round-bottomed flask are placed 154 g. (1 mole) of acenaphthene (Note 1) and 1.1 l. of glacial acetic acid (Note 2). The flask is fitted with a tantalum or Nichrome wire stirrer1 and a thermometer extending below the surface of the liquid. The solution is stirred and heated to 60, at which point the source of heat is removed and 820 g. of red lead (Note 3) is added in portions of about 50 g., each portion being added as soon as the color due to the previous portion has been discharged. During this operation, which requires 3040 minutes, the temperature is maintained at 6070 (Note 4) by external cooling. The reaction is complete when a portion of the solution gives no test for lead tetraacetate (Note 5). The dark red syrupy solution (which may contain a few suspended particles of red lead and lead dioxide) is poured into 2 l. of water contained in a 4-l. separatory funnel. The acetate is extracted with a 350-ml. portion of ether and then with a 250-ml. portion. The total extract is washed first with 100 ml. of water, then with 300 ml. of saturated sodium chloride solution and is finally dried over 50 g. of anhydrous sodium sulfate. The sodium sulfate is removed by filtration and washed colorless with three 50-ml. portions of dry ether. The combined filtrate and washings are placed in a 500-ml. Claisen flask with an inset side arm, and, after distillation of the solvent, the acetate is distilled under reduced pressure. The acetate distils almost entirely at 166 168/5 mm. (bath temperature 180185, raised to 220 at the end) as a mobile yellow oil. The yield is 170175 g. (8082%) (Note 6). B. Acenaphthenol. The acetate obtained as above is dissolved in 275 ml. of methanol in a 2-l. round-bottomed flask, and a solution of 40 g. (1.2 equiv.) of sodium hydroxide in 400 ml. of water is added (Note 7). This mixture is refluxed for 2 hours (Note 7) and then cooled below 20. The yellow crystalline acenaphthenol is collected on a filter and washed well with about 1.5 l. of water. The crude product is air-dried (138143 g.) and then dissolved in 2 l. of boiling benzene. The solution is treated with 68 g. of decolorizing carbon (Note 8) and filtered through a heated funnel. The orange-red filtrate is concentrated to about 1 l., and the acenaphthenol is allowed to crystallize. After filtering with suction and washing with cold benzene (about 500 ml.) until the wash solvent is colorless, the acenaphthenol is obtained as practically colorless needles, m.p. 144.5145.5 (cor.) (Note 9). It weighs 117121 g. From the filtrate may be obtained an additional quantity of material which on one recrystallization gives only 35 g. of pure acenaphthenol. The total yield amounts to 120126 g. (7074% based on the

acenaphthene).

2. Notes1. The "95% acenaphthene" sold by Reilly Tar and Chemical Corporation melts at 92.593.5 (cor.) and is quite satisfactory for use in this reaction. A recrystallized sample of this acenaphthene (m.p. 93 93.5) or acenaphthene from the Gesellschaft fr Teerverwertung (m.p. 9393.5) gives no better yield of pure acenaphthenol. 2. The glacial acetic acid should be purified by distillation from potassium permanganate. About 3050 g. of potassium permanganate for each 1.5 l. of acetic acid should be used. 3. Mallinckrodt's analytical reagent red lead (assay 8590%) was used. Merck's and Baker's N.F. V red lead are also quite satisfactory. Previously prepared lead tetraacetate is in no way preferable to red lead for this oxidation. 4. If the oxidation is carried out at 50 the yield is unaffected, but several hours are required to complete the addition. At 40, the reaction is very slow and the yield is lowered. 5. A drop of the reaction mixture is placed on a moist piece of starch-iodide paper. The development of a blue color shows the presence of lead tetraacetate. 6. The acenaphthenol acetate contains small amounts of acenaphthene and acenaphthenone but is pure enough for the next step. 7. The dark violet color appearing on addition of the alkali is probably due to the presence of acenaphthenone. Crystalline acenaphthenol begins to separate almost immediately after the alkali has been added. Care must be taken in heating to refluxing because when heated too rapidly the acenaphthenol crystallizes suddenly from solution and the heat evolved may blow part of it out through the condenser. 8. If the charcoal treatment is omitted, the acenaphthenol obtained is light yellow but practically pure. 9. Marquis2 reported the melting point as 148; von Braun and Bayer3 reported it as 146.

3. DiscussionAcenaphthenol has been prepared in poor yield by the oxidation of acenaphthene with lead dioxide;2 and it is among the products obtained by hydrogenation of acenaphthene quinone.3 The above procedure is essentially that described more briefly in the literature.4

References and Notes1. Hershberg, Ind. and Eng. Chem., Anal. Ed., 8, 313 (1936); Org. Syntheses Coll. Vol. 2, 117 (1943). 2. Marquis, Compt. rend., 182, 1227 (1926). 3. von Braun and Bayer, Ber., 59, 920 (1926). 4. Fieser and Cason, J. Am. Chem. Soc., 62, 432 (1940).

Appendix Chemical Abstracts Nomenclature (Collective Index Number); (Registry Number)red lead acetic acid (64-19-7) Benzene (71-43-2) methanol (67-56-1)

ether (60-29-7) sodium hydroxide (1310-73-2) potassium permanganate (7722-64-7) sodium chloride (7647-14-5) sodium sulfate (7757-82-6) carbon (7782-42-5) acenaphthene (83-32-9) acenaphthene quinone (82-86-0) ACENAPHTHENOL-7 1-Acenaphthenol, acenaphthenol (6306-07-6) Acenaphthenol acetate (14966-36-0) acenaphthenone (2235-15-6) lead dioxide lead tetraacetate (546-67-8)Copyright 1921-2005, Organic Syntheses, Inc. All Rights Reserved


-(3-ACENAPHTHOYL)PROPIONIC ACID[Acenaphthenebutyric acid, -oxo]

Submitted by L. F. Fieser Checked by W. W. Hartman and A. Weissberger.

1. ProcedureIn a 3-l. round-bottomed three-necked flask (Note 1), 100 g. (0.65 mole) of pure acenaphthene (Note 2) and 72 g. (0.72 mole) of succinic anhydride are dissolved by warming in 600 ml. of nitrobenzene. The flask is clamped in a large ice bath. Through the central opening is inserted a mercury-sealed mechanical stirrer. A second opening is connected to a gas trap and also carries a thermometer; the third is for the introduction of aluminum chloride. After the mixture has been cooled to about 0, 195 g. (1.46 moles) of aluminum chloride is added in small portions in the course of 1 hour, the temperature being kept below 5. Stirring is continued at 0 for 4 more hours, after which time the mixture is allowed to stand for at least 12 hours so that the ice melts and the clear red solution gradually comes to room temperature. The flask is cooled by immersion in a slush of ice and water, and the addition compound is decomposed by adding gradually 200 g. of ice, 100 ml. of water, and 100 ml. of concentrated hydrochloric acid (this is best done under a hood). The keto acid separates in the form of a stiff, grayish white paste. The solvent is removed by steam distillation, in which operation it is advisable to use a very rapid flow of steam together with an efficient condensing system, such as that illustrated (Fig. 1). The condensing flask shown need be no more than 1 l. in capacity, and the exit tube should be centered at the bottom of this flask so that it can drain the contents completely. Some condensate ordinarily remains in the flask to serve as a vapor seal, a factor which adds greatly to the efficiency of condensation. For purposes of inspection, the flask can be emptied by diverting for a moment the stream of water to one side of the flask. The stoppers which are under pressure should be secured with wire. The distilling flask is heated to prevent too much condensation of steam (Note 3). Fig. 1.

The bulk of the nitrobenzene comes over in about 1.5 hours, and the product then separates as a pasty mass which slowly disintegrates to a powder. During this process the elimination of nitrobenzene is very slow, but the steaming should be continued until only a few small lumps remain (45 hours), although it is not necessary to remove every trace of solvent (Note 4). The mixture is cooled with tap water, the crude acid is filtered and returned to the flask, and 115 g. of sodium carbonate decahydrate is added, together with sufficient water to make the flask a little less than half full. The mixture is heated with shaking over a free flame until most of the solid has dissolved and the frothing has diminished. A few drops of capryl alcohol may be added to dissipate the froth. The dark brown solution is steamdistilled to eliminate the last traces of nitrobenzene (about 30 minutes) and then filtered by suction from a very light residue. One hundred grams of sodium chloride is dissolved in the hot solution (volume, about 1.5 l.), which is then allowed to cool without disturbance. The sodium salt of -(3-acenaphthoyl) propionic acid separates as colorless, fibrous needles, while the isomeric 1-acid largely remains in solution (Note 5). The product is collected on a large Bchner funnel and washed free of the dark mother liquor with half-saturated sodium chloride solution (about 150 ml.), the combined filtrates (A) being set aside. The sodium salt is crystallized once more from boiling water (11.5 l.) (Note 6), using Norit if required, and adding 50 g. of sodium chloride to the hot filtered solution. The mother liquor (B) is again saved. The purified salt is dissolved in 1.2 l. of hot water and the solution is acidified. The free acid separates as a white powder in a very pure condition. The yield of -(3-acenaphthoyl) propionic acid melting at 206208 with decomposition is 133 g. (81%) (Note 7).

2. Notes1. By using a flask suitable for steam distillation, the loss in time and material attending a transfer is avoided. 2. Suitable material is supplied by Reilly Tar and Chemical Corporation, New York, or Gesellschaft fr Teerverwertung, Duisburg-Meiderich, Germany. 3. As compared with the apparatus shown in Fig. 24 of Org. Syntheses Coll. Vol. 1, 479, this arrangement requires a much smaller flask and yet offers unlimited capacity. It also enables the operator to observe more closely the nature of the distillate.

