Organic Syntheses, Coll. Vol. 6, p.293 (1988); Vol. 59, p.42 (1979).

Organic Syntheses, Coll. Vol. 1, p.327 (1941); Vol. 5, p.71 (1925).ISATINSubmitted by C. S. Marvel and G. S. Hiers.Checked by J. B. Conant1. Procedure(A) Isonitrosoacetanilide.—In a 5-l. round-bottomed flask are placed 90 g. (0.54 mole) of chloral hydrate and 1200 cc. of water. To this solution are then added, in order: 1300 g. of crystallized sodium sulfate(Note 1); a solution of 46.5 g. (0.5 mole) of aniline(Note 2) in 300 cc. of water to which 51.2 g.(43 cc., 0.52 mole) of concentrated hydrochloric acid (sp. gr. 1.19) has been added to dissolve the amine (Note 3); and, finally, a solution of 110 g. (1.58 moles) of hydroxylamine hydrochloride(Note 4) in 500 cc. of water. The flask is heated over a wire gauze by a Meker burner so that vigorous boiling begins in about forty to forty-five minutes. After one to two minutes (Note 5) of vigorous boiling the reaction is complete. During the heating period, some crystals of isonitrosoacetanilide separate. On cooling the solution in running water the remainder crystallizes, is filtered with suction, and air-dried. The yield is 65–75 g. (80–91 per cent of the theoretical amount) of a product melting at 175°.(B) Isatin.—Six hundred grams (326 cc.) of concentrated sulfuric acid (sp. gr. 1.84) is warmed to 50° in a 1-l. round-bottomed flask fitted with an efficient mechanical stirrer, and, to this, 75 g. (0.46 mole) of dry (Note 6)isonitrosoacetanilide is added at such a rate as to keep the temperature between 60° and 70° but not higher (Note 7). External cooling should be applied at this stage so that the reaction can be carried out more rapidly. After the addition of the isonitroso compound is finished, the solution is heated to 80° and kept at this temperature for about ten minutes to complete the reaction. Then the reaction mixture is cooled to room temperature and poured upon ten to twelve times its volume of cracked ice. After standing for about one-half hour, the isatin is filtered with suction, washed several times with cold water to remove the sulfuric acid, and then dried in the air. The yield of crude isatin, which melts at 189–192°, is 47–52 g. (71–78 per cent of the theoretical amount). This product is pure enough for many purposes (Note 8).For purification, 200 g. of the crude product is suspended in 1 l. of hot water and treated with a solution of 88 g. of sodium hydroxide in 200 cc. of water. The solution is stirred mechanically and the isatin passes into solution. Dilute hydrochloric acid is then added, with stirring, until a slight precipitate appears. This requires about 290–300 cc. of an acid made by diluting one volume of concentrated hydrochloric acid (sp. gr. 1.19) with two volumes of water (Note 9). The mixture is then filtered at once, the precipitate is rejected, and the filtrate is made acid to Congo red paper with hydrochloric acid. The solution is then cooled rapidly, and the isatin which separates is filtered with suction and dried in the air. The pure product thus obtained weighs 150–170 g. (Note 10) and (Note 11) and melts at 197–200° (corr.).Isatin may also be crystallized from three times its weight of glacial acetic acid. In this case it isobtained in large brown-red crystals which melt at 196–197°.2. Notes1. Several runs were made in which the amounts of water and sodium sulfate were varied over a considerable range, and this concentration was found to give the best yield of product of good quality. The sodium sulfate seems to have more than a salting-out effect. If a saturated solution of sodium chloride is used no product is obtained.2. Redistilled aniline boiling over a 2° range was used in these experiments. The ordinary "pure" grade gives slightly lower yields.3. If the aniline is not in solution, a considerable quantity of tarry material is formed during the heating period. No tar is formed when the method described is used.4. The hydroxylamine hydrochloride used was the crude material prepared as described on p. 318. Preliminary experiments showed that this reagent must be present in considerable excess. Equally good results were obtained by using a solution of crude hydroxylamine sulfate which also contained sodium sulfate and ammonium sulfate with a little excess sulfuric acid. The hydroxylamine content was determined in this solution by titration with potassium permanganate solution. When this crude solution is used, the addition of