4. If the flask fills up with condensed steam, it should be cooled, the contents filtered, and the product returned to the flask. The process of disintegration can be hastened by breaking up the lumps with a flattened stirring rod. 5. The small amount of isomeric 1-acid may be obtained from the mother liquors, A and B. The first of these on acidification gives a product which is dark and tarry, but which soon solidifies on being cooled and stirred. The material is dissolved in 1 l. of water containing 2530 g. of sodium carbonate decahydrate, and the solution is boiled for 30 minutes with Norit, filtered, cooled, and acidified. The product, which now solidifies at once and is lighter in color, is dried and combined with the material obtained by acidifying the second mother liquor, B (total amount, 23.9 g.). The crude mixture of acids is suspended in 170 ml. of cold methanol, 8.5 ml. of concentrated sulfuric acid is added, and the mixture is heated on the steam bath for about 10 minutes, after which dissolution and esterification are complete. The dark product that crystallizes when the solution cools is largely the 1-ester, which is very much less soluble than the 3-ester. The 1-ester (13.1 g.) is washed free of acid; it crystallizes from ethanol with the use of decolorizing carbon in long needles melting at 126; yield, 9 g. (Note 8). The ester is hydrolyzed by heating with 100 ml. of alcohol and 30 ml. of 25% sodium hydroxide solution until dissolved; the solution is then diluted with water and acidified. The -(1-acenaphthoyl)propionic acid melts at 180 (crystallized from dilute alcohol, 181) and weighs 8.4 g. (5%) (Note 9). 6. If, owing to hydrolysis, the sodium salt fails to dissolve completely, alkali should be added as required. 7. The 3-acid crystallizes well from glacial acetic acid, alcohol, or xylene, but large volumes of solvent are required and there is no change in the melting point. 8. The 3-ester melts at 89. 9. Ordinarily the mother liquors from the preparation and purification of 1-ester will be discarded, but a small additional quantity of the 3-acid may be obtained by concentrating these solutions, adding alkali to hydrolyze the ester, adding water, and acidifying. The precipitated material is purified by crystallizing the sodium salt twice, and from this 8 g. (5%) of the pure 3-acid is obtained. The ratio of 3-acid to 1-acid is dependent on the temperature, lower temperatures favoring the production of 3-acid. At 15 the yield of 3-acid is 87%, and of 1-acid, 5%. At room temperature there is some increase in the proportion of the 1-acid formed, but the product is very dark and difficult to work up, and the total yield is lower even though the aluminum chloride is added in nitrobenzene solution.

3. DiscussionThis procedure is based upon a study1 of the method outlined in the patent literature.2 The procedure is a general one and may be used for the condensation of succinic anhydride with naphthalene and with the mono- and dimethylnaphthalenes, although in no other case are the purification and separation of isomers so easily accomplished. In this particular type of condensation, as well as in certain other types of Friedel-Crafts reactions, nitrobenzene is far superior to the solvents that are more frequently employed. This is partly because of its great solvent power and partly because it forms a molecular compound with aluminum chloride, and so decreases the activity of the catalyst in promoting side reactions.

References and Notes1. Fieser, J. Am. Chem. Soc., 54, 4350 (1932). 2. Fr. pat. 636,065 (Chem. Zentr., 1928, I, 2751); Swiss pat. 131,959 (Chem. Zentr., 1930, I, 1539); U. S. pat. 1,759,111 (Chem. Zentr., 1930, II, 806); Ger. pat. 376,635 [Frdl., 14, 285 (1926)].

Appendix Chemical Abstracts Nomenclature (Collective Index Number); (Registry Number)

alcohol, ethanol (64-17-5) sulfuric acid (7664-93-9) hydrochloric acid (7647-01-0) acetic acid (64-19-7) methanol (67-56-1) sodium hydroxide (1310-73-2) sodium chloride (7647-14-5) Norit (7782-42-5) aluminum chloride (3495-54-3) Nitrobenzene (98-95-3) Naphthalene (91-20-3) sodium carbonate decahydrate (6132-02-1) xylene (106-42-3) Succinic anhydride (108-30-5) capryl alcohol (111-87-5) acenaphthene (83-32-9) -(3-Acenaphthoyl)propionic acid, -(3-acenaphthoyl) propionic acid (16294-60-3) Acenaphthenebutyric acid, -oxo, -(1-acenaphthoyl)propionic acid sodium salt of -(3-acenaphthoyl) propionic acidCopyright 1921-2005, Organic Syntheses, Inc. All Rights Reserved


ACETOACETANILIDE

Submitted by Jonathan W. Williams and John A. Krynitsky. Checked by Nathan L. Drake and Joseph Lann.

1. ProcedureIn a 500-ml. round-bottomed three-necked flask fitted with a reflux condenser, a dropping funnel, and a mercury-sealed stirrer (Note 1) is placed a solution of 46 g. (0.5 mole) of dry aniline in 125 ml. of pure dry benzene. Stirring is started, and a solution of 42 g. (0.5 mole) of ketene dimer (p. 508) in 75 ml. of pure dry benzene is added dropwise over a period of 30 minutes. The reaction mixture is then heated under reflux on the steam bath for 1 hour. After the major portion of the benzene has been removed by distillation from the steam bath, the remainder is removed under reduced pressure. The residue is dissolved in 500 ml. of hot 50% aqueous ethanol from which the acetoacetanilide separates on cooling. The mixture is cooled to 0 before filtration. A second crop of crystals can be obtained by adding 250 ml. of water to the mother liquor and cooling again (Note 2). The total yield of product, m.p. 8283.5, is 65 g. (74%). Further purification by recrystallization from 300 ml. of 50% ethanol yields 55 g. of a product that melts at 8485.

2. Notes1. A seal of rubber tubing lubricated by glycerol is satisfactory. 2. If the second mother liquor is evaporated to about half of its original volume, a small third crop of very impure crystals may be obtained.

3. DiscussionAcetoacetanilide has been prepared by the reaction of aniline with ethyl acetoacetate1,2,3,4,5 or acetoacetyl chloride,6 and by the reaction of ketene dimer with aniline.7,8

References and Notes1. 2. 3. 4. 5. 6. 7. 8. Knorr, Ann., 236, 69 (1886). Roos, Ber., 21, 624 (1888). Knorr and Reuter, Ber., 27, 1169 (1894). Mizuno, J. Pharm. Soc. Japan, 69, 126 (1949). U. S. pat. 2,416,738 [C. A., 41, 3485 (1947)]. Hurd and Kelso, J. Am. Chem. Soc., 62, 1548 (1940). Chick and Wilsmore, J. Chem. Soc., 1908, 946. Boese, Ind. Eng. Chem., 32, 16 (1940).

Appendix Chemical Abstracts Nomenclature (Collective Index Number); (Registry Number)

Ketene dimer ethanol (64-17-5) Benzene (71-43-2) aniline (62-53-3) glycerol (56-81-5) Ethyl acetoacetate (141-97-9) Acetoacetanilide (102-01-2) acetoacetyl chlorideCopyright 1921-2005, Organic Syntheses, Inc. All Rights Reserved


ACETOBROMOGLUCOSE[2,3,4,6-Tetraacetyl--d-glucopyranosyl bromide]

Submitted by C. Ernst Redemann and Carl Niemann. Checked by Lee Irvin Smith, R. T. Arnold, and Iver Lerohl.

1. ProcedureIn a 1-l. round-bottomed flask are placed 66 g. (0.33 mole) of d-glucose monohydrate (Note 1) and 302 g. of 95% acetic anhydride (280 ml., 2.81 moles). To this mixture 3 small drops of concentrated sulfuric acid are added from a medicine dropper (Note 2). The glucose is kept in partial suspension by shaking the flask with a swirling motion; the reaction starts almost immediately. If the temperature of the mixture approaches the boiling point, the flask is momentarily immersed in a pan of cold water. Within 1015 minutes nearly all the glucose will have dissolved and the temperature of the reaction mixture will have risen nearly to 100. The flask is loosely stoppered and is heated on a steam bath for 2 hours. Then about 200 ml. of mixed acetic acid and acetic anhydride is removed by distillation under reduced pressure (Note 3). Sixty-five grams (60 ml., 0.64 mole) of acetic anhydride is added to the warm, viscous, light-yellow syrup; the mixture is warmed slightly and is mixed by imparting a swirling motion to the flask until the solution is homogeneous. The flask is then fitted with a two-holed rubber stopper bearing an inlet tube and an exit tube, the former reaching within 5 mm. of the bottom. Dry hydrogen bromide is passed into the mixture, while it is cooled in an ice bath, until the gain in weight is 140160 g. (Note 4). The flask is then sealed with a rubber stopper and allowed to stand at 5 overnight. The hydrogen bromide, acetic acid, and acetic anhydride are then removed from the straw-yellow solution by distillation under reduced pressure; a water bath whose temperature does not exceed 60 should be used to heat the mixture (Note 5). During the distillation the solution becomes slightly darker. When no further distillate comes over, or when the residue crystallizes, distillation is stopped, 250300 ml. of dry isopropyl ether is added (Note 6), and the flask is warmed carefully on a water bath to hasten solution of the product (Note 7). The hot solution is transferred to a 1-l. Erlenmeyer flask and is cooled rapidly, with cold water, to about 45. The mixture is then allowed to cool slowly to room temperature and is finally placed in a refrigerator at 5 for 2 or more hours. The acetobromoglucose is collected on a Bchner funnel, pressed into a firm cake, and washed with about 50 ml. of dry isopropyl ether. The white crystalline material, after being dried under reduced pressure over calcium (or sodium) hydroxide, weighs 110120 g. (8087%) (Note 8).

2. Notes1. Ordinary commercial glucose monohydrate (Cerelose, Clintose, etc.) was used. 2. If any uncertainty exists about the size of the drops, it is better to add 2 drops at first and then to wait at least 10 minutes before adding the third drop. If too much sulfuric acid is added the reaction may become so vigorous that it cannot be controlled. 3. The lowest pressure attainable with a good aspirator is satisfactory. The acetic acid may be removed rapidly at bath temperatures up to 100. Two hundred milliliters of distillate is collected in about 35 minutes. Complete removal of the acetic acid is not necessary; the only purpose of removing it is to

decrease the amount of hydrogen bromide required. 4. Hydrogen bromide may be generated by dropping liquid bromine into boiling tetrahydronaphthalene, or catalytically from hydrogen and bromine (Org. Syntheses, 15, 35). Free bromine should be removed from the gas by passing it over red phosphorus. The hydrogen bromide may be passed in very rapidly at first, but as the solution becomes more concentrated the rate of introduction of the gas must be decreased. The absorption of 140 g. of hydrogen bromide requires about 2 hours if the solution is well stirred; otherwise a longer time is required. 5. This distillation is best conducted in the following manner: The hydrogen bromide is removed as completely as possible at a bath temperature of 4050 under the pressure attainable with a good aspirator; this requires about 1 hour. The bath temperature is then slowly increased to 5060 over a period of about 30 minutes, during which time considerable acetic acid and acetic anhydride are removed. The receiver is then emptied and the system is connected to a mechanical pump capable of maintaining a pressure of less than 5 mm. By keeping the temperature of the bath at 5560, sufficient acetic acid and anhydride are removed in 3045 minutes. The mechanical pump must be adequately protected; the vapors should be passed through a trap cooled in carbon dioxide-ethanol, then through a 12- to 16-in. tower of flake sodium hydroxide, before they enter the pump. A somewhat higher bath temperature can be used with a good aspirator alone, but this will produce much darkening of the reaction mixture and will give a less desirable product. 6. Isopropyl ether which has been in contact with air for some time will contain peroxides. They should be removed by washing the ether, first with sodium bisulfite solution, then with sodium hydroxide solution, and finally with water. The ether is dried (24 hours over calcium chloride, then 24 hours over phosphorus pentoxide) and distilled. 7. Heating to effect solution should be as brief as possible. The water bath should be at a temperature near the boiling point, and the flask should be immersed for only short periods of time. The flask should be shaken continuously during this process. 8. The product, m.p. 8788, is satisfactory for most purposes. A single recrystallization from isopropyl ether gives a product having a melting point of 8889. The product is best stored in a vacuum desiccator.

3. Discussion-Acetobromoglucose has been prepared by the action of acetyl bromide on anhydrous glucose;1,2,3,4 by the action of hydrogen bromide in acetic acid upon -pentaacetylglucose;5,6,7,8 by the action of hydrogen bromide in acetic anhydride upon anhydrous glucose;9,10 and by the action of hydrogen bromide in acetic anhydride upon starch or maltose.11 This preparation is referenced from: Org. Syn. Coll. Vol. 3, 434 Org. Syn. Coll. Vol. 8, 148 Org. Syn. Coll. Vol. 8, 583

References and Notes1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. Koenigs and Knorr, Ber., 34, 961 (1901). Colley, Ber., 34, 3206 (1901). Moll van Charante, Rec. trav. chim., 21, 43 (1902). Brauns, J. Am. Chem. Soc., 47, 1280 (1925). Fischer, Ber., 49, 584 (1916). Freudenberg, Noe, and Knopf, Ber., 60, 241 (1927). Fischer and Armstrong, Ber., 34, 2892 (1901). Fischer, Ber., 44, 1901 (1911). Dale, J. Am. Chem. Soc., 38, 2187 (1916). Levene and Raymond, J. Biol. Chem., 90, 247 (1931). Bergmann and Beck, Ber., 54, 1576 (1921).

Appendix Chemical Abstracts Nomenclature (Collective Index Number); (Registry Number)red phosphorus calcium (or sodium) hydroxide acetic acid and anhydride -Acetobromoglucose -pentaacetylglucose; ethanol (64-17-5) calcium chloride (10043-52-4) sulfuric acid (7664-93-9) acetic acid (64-19-7) ether (60-29-7) acetic anhydride (108-24-7) hydrogen (1333-74-0) sodium hydroxide (1310-73-2) hydrogen bromide (10035-10-6) bromine (7726-95-6) sodium bisulfite (7631-90-5) carbon dioxide (124-38-9) glucose (492-62-6) tetrahydronaphthalene (119-64-2) Acetobromoglucose (572-09-8) isopropyl ether (108-20-3) glucose monohydrate, d-glucose monohydrate (14431-43-7)

acetyl bromide (506-96-7) maltose phosphorus pentoxide (1314-56-3) 2,3,4,6-Tetraacetyl--d-glucopyranosyl bromideCopyright 1921-2005, Organic Syntheses, Inc. All Rights Reserved


2-ACETOTHIENONE[Ketone, methyl 2-thienyl]

Submitted by Alvin I. Kosak and Howard D. Hartough. Checked by George T. Gmitter, F. Lee Benton, and Charles C. Price.

1. ProcedureIn a 1-l. three-necked flask fitted with a mechanical stirrer, a thermometer, and a reflux condenser are placed 168 g. (2 moles) (Note 1) of thiophene (Note 2) and 107 g. (1 mole) of 95% acetic anhydride (Note 3). The solution is heated to 7075, the source of heat is removed, and 10 g. (6 ml.) of 85% phosphoric acid is added with stirring. After 23 minutes an exothermic reaction occurs, and it is necessary to immerse the flask in a cold water bath to control the reaction. The boiling subsides in a few minutes; heat is again applied, and the mixture is refluxed for a total of 2 hours. The cooled mixture is washed successively with one 250-ml. portion of water and two 100-ml. portions of 5% sodium carbonate and is dried over anhydrous sodium sulfate. The orange-red liquid is distilled through a short fractionating column. After the removal of 7680 g. of unchanged thiophene (b.p. 8384) by distillation at atmospheric pressure the residue is distilled under reduced pressure. The yield of 220 acetothienone, b.p. 8990/10 mm. (m.p. 9.210.5; nD 1.5662), is 93100 g. (7479%).

2. Notes1. Acetic anhydride rather than thiophene may be used in excess, but the unchanged reagent cannot be recovered by the procedure given. With a 3:1 mole ratio of thiophene to anhydride the yield is of the order of 85%. 2. Commercial 99+% thiophene was employed. 3. The use of an equivalent amount of freshly distilled 100% acetic anhydride does not improve the yield.

3. DiscussionIn addition to the methods of preparation given in connection with the procedure1 for the acetylation of thiophene with acetyl chloride in the presence of stannic chloride, 2-acetothienone has been prepared from thiophene and either acetyl chloride or acetic anhydride in the presence of iodine,2 hydriodic acid,2 silica-metal oxides,3 zinc chloride,4 inorganic oxyacids,5,6 and boron trifluoride.7,8,9 It has also been prepared from thiophene and acetic acid in the presence of hydrogen fluoride5 or phosphorus pentoxide.10 The acylation in the presence of phosphorus pentoxide is particularly useful with higher aliphatic acids.10 Procedures using acetic anhydride and stannic chloride or ferric chloride have been described.11

References and Notes1. Org. Syntheses Coll. Vol. 2, 8 (1943). 2. Hartough and Kosak, J. Am. Chem. Soc., 68, 2639 (1946). 3. Hartough, Kosak, and Sardella, J. Am. Chem. Soc., 69, 1014 (1947).

4. 5. 6. 7. 8. 9. 10. 11.

Hartough and Kosak, J. Am. Chem. Soc., 69, 1012 (1947). Hartough and Kosak, J. Am. Chem. Soc., 69, 3093 (1947). U. S. pat. 2,496,786 [C. A., 44, 4930 (1950)]. Heid and Levine, J. Org. Chem., 13, 409 (1948). Hartough and Kosak, J. Am. Chem. Soc., 70, 867 (1948). Levine, Heid, and Farrar, J. Am. Chem. Soc., 71, 1207 (1949). Hartough and Kosak, J. Am. Chem. Soc., 69, 3098 (1947). Farrar and Levine, J. Am. Chem. Soc., 72, 4433 (1950).

Appendix Chemical Abstracts Nomenclature (Collective Index Number); (Registry Number)silica-metal oxides acetic acid (64-19-7) acetic anhydride (108-24-7) acetyl chloride (75-36-5) sodium carbonate (497-19-8) sodium sulfate (7757-82-6) hydrogen fluoride (7664-39-3) iodine (7553-56-2) phosphoric acid (7664-38-2) zinc chloride (7646-85-7) hydriodic acid (10034-85-2) ferric chloride (7705-08-0) Ketone, methyl 2-thienyl (88-15-3) Thiophene (110-02-1) stannic chloride (7646-78-8) boron trifluoride (7637-07-2) phosphorus pentoxide (1314-56-3) 2-Acetothienone (88-15-3)

Copyright 1921-2005, Organic Syntheses, Inc. All Rights Reserved


ACETYLACETONE[Diacetylmethane; 2,4-pentanedione] [I. BORON TRIFLUORIDE METHOD]

Submitted by C. E. Denoon, Jr. Checked by Homer Adkins and Ivan A. Wolff.

1. ProcedureOne hundred and sixteen grams (2 moles) of acetone (Note 1) and 510 g. (5 moles) of reagent grade acetic anhydride are placed in a 2-l. three-necked flask and cooled in an ice-salt bath. One neck of the flask is stoppered; the second neck contains a tube for admitting boron trifluoride; and the third neck contains an outlet tube leading to an alkali trap to catch any unabsorbed boron trifluoride. Commercial grade boron trifluoride (Note 2) is passed through a Kjeldahl bulb, to prevent the reaction mixture from sucking back into the cylinder, and is then bubbled into the reaction mixture at such a rate that 500 g. is absorbed in about 5 hours (2 bubbles per second). The reaction mixture is poured into a solution of 800 g. of hydrated sodium acetate in 1.6 l. of water contained in a 5-l. flask. The mixture is then steamdistilled and the distillate collected in the following portions: 1 l., 500 ml., 500 ml., 400 ml. A solution of reagent grade hydrated copper acetate is made by dissolving 240 g. of the salt in 3 l. of water at about 85 and filtering from any basic acetate. The copper salt of acetylacetone is then precipitated by adding 1.4 l. of the hot copper acetate solution to the first fraction of the acetylacetone, 700 ml. to the second, 500 ml. to the third, and 400 ml. to the fourth fraction. After standing for 3 hours, or better overnight, in a refrigerator the salt is filtered, washed once with water, and sucked dry. The salt is shaken in a separatory funnel with 800 ml. of 20% sulfuric acid and 800 ml. of ether, and the ether layer is removed. The aqueous layer is extracted with 400 ml. and then 200 ml. of ether. The combined extracts are dried with 250 g. of anhydrous sodium sulfate, and the ether is removed by distillation. The residue is distilled through a Widmer column (Note 3) and yields 160170 g. of acetylacetone boiling at 134136 (8085% based on acetone).

2. Notes1. Acetone is preferably dried over anhydrous potassium carbonate or anhydrous calcium sulfate, followed by phosphorus pentoxide if a very dry product is required. Calcium chloride is commonly used (100150 g. per liter), but this is less satisfactory since it combines chemically with acetone.1 For this preparation the checkers used acetone that had been dried over calcium chloride, followed by distillation from phosphorus pentoxide. 2. Boron trifluoride may be purchased in cylinders from Harshaw Chemical Company, Cleveland, Ohio. 3. The Widmer column used contained a spiral 15 cm. in length, 13 mm. in diameter, with 15 turns of the helix.

[II. SODIUM ETHOXIDE METHOD]

Submitted by Homer Adkins and James L. Rainey.

Checked by R. L. Shriner and Neil S. Moon.