sodium sulfate is not always necessary.5. Longer heating of the reaction mixture gives a lower yield of dark-colored product.6. If too much moisture is left in the isonitrosoacetanilide it is not easy to control the reaction with sulfuric acid.7. The reaction does not start below 45–50° but becomes too violent above 75–80°. If the temperature becomes too high, the entire run is lost by charring. Stirring is needed to prevent local overheating.8. In some smaller preparations when the sulfuric acid solution was poured on ice a yellow compound precipitated, which was shown to be the oxime of isatin. It has also been isolated from the acid mother liquors from which the isatin has separated. The oxime probably owes its formation to the hydrolysis of some unaltered isonitrosoacetanilide (J. P. Wibaut,1 private communication).9. The correct amount of acid that must be added to precipitate the impurities but not the isatin will vary with different samples of crude isatin. If too much acid is added, some isatin comes down with the impurities. This may be saved and added to a subsequent run.10. The yield of isatin is lower than for some of its derivatives. The explanation given in the literature is that some sulfonation occurs during the treatment with sulfuric acid, with corresponding loss of product.11. This method can be applied successfully to other isatin derivatives. Thus, under the same conditions, 54 g. of p-toluidine gives 75–77 g. (83–86 per cent of the theoretical amount) of isonitrosoaceto-p-toluidine melting at 162°. Eighty grams of this isonitroso compound treated as described under isonitrosoacetanilide gives 65–68 g. (90–94 per cent of the theoretical amount) of crude 5-methyl isatin melting at 179–183°. This is purified as described under isatin by solution in sodium hydroxide and partial neutralization to throw out the impurities or by recrystallization from three parts of glacial acetic acid. The purified 5-methyl isatin melts at 187°.3. DiscussionIsatin can be prepared by the oxidation of indigo;2 and the condensation of aniline, chloral hydrate, and hydroxylamine salts, followed by the action of sulfuric acid.3 The latter method by Sandmeyer3 seemed most promising and has been studied in detail. The procedure described differs from it in the use of hydroxylamine hydrochloride itself instead of a crude solution of hydroxylamine sulfate, and in the use of sodium sulfate to salt out the isonitroso compound.This preparation is referenced from:z Org. Syn. Coll. Vol. 5, 635References and Notes1.Wibaut and Geerling, Rec. trav. chim. 50, 41 (1931).2.Erdmann, J. prakt. Chem. 24, 11 (1841); Laurent, ibid. 25, 434 (1842); Gericke, ibid. 95, 177(1865); Knop, ibid. 97, 86 (1866); Knape, ibid. (2) 43, 211 (1891); Hofmann, Ann. 53, 10 (1845); Sommaruga, Ann. 190, 369 (1878); Gericke, Jahresber. 580 (1865); Forrer, Ber. 17, 976 (1884); Diez and Co., Ger. pat. 229,815 [Frdl. 10, 353 (1910–12)]; Rabinovich and Dzirkal, Khim. Farm. Prom. 1933, 190 [C. A. 28, 475 (1934)]; Henesy, J. Soc. Dyers Colourists, 53, 345, 347 (1937).3.Sandmeyer, Helvetica Chim. Acta 2, 237, 239 (1919); Geigy, Brit. pat. 128,122 [C. A. 13, 2375(1919)].AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)isonitroso compoundindigohydroxylamine saltssulfuric acid (7664-93-9)hydrochloric acid (7647-01-0)acetic acid (64-19-7)aniline (62-53-3)sodium hydroxide (1310-73-2)potassium permanganate (7722-64-7)sodium chloride (7647-14-5)sodium sulfate (7757-82-6)Hydroxylamine hydrochloride (5470-11-1)ammonium sulfate (7783-20-2)hydroxylamine (7803-49-8)Isatin (91-56-5)chloral hydrate (302-17-0)isonitrosoacetanilide (1769-41-1)hydroxylamine sulfate (10046-00-1)5-methyl isatin(608-05-9)p-toluidine (106-49-0)isonitrosoaceto-p-toluidine Copyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。