1. ProcedureSixty-nine grams (3 gram atoms) of sodium, from which all the oxide coating has been cut away, and 400 ml. of dry xylene (Note 1) are placed in a 1-l. round-bottomed flask and heated until the sodium is melted. The flask is closed with a rubber stopper (Note 2), and the sodium is finely powdered by vigorous shaking. The contents of the flask are transferred to a 3-l. three-necked flask, and the xylene decanted. The sodium is washed with two 100-ml. portions of anhydrous ether (Note 3) by decantation. One liter of anhydrous ether is added, and the flask is placed on a steam bath and fitted with a condenser, Hershberg stirrer (Org. Syntheses, 17, 31), and a 250-ml. dropping funnel. The condenser and dropping funnel are protected by drying tubes containing absorbent cotton (Note 4). One hundred and thirty-eight grams (175 ml., 3 moles) of anhydrous ethanol is placed in the dropping funnel, and the stirrer is started. The alcohol is dropped in over a period of 23 hours with gentle refluxing. The reaction mixture is refluxed with stirring for 6 hours (Note 5) after the addition of the alcohol. The stirrer is stopped, the condenser turned downward, and the ether distilled as completely as possible from the steam bath (Note 6). The condenser is again arranged for refluxing, and 1.2 l. of ethyl acetate(Note 7) is added to the warm sodium ethoxide through the separatory funnel as rapidly as possible. The stirrer is started immediately, and 174 g. (220 ml., 3 moles) of acetone (Note 1, p. 17) is dropped in over a period of 15 20 minutes, refluxing being maintained by heating if necessary. Addition of the acetone must be started as soon as the ethyl acetate has been added. During the addition the solution becomes quite red, and then the mixture turns brown (Note 8). The mixture is refluxed for 1 hour; the stirrer is then stopped and the contents of the flask are allowed to stand at room temperature for 12 hours, during which time crystals of the sodium salt separate. The liquid layer is decanted into a 5-l. flask, and the sodium salt of the diketone is dissolved and washed into the flask with 2.5 l. of ice water. After the salt is dissolved, the ester layer is separated as soon as possible (Note 9). The water layer is extracted twice with 300-ml. portions of ether, and the ether extract is discarded. To the water solution is added ice-cold dilute sulfuric acid (150 g. of concentrated sulfuric acid and 400 g. of cracked ice) until the solution is just acid to litmus. The diketone is extracted from the solution with four 300-ml. portions of ether. The combined ether extracts are dried for 24 hours over 60 g. of anhydrous sodium sulfate in the icebox. The ether solution is decanted into a 2-l. round-bottomed flask, and the sodium sulfate is extracted with 100 ml. of anhydrous ether. This extract is added to the ether solution, and the ether is distilled by means of a steam bath. The residue is transferred to a 500-ml. flask, rinsing with a little ether, and distilled through a Widmer column, the portion boiling between 130 and 139 being collected. This fraction is dried over 5 g. of anhydrous potassium carbonate for 1 hour and, after the carbonate has been removed, is redistilled through the Widmer column. The portion boiling at 134136 is collected; it amounts to 115136 g. (3845% based on acetone).

2. Notes1. The xylene is dried by distillation from sodium. 2. Rubber stoppers should be used throughout, including the drying of reagents, as corks contain some moisture. The stoppers should be boiled in 10% sodium hydroxide solution for 2 hours, thoroughly washed with dilute acetic acid, and dried. 3. Commercial anhydrous ethyl ether and ethanol are satisfactory. If these are unavailable, the ether should be purified as for use in the Grignard reaction and the ethanol as described in Org. Syntheses Coll. Vol. 1, 249 (1941). 4. Absorbent cotton is an excellent drying agent and more convenient for drying tubes than anhydrous calcium chloride.2 It is possible to keep maleic anhydride in a flask, closed only by a plug of absorbent cotton, for 3 weeks without appreciable change in the titration value (F. P. Pingert, private communication). 5. The period of heating varies somewhat with the size of the powdered sodium. Almost all the sodium should be used up before removal of the ether. However, a few small pieces do no harm.

6. The success of the reaction depends upon the quality of the sodium ethoxide used. The product at this point should be white and very finely divided. All moisture must be excluded during its preparation in order to avoid the formation of sodium hydroxide, which markedly lowers the yield. 7. The ethyl acetate is allowed to stand over calcium chloride for 2 days, with occasional shaking. The calcium chloride is removed by filtration, and the ester is allowed to stand over phosphorus pentoxide several hours. It is then distilled directly from the phosphorus pentoxide. 8. After about half of the acetone has been added, the mixture usually sets to a solid mass. The stirrer is turned by hand and the addition of acetone continued. In a few minutes the mass can again be stirred. 9. The ethyl acetate layer is washed with water, sodium bisulfite solution, saturated calcium chloride solution, and again with water. It is further purified as in (Note 6), giving 316400 g. of recovered ester. The amount of recovered ester depends somewhat upon the length of time the two layers are allowed to remain in contact before separating.

3. DiscussionAcetylacetone has been prepared by the reaction of acetyl chloride with aluminum chloride, followed by hydrolysis;3 by the condensation of acetone with ethyl acetate in the presence of sodium,4 sodium amide,5,6 sodium ethoxide,5,7,8 and alkali or alkaline-earth hydrides;9 by the reaction of acetone and acetic anhydride in the presence of boron trifluoride;10 by the pyrolysis of isopropenyl acetate;11,12,13 by the reaction of ethyl acetoacetate and acetic anhydride in the presence of magnesium at 140;11 from methyl or ethyl diacetylacetate by treatment with acids;14 and by the dehydrogenation of 4-pentanol-2one in the presence of Raney nickel.15 This preparation is referenced from: Org. Syn. Coll. Vol. 3, 251 Org. Syn. Coll. Vol. 3, 829

References and Notes1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. Bagster, J. Chem. Soc., 1917, 494. Obermiller and Goertz, Z. physik. Chem., 109, 162 (1924) Combes, Ann. chim. et phys., (6) 12, 207 (1887). Claisen, Ann., 277, 168 (1893). Claisen, Ber., 38, 695 (1905). Adams and Hauser, J. Am. Chem. Soc., 66, 1220 (1944). Claisen and Ehrhardt, Ber., 22, 1010 (1889). Sprague, Beckham, and Adkins, J. Am. Chem. Soc., 56, 2665 (1934). U. S. pat. 2,158,071 [C. A., 33, 6342 (1939)]. Meerwein and Vossen, J. prakt. Chem., 141, 149 (1934). U. S. pat. 2,395,800 [C. A., 40, 3130 (1946)]. Brit. pat. 615,523 [C. A., 43, 7954 (1949)]. Hagemeyer and Hull, Ind. Eng. Chem., 41, 2920 (1949). U. S. pat. 2,395,012 [C. A., 40, 3130 (1946)]. DuBois, Compt. rend., 224, 1734 (1947).

Appendix Chemical Abstracts Nomenclature (Collective Index Number); (Registry Number)copper salt of acetylacetone

condenser Hershberg stirrer methyl or ethyl diacetylacetate ethanol (64-17-5) calcium chloride (10043-52-4) potassium carbonate (584-08-7) sulfuric acid (7664-93-9) acetic acid (64-19-7) ethyl acetate (141-78-6) ether, ethyl ether (60-29-7) acetic anhydride (108-24-7) sodium acetate (127-09-3) sodium hydroxide (1310-73-2) acetyl chloride (75-36-5) magnesium (7439-95-4) carbonate (3812-32-6) sodium sulfate (7757-82-6) sodium bisulfite (7631-90-5) calcium sulfate (7778-18-9) Raney nickel (7440-02-0) acetone (67-64-1) aluminum chloride (3495-54-3) sodium (13966-32-0) sodium ethoxide (141-52-6) copper acetate (142-71-2)

xylene (106-42-3) Ethyl acetoacetate (141-97-9) boron trifluoride (7637-07-2) Acetylacetone, Diacetylmethane, 2,4-pentanedione (123-54-6) maleic anhydride (108-31-6) isopropenyl acetate (108-22-5) 4-pentanol-2-one phosphorus pentoxide (1314-56-3)Copyright 1921-2005, Organic Syntheses, Inc. All Rights Reserved


ACETYLBENZOYL[1,2-Propanedione, 1-phenyl-]

Submitted by W. W. Hartman and L. J. Roll. Checked by A. H. Blatt and Lewis Rothstein.

1. ProcedureIn a 1-l. flask arranged for steam distillation (Note 1), 50 g. (0.31 mole) of isonitrosopropiophenone (Org. Syntheses, 16, 44; Coll. Vol. 2, 363) and 500 g. of 10% sulfuric acid are mixed, and the mixture is distilled with steam until about 2 l. of distillate is collected. During the distillation the flask is heated so that the volume of the reaction mixture is kept roughly constant. The distillation requires about 6 hours, and at the end of this time the liquid in the flask is clear (Note 2). The lower, yellow layer of diketone in the distillate is separated; the water layer is then saturated with salt and extracted with ether, one 80-ml. and two 25-ml. portions being used for each liter of the aqueous solution. The ether extracts are combined with the diketone proper and dried over sodium sulfate. The ether is removed on the steam bath, and the residual material is distilled from a Claisen flask under reduced pressure. Acetylbenzoyl is collected at 114116/20 mm. (Note 3). The yield is 30 32 g. (6670% of the theoretical amount) (Note 4).

2. Notes1. A spray trap should be placed between the flask and the condenser; otherwise some isonitrosoketone will be carried over. The checkers used a "Kjeldahl Connecting Bulb, Cylindrical Type," illustrated as item 2020 in the Pyrex Catalog, LP34, for 1954. 2. On being cooled, the reaction mixture deposits 37 g. of the dioxime of acetylbenzoyl, m.p. 234236 dec.1 3. Other boiling points reported for acetylbenzoyl are 216218, 164165/116 mm., and 102103/12 mm. 4. According to the submitters the reaction can be carried out with about the same percentage yields using five times the amounts of material specified above.

3. DiscussionAcetylbenzoyl has been prepared by dehydrogenation of acetylphenylcarbinol over copper at 350;2 by oxidation of 1-methyl-2-phenylethylene glycol;3 by action of amyl nitrite on isonitrosopropiophenone;4 and by acid hydrolysis of isonitrosopropiophenone5 or of isonitrosobenzyl methyl ketone.6 The last-named reaction is reported to furnish quantitative yields of acetylbenzoyl, but the starting material is not easily accessible. Treatment of propiophenone with amyl nitrite (2 moles) without isolating the isonitroso compound has been mentioned as a method of preparing acetylbenzoyl,4 but the yield of diketone is much better when the isonitroso compound is isolated.7 Acetylbenzoyl also has been prepared by the oxidation of phenyl acetone with selenium dioxide.8

References and Notes

1. 2. 3. 4. 5. 6. 7. 8.

Mller and Pechmann, Ber., 22, 2128 (1889). Mailhe, Bull. soc. chim. France, (4) 15, 326 (1914). Zincke and Zehn, Ber., 43, 855 (1910). Manasse, Ber., 21, 2177 (1888). Pechmann and Mller, Ber., 21, 2119 (1888). Kolb, Ann., 291, 286 (1896); Borsche, Ber., 40, 740 (1907). Coles, Manske, and Johnson, J. Am. Chem. Soc., 51, 2269 (1929). Wegmann and Dahn, Helv. Chim. Acta, 29, 1247 (1946).

Appendix Chemical Abstracts Nomenclature (Collective Index Number); (Registry Number)dioxime of acetylbenzoyl sulfuric acid (7664-93-9) ether (60-29-7) sodium sulfate (7757-82-6) copper (7440-50-8) selenium dioxide (7446-08-4) amyl nitrite (463-04-7) Propiophenone (93-55-0) phenyl acetone (103-79-7) ISONITROSOPROPIOPHENONE 1,2-Propanedione, 1-phenyl- (579-07-7) 1-methyl-2-phenylethylene glycol Acetylbenzoyl (579-07-7) acetylphenylcarbinol isonitrosobenzyl methyl ketoneCopyright 1921-2005, Organic Syntheses, Inc. All Rights Reserved


1-ACETYLCYCLOHEXENE[Ketone, 1-cyclohexenyl methyl]

Submitted by J. H. Saunders1 Checked by E. L. Jenner and R. S. Schreiber.

1. ProcedureIn a 500-ml. round-bottomed flask are placed 40 g. (0.32 mole) of 1-ethynylcyclohexanol (p. 416), 250 ml. of dry benzene, 10 g. of phosphorus pentoxide, and a boiling chip. A reflux condenser is attached to the flask, and the benzene solution is refluxed gently on a steam cone for 2.5 hours. At the end of that time the contents of the flask are cooled and the benzene is decanted from the phosphorus pentoxide, washed once with 100 ml. of 5% sodium bicarbonate solution, and dried over 15 g. of anhydrous sodium sulfate. The benzene is removed by distillation at atmospheric pressure, and the acetylcyclohexene is carefully fractionated at reduced pressure, through a 15-cm. helix-packed column. 20 The yield of material boiling at 8588/22 mm., nD 1.4892, is 22.528 g. (5670%).

3. Discussion1-Acetylcyclohexene has been prepared by treating cyclohexene with acetyl chloride and aluminum chloride,2,3,4,5 by treating 1-ethynylcyclohexanol with oxalic acid6 or 85% aqueous formic acid,5,7,8,9 and by the dehydrohalogenation and hydrolysis of ethylidenecyclohexane nitrosochloride.10 1Acetylcyclohexene and its homologs also have been prepared by the addition of a suitable diene to vinylacetylene in the presence of water and a mercury salt.11

References and Notes1. This investigation was carried out under the sponsorship of the Office of Rubber Reserve, Reconstruction Finance Corporation, in connection with the Government Synthetic Rubber Program. 2. Darzens, Compt. rend., 150, 707 (1910). 3. Christ and Fuson, J. Am. Chem. Soc., 59, 895 (1937). 4. Nightingale, Milberger, and Tomisek, J. Org. Chem., 13, 358 (1948). 5. Hurd and Christ, J. Am. Chem. Soc., 59, 120 (1937). 6. Levina and Vinogradova, J. Applied Chem. U.S.S.R., 9, 1299 (1936) [C. A., 31, 2587 (1937)]. 7. Rupe, Messner, and Kambli, Helv. Chim. Acta, 11, 454 (1928). 8. Fischer and Lwenberg, Ann., 475, 203 (1929). 9. Chanley, J. Am. Chem. Soc., 70, 246 (1948). 10. Wallach, Ann., 360, 46 (1908). 11. U. S. pat. 2,301,515 [C. A., 37, 2015 (1943)].

Appendix

Chemical Abstracts Nomenclature (Collective Index Number); (Registry Number)ethylidenecyclohexane nitrosochloride Benzene (71-43-2) acetyl chloride (75-36-5) sodium bicarbonate (144-55-8) Cyclohexene (110-83-8) sodium sulfate (7757-82-6) formic acid (64-18-6) Oxalic acid (144-62-7) mercury (7439-97-6) aluminum chloride (3495-54-3) 1-Acetylcyclohexene, Ketone, 1-cyclohexenyl methyl, acetylcyclohexene (932-66-1) 1-Ethynylcyclohexanol (78-27-3) vinylacetylene (689-97-4) phosphorus pentoxide (1314-56-3)Copyright 1921-2005, Organic Syntheses, Inc. All Rights Reserved


2-ACETYLFLUORENE[Ketone, 2-fluorenyl methyl]

Submitted by F. E. Ray and George Rieveschl, Jr.. Checked by R. L. Shriner and Arne Langsjoen.

1. ProcedureCaution! Carbon disulfide, used as a solvent in this preparation, is highly inflammable; its vapor may ignite on contact with a hot laboratory steam line. A 1-l. three-necked round-bottomed flask is fitted with a dropping funnel, a reflux condenser attached to a hydrogen chloride absorption trap,1 and a very sturdy mechanical stirrer (Note 1), which may be of the mercury-sealed or rubber-sleeve type. In the flask are placed 350 ml. of dry carbon disulfide and 80 g. (0.48 mole) of fluorene (Note 2). The stirrer is started, and, after the fluorene has dissolved, 128 g. (0.96 mole) of anhydrous aluminum chloride is added in one portion. In the dropping funnel is placed 49.4 g. (0.48 mole) of redistilled acetic anhydride, and about 1 ml. of it is added dropwise to the vigorously stirred dark red reaction mixture. If the reaction does not start immediately it is initiated by warming the reaction flask in a water bath (Note 3). After the reaction has started, the balance of the acetic anhydride is added at such a rate that the carbon disulfide refluxes gently; about 4555 minutes is required. When approximately one-half of the acetic anhydride has been added an addition complex separates as a heavy mass which makes stirring very difficult. However, stirring must be maintained to prevent excessive local reaction at the point of introduction of the acetic anhydride. The mixture is stirred and refluxed on the water bath for an hour after the addition of the acetic anhydride is complete. The dark green mass is collected on a large Bchner funnel and transferred as quickly as possible (Note 4) to a 1-l. beaker in which it is stirred mechanically for 10 minutes with 300 ml. of carbon disulfide (Note 5). The solid is again collected and washed on the filter with two 50-ml. portions of carbon disulfide (Note 6) and with one 100-ml. portion of petroleum ether (b.p. 2835). The resulting granular aluminum chloride complex is decomposed by portionwise addition to a well-stirred mixture of 800 ml. of water and 30 ml. of concentrated hydrochloric acid in a 2-l. beaker under a hood. Each portion is allowed to hydrolyze before the next is added. The hydrolysis mixture should not be cooled. The crude 2-acetylfluorene is collected on a filter and washed three times with 100-ml. portions of water. After drying in an oven at 100 for 3 hours the light-orange ketone weighs 8395 g. (8395%) and melts over the range 113117 (Note 7). This crude product is transferred to a 2-l. round-bottomed flask containing 800 ml. of 95% ethanol and 5 g. of decolorizing carbon. The mixture is refluxed for 1 hour and filtered hot. On cooling the filtrate deposits 7183 g. of light-tan solid melting at 120123. A second recrystallization from 800 ml. of ethanol yields 5563 g. (5563%) of a light-cream-colored powder which melts at 124126 and which is pure enough for most purposes (Note 8).

2. Notes1. The stirrer, which may be of either the half-round or the propeller type, must be of heavy construction and must be driven by one of the more powerful laboratory stirring motors. Agitation must be maintained throughout the reaction period. 2. If technical fluorene (m.p. 103107) from Eastman Kodak Company or the Barrett Company is

used, much difficulty is experienced in the purification of the product. Technical fluorene can be rendered suitable for the preparation by recrystallization from hot 95% ethanol (1 l. for 150 g.). The once-recrystallized material melts at 114115 (lit. 116). 3. It is necessary to make sure that the reaction has started before the addition of more acetic anhydride in order to prevent a violent reaction. 4. Exposure to the air causes the addition product to become sticky and difficult to handle. 5. Unless this operation can be conducted at a point remote from flames, hot plates, and other sources of heat, a flask should be substituted for the open beaker. 6. The carbon disulfide extracts unchanged fluorene and other impurities. Any lumps in the crude material should be crushed during the first washing. The rinsing with petroleum ether removes the last of the carbon disulfide. 7. This crude 2-acetylfluorene is completely soluble in carbon disulfide and thus is free of the insoluble 2,7-diacetylfluorene. It may be used directly for the oxidation to fluorenone-2-carboxylic acid (p. 420). 8. The pure product2 melting at 128129 (cor.) can be obtained in 4245% yield by two more recrystallizations from 400-ml. portions of acetone. Pure 2-acetylfluorene has also been reported3 as melting at 132, but this value has not been checked.

3. Discussion2-Acetylfluorene has been prepared by the reaction of fluorene with acetic anhydride2,4 or with acetyl chloride3,5 in the presence of aluminum chloride in carbon disulfide or in nitrobenzene. When nitrobenzene is employed as the solvent it must be removed by a time-consuming steam distillation, and the use of acetyl chloride as a reagent agent leads to the formation of considerable amounts of 2,7diacetylfluorene. This preparation is referenced from: Org. Syn. Coll. Vol. 3, 420

References and NotesOrg. Syntheses Coll. Vol. 2, 4 (1943). Bachmann and Sheehan, J. Am. Chem. Soc., 62, 2687 (1940). Dziewonski and Schnayder, Bull. intern. acad. polon. sci., 1930A, 529 [C. A., 25, 5416 (1931)]. Ray and Rieveschl, J. Am. Chem. Soc., 65, 836 (1943); Buu-Hoi and Cagniant, Bull. soc. chim. France, 1946, 131. 5. Ardashev, Lomovatskaya, and Kacher, J. Applied Chem. U.S.S.R., 11, 1344 (1938) [C. A., 33, 5844 (1939)]. 1. 2. 3. 4.

Appendix Chemical Abstracts Nomenclature (Collective Index Number); (Registry Number)petroleum ether aluminum chloride complex ethanol (64-17-5) hydrochloric acid (7647-01-0)

acetic anhydride (108-24-7) acetyl chloride (75-36-5) acetone (67-64-1) decolorizing carbon (7782-42-5) aluminum chloride (3495-54-3) Nitrobenzene (98-95-3) carbon disulfide (75-15-0) fluorene (86-73-7) 2-Acetylfluorene, Ketone, 2-fluorenyl methyl (781-73-7) 2,7-diacetylfluorene (39665-89-9) Fluorenone-2-carboxylic acid (784-50-9)Copyright 1921-2005, Organic Syntheses, Inc. All Rights Reserved


9-ACETYLPHENANTHRENE[Ketone, methyl 9-phenanthryl]

Submitted by Joseph E. Callen, Clinton A. Dornfeld, and George H. Coleman1. Checked by Robert E. Carnahan and Homer Adkins.