查⽿酮的制备Organic Syntheses, Coll. Vol. 1, p.78 (1941); Vol. 2, p.1 (1922).BENZALACETOPHENONE[Chalcone]Submitted by E. P. Kohler and H. M. Chadwell.Checked by H. T. Clarke and R. P. Leavitt.1. ProcedureA solution of 218 g. (5.5 moles) of sodium hydroxide in 1960 g. of water and 1000 g. (1225 cc.) of95 per cent alcohol are introduced into a 5.5-l. bottle which is loosely covered with a perforated disk of cardboard, supplied with an effective stirrer, and supported in a larger vessel so as to permit cooling with cracked ice. Into the alkaline solution, 520 g. (4.3 moles) of pure acetophenone(Note 1) is poured, the bottle is rapidly surrounded with cracked ice, and the stirrer started; 460 g. (4.3 moles) of u. s. p. benzaldehyde(Note 2) is then added at once. The temperature of the mixture should not be below 15° and it should not be allowed to rise above 30° during the reaction (Note 3). If it tends to do so, the stirring is not sufficiently vigorous.It is advantageous, though not essential, to inoculate the mixture with a little powdered benzalacetophenone after stirring for one-half hour. After two to three hours, the mixture becomes so thick that the stirring is no longer effective. The stirrer is then removed and the mixture left to itself in an ice box for about ten hours. The mixture now is a thick paste composed of small shot-like grains suspended in an almost colorless liquid. It is cooled in a freezing mixture and then either centrifuged or filtered on a large Büchner funnel, washed with water until the washings are neutral to litmus, and finally washed with 200 cc. of 95 per cent alcohol, which has previously been cooled to 0°. After thorough drying in the air, the crude product weighs about 880 g. (97 per cent of the theoretical amount) and melts at 50–54°. It is sufficiently pure for most purposes but tenaciously holds traces of water. It is most readily purified by recrystallization from four to four and one-half times its weight of 95 per cent alcohol(Note 4). Eight hundred and eighty grams of crude product give 770 g. (85 per cent of the theoretical amount) of light yellow material (m. p. 55–57°) and 40–50 g. that require recrystallization.2. Notes1. The acetophenone should be as pure as possible (m. p. 20°). Commercial acetophenone contains variable quantities of impurities which reduce the yield. By distilling commercial acetophenone with the help of a good still-head (preferably under diminished pressure) and using only the fraction which boils at 201–202° (76–77° /10 mm.) greater quantities of benzalacetophenone can be obtained than by using the entire sample.2. Commercial benzaldehyde can be used in place of the purer product, but the amount used must be increased to make up for the impurities which are present.3. If the temperature is too low, or the stirring too slow, the product separates as an oil, which later solidifies in large lumps. If the temperature is allowed to rise above 30°, secondary reactions diminish both the yield and the purity of the product. The most favorable temperature is 25°.4. In recrystallizing benzalacetophenone, the alcohol should be saturated at 50°. If the solution is saturated above this temperature, the benzalacetophenone tends to separate as an oil. The solution should be allowed to cool gradually, and should finally be chilled in a freezing mixture.3. DiscussionBenzalacetophenone can be prepared from benzaldehyde and acetophenone, by the use of either acid1 or alkaline condensing agents. The alkaline agents are superior and those generally used are a 30 per cent solution of sodium methoxide at low temperatures2 and alcoholic sodium hydroxide.3 Preliminary experiments showed that condensation with sodium methoxide requires a long time and gives a product which is difficult to handle in large quantities.This preparation is referenced from:z Org. Syn. Coll. Vol. 1, 101z Org. Syn. Coll. Vol. 1, 205z Org. Syn. Coll. Vol. 2, 167z Org. Syn. Coll. Vol. 2, 236z Org. Syn. Coll. Vol. 2, 498z Org. Syn. Coll. Vol. 5, 1135References and Notes1.Claisen and Claparède, Ber. 14, 2463 (1881); Straus and Grindel, Ann. 439, 276 (1924); Breslow and Hauser, J. Am. Chem. Soc. 62, 2385 (1940).2.Claisen, Ber. 20, 657 (1887).3.Kostanecki and Rossbach, Ber. 29, 1492 (1896); Schlenck and Bergmann, Ann. 463, 234 (1928). AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)alcohol (64-17-5)sodium hydroxide (1310-73-2)Benzalacetophenone,Chalcone (94-41-7)benzaldehyde (100-52-7)Acetophenone (98-86-2)sodium methoxide (124-41-4)Copyright ? 1921-2005, Organic Syntheses, Inc. All Rights Reserved。