1. ProcedureA dry 12-l. three-necked flask is equipped with an efficient motor-driven stirrer (Note 1), a nitrogen inlet tube, a large Allihn condenser, and a 1-l. separatory funnel. Both the condenser and the funnel are provided with calcium chloride drying tubes. To the flask is added 146 g. (6 gram atoms) of magnesium turnings (Note 2), and nitrogen gas, first bubbled through concentrated sulfuric acid, is passed in to displace the air. During the reaction the nitrogen atmosphere is maintained. The magnesium is covered with 200 ml. of anhydrous ether, and a few milliliters of a solution of 852 g. (6 moles) of methyl iodide in 1 l. of anhydrous ether is added from the separatory funnel. The reaction starts spontaneously, and then the remainder of the methyl iodide solution is added slowly. When the reaction is complete (Note 3), 4 l. of dry benzene is added, a condenser is arranged for downward distillation, and about 1.2 l. of solvent is distilled (Note 4). The condenser is changed to a reflux position, 609 g. (3 moles) of 9cyanophenanthrene (p. 212) is added quickly through a powder funnel, and the mixture is heated and stirred under reflux for 3 hours. It is then cooled in an ice bath to 0, 3 l. of cold 6 N hydrochloric acid is slowly added (Caution!) from a separatory funnel with stirring, and the mixture is refluxed for 6 to 8 hours (Note 5). After cooling, the layers are separated, the organic layer is washed with dilute sodium bicarbonate solution and placed in a flask equipped for distillation, and the solvent is distilled The oily residue is transferred while still warm to a 1-l. Claisen flask, and the product is distilled under reduced pressure; b.p. 190200/2.5 mm. (168170/1 mm.). The yield is 400430 g. (6165%). The distilled ketone is recrystallized once from ethanol (1.52 l.) to yield 345390 g. (5259%) of 9-acetylphenanthrene of m.p. 7374.

2. Notes1. If a 12-l. three-necked flask is not available, a three-way adapter tube may be used in making the necessary connections. Although a mercury seal may be used, a glycerol-rubber tube seal is adequate.

2. The checkers operated on one-tenth the scale specified. 3. In several runs the Grignard reagent was filtered at this point, but the improvement in yield was not appreciable. 4. The addition of benzene and distillation of part of the solvent raises the reaction temperature. 5. The oily layer of ketimine hydrochloride usually dissolves during 6 hours' refluxing.

3. DiscussionThe method described above is a modification of that of Bachmann and Boatner.2 9Acetylphenanthrene has also been obtained by a Claisen condensation of methyl phenanthrene-9carboxylate with ethyl acetate followed by scission of the resulting phenanthroylacetic ester,3 by the reaction of 9-phenanthrylmagnesium bromide with acetyl chloride,4 and by dehydrogenation of 9acetyl-1,2,3,4-tetrahydrophenanthrene by heating with sulfur.5

References and Notes1. 2. 3. 4. 5. Work done under contract with the Office of Scientific Research and Development. Bachmann and Boatner, J. Am. Chem. Soc., 58, 2098 (1936). Mosettig and van de Kamp, J. Am. Chem. Soc., 55, 3445 (1933). Miller and Bachman, J. Am. Chem. Soc., 57, 768 (1935). Bachmann and Struve, J. Org. Chem., 4, 476 (1939).

Appendix Chemical Abstracts Nomenclature (Collective Index Number); (Registry Number)ethanol (64-17-5) sulfuric acid (7664-93-9) hydrochloric acid (7647-01-0) Benzene (71-43-2) ethyl acetate (141-78-6) ether (60-29-7) acetyl chloride (75-36-5) sodium bicarbonate (144-55-8) magnesium, magnesium turnings (7439-95-4) nitrogen (7727-37-9) sulfur (7704-34-9) Methyl iodide (74-88-4)

9-Acetylphenanthrene, Ketone, methyl 9-phenanthryl (2039-77-2) 9-Cyanophenanthrene (2510-55-6) methyl phenanthrene-9-carboxylate 9-phenanthrylmagnesium bromide 9-acetyl-1,2,3,4-tetrahydrophenanthrene ketimine hydrochlorideCopyright 1921-2005, Organic Syntheses, Inc. All Rights Reserved

Organic Syntheses, CV 3, 28

ACID ANHYDRIDES

Submitted by C. F. H. Allen, C. J. Kibler, D. M. McLachlin, and C. V. Wilson. Checked by Cliff S. Hamilton, Dexter Sharp, and R. Kretzinger.

1. ProcedureA. Heptoic anhydride (enanthic anhydride). In a 250-ml. round-bottomed three-necked flask, equipped with a stirrer, dropping funnel, and thermometer, are placed 15.8 g. (16.1 ml., 0.2 mole) of dry pyridine (Note 1) and 25 ml. of dry benzene (Note 2). Then 14.8 g. (15.5 ml., 0.1 mole) of heptoyl chloride (Note 3) is added rapidly to the stirred solution. The temperature rises only slightly, and a pyridinium complex separates. While stirring is continued, 13.0 g. (14.1 ml., 0.1 mole) of heptoic acid (Note 3) is added from the dropping funnel over a period of 5 minutes. The temperature rises rapidly to 6065 (Note 4), and pyridine hydrochloride is formed. After stirring for 10 minutes, the solid is collected on a chilled Bchner funnel and washed twice with 25-ml. portions of dry benzene (Note 5). The filtrate is concentrated under reduced pressure on the steam bath, and the residue is distilled using a 200-ml. modified Claisen flask.1 The fraction boiling up to 155/12 mm. is discarded; the anhydride is collected at 155162/12 mm. (170173/15 mm.). It amounts to 1920 g. (7883%). B. p-Chlorobenzoic anhydride (benzoic anhydride, p,p'-dichloro-). A mixture of 17.5 g. (0.1 mole) of p-chlorobenzoyl chloride (Note 6) and 50 ml. (0.6 mole) of pyridine in a loosely stoppered 200-ml. flask is warmed on the steam bath for 5 minutes and poured upon 100 g. of cracked ice and 50 ml. of concentrated hydrochloric acid (sp. gr. 1.18). The anhydride separates at once; as soon as the ice has melted sufficiently the mixture is filtered by suction. The solid is washed once with 15 ml. of methanol, then with 15 ml. of dry benzene. The yield is 14.214.6 g. (9698%). Though suitable for most purposes, the crude product can be purified by recrystallization from 250 ml. of dry benzene; the recovery is 90%; it melts at 192193.

2. Notes1. The pyridine was Eastman grade which was dried by long standing over potassium hydroxide for A but used without further drying in B. Adkins' studies on the mechanism of this reaction indicate that the intermediate complex may react with water or with a molar quantity of the acid to form an anhydride.2 2. The benzene is dried by distilling the fist 10% and using the residue directly. 3. The heptoyl chloride, b.p. 173175, and the heptoic acid, b.p. 108109/9 mm., were obtained from the Eastman Kodak Company. 4. When preparing larger amounts, it would probably be better to control the temperature by external cooling as well as by the rate of addition of the acid. 5. Pyridine hydrochloride is hygroscopic; the filtration should be done rapidly, using a Bchner funnel. 6. p-Chlorobenzoyl chloride (m.p. 1415) is readily obtained by refluxing and stirring 156 g. (1.0 mole) of p-chlorobenzoic acid (obtained by the procedure for the o-isomer3) and 200 g. (1.7 moles) of thionyl chloride until solution is complete. The unused thionyl chloride is distilled, under slightly reduced pressure, and the product at 10 to 25 mm.; the yield of p-chlorobenzoyl chloride, b.p. 119 120/22 mm., is 131142 g. (7581%). An additional amount can be secured by working up the fore-run and residue.

3. DiscussionThese procedures are generally applicable to both aliphatic and aromatic compounds. They are reported to fail for furoic anhydride and to give poor results for p-nitrobenzoic anhydride (W. W. Prichard, private communication). They are superior to the common interchange method4 in that they avoid the fractional distillation which is very troublesome in the aliphatic series. They have been used in numerous instances2,5,6,7,8,9,10,11,12 and can be adapted to give mixed anhydrides.13 Benzoic anhydride has been obtained, by closely related procedures, from benzoic acid and benzoyl chloride by heating under reduced pressure14 or in the presence of zinc chloride.15 Benzoic, acetic, and propionic anhydrides have been conveniently prepared by the action of bromine on the sodium salts of the acids in the presence of sulfur.16

References and Notes1. Org. Syntheses Coll. Vol. 1, 130 (1941). 2. Ipatieff and Friedman, J. Am. Chem. Soc., 61, 686 (1939); Adkins and Thompson, J. Am. Chem. Soc., 71, 2242 (1949). 3. Org. Syntheses, 10, 20 (1930); Coll. Vol. 2, 135 (1943). 4. Org. Syntheses Coll. Vol. 1, 91 (1941). 5. Minunni, Gazz. chim. ital., 22, 213 (1892). 6. Einhorn and Holland, Ann., 301, 95 (1898). 7. Wedekind, Ber., 34, 2070 (1901). 8. Losanitsch, Monatsh., 35, 318 (1914). 9. Benary, Reiter, and Soenderop, Ber., 50, 73 (1917). 10. Rule and Paterson, J. Chem. Soc., 125, 2161 (1924). 11. Allen, Wilson, and Ball, Can. J. Research, 9, 434 (1933). 12. Fuson, Corse, and Rabjohn, J. Am. Chem. Soc., 63, 2852 (1941). 13. Knoll and Company, Ger. pat. 117,267 [Frdl., 6, 146 (19001902)]. 14. Dvornikoff, U. S. pat. 1,948,342 [C. A., 28, 2730 (1934)]. 15. Doebner, Ann., 210, 278 (1881). 16. Orshansky and Bograchov, Chemistry & Industry, 1944, 382.

Appendix Chemical Abstracts Nomenclature (Collective Index Number); (Registry Number)Heptoic anhydride (enanthic anhydride heptoyl chloride heptoic acid p-Chlorobenzoic anhydride (benzoic anhydride, p,p'-dichloroBenzoic, acetic, and propionic anhydrides hydrochloric acid (7647-01-0) Benzene (71-43-2)

methanol (67-56-1) thionyl chloride (7719-09-7) bromine (7726-95-6) Benzoic acid (65-85-0) sulfur (7704-34-9) benzoyl chloride (98-88-4) Benzoic anhydride (93-97-0) pyridine (110-86-1) potassium hydroxide (1310-58-3) zinc chloride (7646-85-7) pyridine hydrochloride (628-13-7) furoic anhydride p-chlorobenzoic acid (74-11-3) p-chlorobenzoyl chloride (122-01-0) p-nitrobenzoic anhydrideCopyright 1921-2005, Organic Syntheses, Inc. All Rights Reserved


ACRYLIC ACID[I. PYROLYSIS METHOD]

Submitted by W. P. Ratchford Checked by Arthur C. Cope, William R. Armstrong, and James J. Ryan.

1. ProcedureA 90-cm. length of 28-mm. (outside diameter) Pyrex tubing packed with pieces of Pyrex tubing (Note 1) is mounted vertically in an electric furnace (Note 2) capable of maintaining a temperature of 585595. A 250-ml. long-stemmed separatory funnel is connected to the upper end of the tubing with a stopper (Note 3), and the lower end is connected to a 500-ml. three-necked flask immersed in ice water. The flask, which serves as a receiver, is attached to a 50-cm. water-cooled reflux condenser, which in turn is connected by short lengths of rubber tubing to two traps in series which are immersed in a Dry Icetrichloroethylene mixture. The exit tube of the second trap is vented to a hood. From 0.2 to 0.3 g. of hydroquinone is placed in the receiver, together with a few pieces of Dry Ice which serve to displace air from the entire apparatus. The third neck of the receiver is stoppered. The furnace is heated to 590 (Note 4), and after the air has been displaced 200 g. (216 ml., 2 moles) of ethyl acrylate (Note 5) is placed in the separatory funnel and admitted to the reaction tube at a rate of about 90 drops a minute (Note 3), so that the addition requires about 2 hours. At the end of the addition the contents of the receiver and the small amount of liquid in the traps are combined. The total weight of crude acrylic acid containing some ethyl acrylate is 126136 g. The crude product is placed in a 250-ml. flask containing a capillary inlet tube through which carbon dioxide is admitted. Ten grams of hydroquinone and 15 g. of diphenyl ether are added, and the flask is attached to a suitable fractionating column (Note 6). The product is fractionated carefully (Note 7) at 135 mm. pressure. The pressure is lowered gradually when most of the ethyl acrylate has distilled, and at about 70/90 mm. the receiver is changed. The first fraction (mostly ethyl acrylate) amounts to 9 10 g. The pressure is lowered further to 50 mm., and the acrylic acid is distilled fairly rapidly, without reflux, at 6971/50 mm. The acrylic acid fraction weighs 108116 g. and is 9597% pure according to acidimetric titration. The yield is 6875% based upon 100% acrylic acid content (Note 8) and (Note 9). If the acrylic acid is not to be used at once, it is stabilized by the addition of hydroquinone and is stored in a refrigerator.

2. Notes1. The middle third of the Pyrex tube should be packed with 20-mm. lengths of fire-polished 7-mm. Pyrex tubing. The lower end of the tube is drawn out to a size that permits attachment to the receiver with a rubber stopper. 2. A type FD303 combustion furnace (made and sold by the Hoskins Manufacturing Company, Detroit, Michigan) or any similar furnace is satisfactory. 3. A groove filed in the stopcock of the separatory funnel aids in controlling the rate of addition. If available, a small constant-feed pump may be used to introduce the ester into the pyrolysis tube. The rate of addition of the ester is not critical, but at high rates cracking is incomplete and at low rates the yield is reduced. A stream of nitrogen (100 bubbles per minute) flowing through the tube reduces refluxing and makes the feed rate easier to observe. The nitrogen may be introduced through a tube in the stopper holding the separatory funnel or through a side arm sealed near the upper end of the pyrolysis tube.

4. The temperature is measured by a movable Chromel-Alumel thermocouple located in the furnace by the side of the tube and connected to a potentiometer or millivoltmeter. The thermocouple junction is adjusted so that during the run it is at the hottest point in the furnace. For the Hoskins Company furnace this point is about 9 in. from the top of the furnace. The temperature is controlled manually to 590 5 by means of an autotransformer (Variac) rated at 5 amperes, 110 volts. 5. Commercial ethyl acrylate, containing hydroquinone inhibitor, may be used directly if it is of good quality. 6. The submitter used an insulated column with a 38 by 1.1 cm. section packed with 1/8-in. copper helices made of No. 26 B & S gauge copper wire. He states that a column packed with glass helices is unsatisfactory. The checkers used a 100 by 1.7 cm. Vigreux column. Either type of column should be equipped with a total-condensation partial take-off head. 7. Ethyl acrylate and acrylic acid polymerize easily, and overheating must be avoided in the distillation. The flask is heated in an oil bath which is not permitted to rise above 115. The diphenyl ether that is added serves to expel the acrylic acid at the end of the distillation. 8. The submitter states that the product may be purified by freezing and decanting the supernatant liquid several times. The acrylic acid may be obtained in 97% purity by this method, but it has a faint yellow color. The yield is 5060%. 9. The submitter states that methacrylic acid may be prepared in a similar manner by pyrolyzing ethyl methacrylate. Under the same conditions of temperature and feed rate, the conversion is slightly higher and the yield is about the same.

[II. ACIDOLYSIS METHOD]

Submitted by C. E. Rehberg Checked by Arthur C. Cope and Elbert C. Herrick.

1. ProcedureOne hundred and eighty-four grams (151 ml., 4 moles) of formic acid (Note 1), 1032 g. (1060 ml., 12 moles) of methyl acrylate (Note 2), 30 g. of hydroquinone, and 2 ml. of sulfuric acid are mixed in a 2-l. two-necked round-bottomed flask fitted with a capillary inlet tube. The flask is attached to a 100 by 1.7 cm. Vigreux column (Note 3) and is heated in an oil bath at 8595. The mixture is heated under total reflux until the temperature of the vapor at the still head falls to 32 (after 13 hours). Methyl formate then is distilled slowly at 3235 as long as it is formed (810 hours). A reflux ratio of about 5 to 1 is maintained during the first part of the distillation, which is decreased to total take-off at the end. When no more methyl formate is produced, the excess methyl acrylate is distilled at 3235/140 mm. with the bath temperature at 6065. During the distillation, a slow stream of carbon dioxide is admitted through the capillary inlet. When all the methyl acrylate has been removed, the acrylic acid is distilled at 5356/25 mm. Upon redistillation through the same column (Note 4) acrylic acid of 97% purity (by acidimetric titration) is obtained in a yield of 220230 g. (7478% based upon 100% acrylic acid content), b.p. 5456/25 mm.

2. Notes1. Acetic acid may be used, but it reacts much less rapidly and less completely, and fractionation of the reaction mixture is more difficult. Pure formic acid (98100%) is preferred. 2. Commercial methyl acrylate may be used without purification if it is of good quality. 3. Either a Vigreux column or a column containing an open spiral of copper or Nichrome wire is satisfactory. The column should be jacketed and fitted with a total-condensation variable take-off head. 4. Hydroquinone or another polymerization inhibitor should be added before distillation of acrylic acid or its esters.

3. DiscussionAcrylic acid free of water has been prepared by treating lead acrylate with hydrogen sulfide;1,2 by heating ,-dibromopropionic acid with copper;3 by dry distillation of a mixture of equivalent amounts of sodium acrylate and -chloropropionic acid;4 by pyrolysis of the polymer of -propiolactone;5 by heating -chloropropionic acid with potassium fluoride;6 by heating -acetoxypropionic acid in the presence of hydroquinone;7 by heating lactic acid with metal chlorosulfonates;8 and by the two methods described here.9 It also has been prepared by dehydration of hydracrylic acid in the presence of copper and concentrated acids,10 by acid exchange of acrylates in the presence of polymerization inhibitors,11 and by the reaction of -hydroxypropionitrile with 100% sulfuric acid, followed by addition of water and distillation.12 This preparation is referenced from: Org. Syn. Coll. Vol. 4, 746

References and Notes1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. Caspary and Tollens, Ann., 167, 252 (1873). Wohlk, J. prakt. Chem., (2) 61, 212 (1900). Biilmann, J. prakt. Chem., (2) 61, 491 (1900). Riiber and Schetelig, Z. physik. Chem., 48, 348 (1904). Gresham, Jansen, and Shaver, J. Am. Chem. Soc., 70, 998 (1948); U. S. pat. 2,356,459. Nesmayanov, Pecherskaya, and Uretskaya, Bull. Acad. Sci. U.S.S.R., Classe sci. chim., 1948, 240 [C. A., 42, 4924 (1948)]. U. S. pat. 2,459,677 [C. A., 43, 3026 (1949)]. Brit. pat. 600,653 [C. A., 42, 7320 (1948)]. Ratchford, Rehberg, and Fischer, J. Am. Chem. Soc., 66, 1864 (1944). U. S. pat. 2,469,701 [C. A., 43, 6221 (1949)]. U. S. pat. 2,413,889 [C. A., 41, 2430 (1947)]. U. S. pat. 2,425,694 [C. A., 41, 7410 (1947)].

Appendix Chemical Abstracts Nomenclature (Collective Index Number); (Registry Number)sulfuric acid (7664-93-9) acetic acid (64-19-7) hydroquinone (123-31-9) hydrogen sulfide (7783-06-4) formic acid (64-18-6) nitrogen (7727-37-9) carbon dioxide (124-38-9)

copper (7440-50-8) -hydroxypropionitrile (109-78-4) Acrylic acid (9003-01-4) hydracrylic acid (503-66-2) -Chloropropionic acid (107-94-8) ethyl acrylate (140-88-5) methyl formate (107-31-3) methyl acrylate (96-33-3) lactic acid (50-21-5) diphenyl ether (101-84-8) methacrylic acid (79-41-4) ethyl methacrylate (97-63-2) ,-dibromopropionic acid (600-05-5) sodium acrylate (7446-81-3) -propiolactone (57-57-8) potassium fluoride (7789-23-3) -acetoxypropionic acid lead acrylateCopyright 1921-2005, Organic Syntheses, Inc. All Rights Reserved


-ALANINE

Submitted by Jared H. Ford Checked by Homer Adkins and James M. Caffrey.