Organic Syntheses, Coll. Vol. 5, p.30 (1973); Vol. 40, p.5 (1960).2-AMINOFLUORENE[2-Flurenylamine]Submitted by P. M. G. Bavin1Checked by John C. Sheehan and Roger E. Chandler..1. ProcedureIn a 2-l. three-necked round-bottomed flask, equipped with a mechanical stirrer (Note 1), reflux condenser, and dropping funnel, are placed 30 g. of pure 2-nitrofluorene, m.p. 157° [Org. Syntheses, Coll. Vol. 2, 447 (1943)], and 250 ml. of 95% ethanol. After warming to 50° on a steam bath, 0.1 g. of palladized charcoal catalyst (previously moistened with alcohol) is added (Note 2) and the stirrer is started. About 15 ml. of hydrazine hydrate is added from the dropping funnel during 30 minutes (Note 3). At this point an additional 0.1 g. of catalyst (previously moistened with alcohol) is added and the mixture is heated until the alcohol refluxes gently. After 1 hour the nitrofluorene has dissolved completely and the supernatant liquor is almost colorless.The catalyst is removed by filtration with gentle suction through a thin layer of Celite (Note 4). The flask is rinsed with 30 ml. of hot alcohol which is then used to wash the catalyst and Celite. The combined filtrates are concentrated under reduced pressure to about 50 ml. (Note 5) and then heated to boiling at atmospheric pressure. When 250 ml. of hot water is added slowly, 2-aminofluorene is precipitated as a colorless, crystalline powder. After cooling in an ice bath, the 2-aminofluorene is collected, washed with water, and dried in the dark in a vacuum desiccator. The product melts at 127.8–128.8° (Note 6) and amounts to 24–25 g. (93–96%).2. Notes1. If the stirring is omitted, the nitrofluorene takes longer to dissolve.2. A suitable catalyst is 10% palladium-on-charcoal, such as is supplied by Baker and Company, Inc., 113 Astor Street, Newark 5, New Jersey.3. The reaction is exothermic, and too rapid addition of the hydrazine may cause the mixture to foam out of the condenser.4. Caution! The catalyst is often pyrophoric and should be kept moistened with alcohol. Celite is a diatomaceous earth filter aid.5. A rotary evaporator is very convenient for the concentration since some of the amine invariably crystallizes toward the end.6. The melting point is that reported in Organic Syntheses, Coll. Vol. 2, 448 (1943), for a recrystallized sample.3. DiscussionThe preparation of 2-aminofluorene reported previously in Organic Syntheses[Coll. Vol. 2, 448 (1943)] we based on the method of Diels.2The present procedure illustrates a general method for the reduction of aromatic nitro compounds to aromatic amines using hydrazine and a hydrogenation catalyst such as palladium, platinum, nickel, iron, or rethenium. The literature on this procedure up to 1963 has been reviewed.3 In many instances the catalytic hydrazine reductions give yields of amine equal to or better than those obtained by directcatalytic hydrogenation or other reduction methods. Both the apparatus and the procedure are simple. Under appropriate conditions the method may be used for the dehalogenation of aliphatic and aromatic halides,3 a reaction for which palladium appears to be a specific catalyst. The method has also been used for the reduction of azobenzene and azoxybenzene to hydrazobenzene (80–90%),4 as well as for the synthesis of steroid aziridines by reduction of mesylate esters by vicinal azido alcohols (using Raney nickel).5References and Notes1.National Research Council of Canada Post-doctorate Fellow, 1954-56, at the University ofOttawa, Ottawa, Ontario.2.O. Diels, Ber., 34, 1758 (1901).3. A. Furst, R. C. Berlo, and S. Hooton, Chem. Rev., 65, 51 (1965).4.P. M. G. Bavin, Can. J. Chem., 36, 238 (1958).5.K. Ponsold, Ber., 97, 3524 (1964).AppendixChemical Abstracts Nomenclature (Collective Index Number);(Registry Number)2-Flurenylaminepalladized charcoal catalystpalladium-on-charcoalethanol (64-17-5)iron (7439-89-6)platinum (7440-06-4)nickel,Raney nickel (7440-02-0)palladium (7440-05-3)hydrazine hydrate (7803-57-8)hydrazine (302-01-2)Azoxybenzene (495-48-7)Azobenzene (103-33-3)2-Nitrofluorene (607-57-8)2-Aminofluorene(153-78-6)Nitrofluoreneretheniumhydrazobenzene (122-66-7) Copyright © 1921-2005, Organic Syntheses, Inc. All Rights Reserved。

TBSO OH NMe2
Organic Syntheses,Coll.Vol.10,p.442;Vol.78,p.160
Work up: The reaction mixture is stirred for 15 min, diluted with ether(100 mL), and quenched by dropwise addition of water (9 mL). The resulting gray suspension is allowed to reach RT, and the mixture is stirred vigorously for an additional 60 min.The mixture is transferred to a 1.0-L Erlenmeyer flask and diluted with ether(350 mL).
NaBH4还原
NaBH4 H3CO2C N CO2CH3 HO N OH
Liebigs Ann.lRecueil 1997,707-720. 此法操作较为简单，安全．由于NaBH4的还原性不够强，因此此类反应一 般需要回流过夜．而且，反应初始阶段不要去加热，而是在室温下搅拌数小 时后再缓缓加热至回流，否则极易冲料．
关于羧酸酯还原为醇 的原理及操作
• １．金属钠和醇为还原剂（BouveaultBlanc反应） • ２．金属氢化物为还原剂
金属钠和醇为还原剂
• 本反应是将羧酸酯用 金属钠和醇直接还原 生成相应的伯醇，主 要用于高级脂肪羧酸 酯的还原．
O n-C11H23 OEt Na,EtOH toluene n-C11H23 OH
NaBH4-ZnCl2还原
EtOOC OTIPS COOEt Zn(BH4)2 THF EtOOC OTIPS OH