1. ProcedureIn a 2-l. three-necked flask equipped with a mechanical stirrer, a thermometer, and a dropping funnel is placed 185 g. (0.55 mole) of technical barium hydroxide octahydrate. The flask is heated on a steam bath in a hood. When the barium hydroxide has dissolved in its water of crystallization, the stirrer is started and 70.1 g. (1.00 mole) of -aminopropionitrile (p. 93) is added dropwise over a period of 40 minutes. The temperature is maintained at 9095 during the addition and for 40 minutes thereafter. Forty grams of asbestos filter aid (Note 1) and 1 l. of hot water are added, and the mixture is saturated with carbon dioxide (Note 2) while the temperature is held at 8590. The mixture is filtered with suction, the precipitate is returned to the flask with 500 ml. of hot water, and the mixture is heated and stirred for 20 minutes. After the barium carbonate has been filtered the washing procedure is again repeated with a second 500 ml. of hot water. The combined filtrates and washings are concentrated under reduced pressure on the steam bath (Note 3) until solid material separates. To the residue are added 200 ml. of hot water and 0.5 g. of decolorizing carbon (Note 4). The resulting solution is warmed on the steam bath for a few minutes and then filtered into a weighed 500-ml. Erlenmeyer flask. The flask is heated on a steam bath, and a jet of clean compressed air is directed at the surface of the solution. When the total weight of the solution is 130 g., it is cooled to 1520 and diluted slowly with 400 ml. of methanol. After the solution has stood for several hours in the refrigerator, the product is filtered with suction and washed with two 100-ml. portions of methanol. The yield of -alanine melting at 197198 (dec.) is 7580 g. (8590%).

2. Notes1. Standard Super-Cel (Johns-Manville, Inc.) was used. 2. Either carbon dioxide gas or Dry Ice may be used, and the saturation may be completed in 1520 minutes by either method. The pH of the saturated solution is about 89 when tested with a universal indicator paper, such as Alkacid or Hydrion. 3. The submitter used a special apparatus suitable for the rapid evaporation of water under reduced pressure. The checkers used standard flasks. 4. The solution is nearly colorless at this point, but the carbon aids in the removal of finely divided insoluble material.

3. Discussion-Alanine has been prepared by the catalytic reduction of cyanoacetic acid,1 esters,2 or salts;3 by heating acrylonitrile,4 -aminopropionitrile,5 bis-(-cyanoethyl) amine,6 -hydroxypropionitrile,7 alkoxypropionitriles,8 bis-(-cyanoethyl) ether,9 or bis-(-cyanoethyl) sulfide9 with aqueous ammonia at 150225; by the hydrolysis of -aminopropionitrile with concentrated hydrochloric acid and subsequent removal of the acid with anion-exchange resins;10 by hydrolysis of phthalimidopropionitrile prepared from phthalimide and acrylonitrile;11 from ,'-iminodipropionic acid, ,'-iminopropionitrile, or diethyl-,'-iminopropionate through preliminary conversion with phthalic

anhydride at 200 to the corresponding phthalimide and subsequent hydrolysis.12 The method as described above has been published.13 Additional references to methods of preparation are given in connection with a procedure for making -alanine from succinimide through the action of potassium hypobromite.14,15

References and Notes1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. Swiss pat. 226,014 [C. A., 43, 2225 (1949)]. U. S. pat. 2,365,295 [C. A., 39, 4626 (1945)]. U. S. pat. 2,367,436 [C. A., 39, 3012 (1945)]. U. S. pat. 2,335,997 [C. A., 38, 2972 (1944)]. U. S. pat. 2,336,067 [C. A., 38, 2971 (1944)]. U. S. pat. 2,334,163 [C. A., 38, 2667 (1944)]. U. S. pat. 2,364,538 [C. A., 39, 3556 (1945)]. U. S. pat. 2,335,605 [C. A., 38, 2970 (1944)]. U. S. pat. 2,335,653 [C. A., 38, 2970 (1944)]. Buc, Ford, and Wise, J. Am. Chem. Soc., 67, 92 (1945). Galat, J. Am. Chem. Soc., 67, 1414 (1945). Chodroff, Kapp, and Beckmann, J. Am. Chem. Soc., 69, 256 (1947). Ford, J. Am. Chem. Soc., 67, 876 (1945). Org. Syntheses Coll. Vol. 2, 20 (1943). Parshin, Zhur. Obshchei Khim., 20, 1826 (1950) [C. A., 45, 2407 (1951)].

Appendix Chemical Abstracts Nomenclature (Collective Index Number); (Registry Number),'-iminopropionitrile diethyl-,'-iminopropionate hydrochloric acid (7647-01-0) ammonia (7664-41-7) methanol (67-56-1) carbon dioxide (124-38-9) phthalic anhydride (85-44-9) carbon (7782-42-5) Phthalimide (85-41-6) -hydroxypropionitrile (109-78-4) cyanoacetic acid (372-09-8) barium hydroxide (17194-00-2)

barium carbonate (513-77-9) barium hydroxide octahydrate (12230-71-6) -Alanine (107-95-9) Succinimide (123-56-8) -Aminopropionitrile (151-18-8) acrylonitrile (107-13-1) bis-(-cyanoethyl) amine (111-94-4) bis-(-cyanoethyl) ether (1656-48-0) bis-(-cyanoethyl) sulfide (111-97-7) -phthalimidopropionitrile potassium hypobromite ,'-iminodipropionic acidCopyright 1921-2005, Organic Syntheses, Inc. All Rights Reserved


ALLOXAN MONOHYDRATE[Alloxan] [I. METHOD A]

Submitted by W. W. Hartman and O. E. Sheppard. Checked by C. S. Marvel and B. H. Wojcik.

1. ProcedureIn a 500-ml. flask (Note 1), fitted with a mechanical stirrer, are placed 36 ml. of water and 25 g. (0.078 mole) of finely crystalline alloxantin dihydrate (p. 42). The flask and contents are heated on a steam bath to 50, and 3.6 ml. of fuming nitric acid (sp. gr. 1.62) is added in a fine stream while vigorous stirring is maintained and the temperature is not allowed to rise above 60 (Note 2). After all the fuming nitric acid has been added, the temperature is brought to 55 and the stirrer is stopped. In a few minutes a vigorous reaction begins, and large quantities of oxides of nitrogen are evolved. The stirrer is again started, and, if the reaction becomes too violent, the mixture is cooled somewhat; otherwise, the reaction is allowed to take its course. The reaction is complete when a current of air, introduced into the flask above the mixture, does not produce much color due to formation of nitrogen tetroxide (Note 3). The mixture is then heated to 6065 for 1015 minutes, whereupon practically all the solid dissolves. The reaction mixture is poured into a glass (Pyrex) tray and cooled overnight at 0 or below. The large triclinic, colorless crystals of alloxan tetrahydrate are broken up, filtered with suction, washed with ice water, and pressed as dry as possible. The crystals are then added to 2526 ml. of hot water (Note 4), and the mixture is shaken until solution is complete. The solution is filtered immediately, and the filtrate is cooled overnight in a tray at 0. The crystals are broken up, filtered, washed with ice water, and pressed as dry as possible. These moist crystals of the tetrahydrate, which weigh 2224 g., are dried to constant weight in a glass tray over concentrated sulfuric acid. The resulting product is a fine white powder (Note 5) which weighs 16 g. The mother liquor from the recrystallization is placed in a 250-ml. flask and is concentrated to a volume of 810 ml. under reduced pressure at not over 3040 (Note 6). The concentrate, when cooled overnight at 0, deposits a solid which is filtered, recrystallized from its own weight of boiling water, and dried over sulfuric acid. This solid weighs about 2 g. The mother liquors from the two crystallizations are combined with the original mother liquor from the oxidation, and the whole is evaporated to dryness under diminished pressure at not above 3040. This solid residue is somewhat yellow and possesses a strong odor of nitric acid. It is kept on a tray for several days until the odor of nitric acid disappears, and then it is dissolved in its own weight (23 g.) of boiling water, and the solution is cooled for several days below 0 (Note 7). The solid is removed, recrystallized from water, and dried over sulfuric acid (Note 8). This crop weighs about 0.5 g. The total yield of alloxan monohydrate is 1819 g. (7276%) (Note 9).

2. Notes1. The large flask is necessary because the mixture foams greatly during the reaction. 2. Very little reaction occurs during the addition of the nitric acid, and consequently there is very little rise in temperature. The acid is added during a few minutes. 3. The reaction is complete in about 30 minutes.

4. The water must not be boiled during the addition of the crystals or afterwards as this will cause decomposition of the alloxan to carbon dioxide, parabanic acid, and alloxantin. 5. The tetrahydrate effloresces readily, gradually loses part of its water, and becomes moist when allowed to stand at room temperature. For this reason it is not suitable for storage. The monohydrate results when the material is dried over sulfuric acid. Drying in an oven is likely to result in local overheating and decomposition, which starts slightly above 100; it is also likely to result in reddening if even a trace of ammonia or amines is present in the air. 6. A higher temperature is likely to cause oxidation and to result in a violent reaction which may become explosive as the nitric acid becomes concentrated. 7. Alloxan tetrahydrate crystallizes from solution much more slowly when it is nearly free of nitric acid and when other soluble substances are present; it is, however, less soluble in nitric acid solution than in water. 8. A little alloxan still remains in solution. The mother liquor still slowly colors the skin red and on standing deposits alloxantin. The alloxantin can be removed and used in another oxidation. About 0.3 0.5 g. of it may deposit after the filtrate has stood for some time. 9. The submitters obtained the same yields (per cent) when approximately 65 times these amounts of materials were used. Thus, carrying out the oxidation of 1610 g. (5 moles) of alloxantin dihydrate in a 22-l. flask, the submitters obtained 1085 g. of the first crop, 160 g. of the second, and 28 g. of the third, a total of 1273 g.

[II. METHOD B]

Submitted by John H. Speer and Thomas C. Dabovich. Checked by W. E. Bachmann and R. O. Edgerton.

1. ProcedureA. Benzalbarbituric acid. A mixture of 128 g. (1 mole) of barbituric acid and 1250 ml. of water in a 2-l. three-necked round-bottomed flask equipped with an efficient stirrer and a reflux condenser is heated on a steam bath to effect solution (Note 1). When the acid has dissolved, 115 g. (110 ml., 1.08 moles) of benzaldehyde is added while heating and stirring are continued. The solution rapidly fills with the insoluble benzalbarbituric acid. The mixture is heated for 1 hour on the steam bath to complete the reaction, and then is filtered by suction (Note 2). The filter cake is washed with several portions of hot water and dried at 100. The yield is 190205 g. (8895%) of product possessing a very pale yellow color. The substance melts at 254256 and needs no further purification. B. Alloxan monohydrate. A mixture of 730 ml. of acetic acid, 95 ml. of water, and 162 g. (1.62 moles) of chromium trioxide (

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Organic Syntheses Collective Volume 3