4- acetoacetic acid

Hydrolysis. Ethyl acetoacetate when treated w ith cold dilute sodium hydroxide solution gives the sodium salt of acetoacetic acid. This acid is unstable, and readily breaks down into acetone and carbon dioxide it is of considerable... 

By the ketonic hydrolysis of substituted acetoacetic esters this is brought about by the action of dilute alkali in the cold, followed by acidification and boiling. The free substituted acetoacetic acid is produced, which readily undergoes decarboxylation (since it has a carboxyl and a carbonyl group on the same carbon atom) to give a ketone, for example ... 

The a-acetobutyrolactone, with or without isolation, can be used in the preparation of various 5-substituted 2-butanone derivatives, presumably by decarboxylation of the acetoacetic acid obtained by ring hydrolysis. Simple hydrolysis gives 5-hydroxybutan-2-one (158) and acidolysis with hydrochloric acid gives 5-chlorobutan-2-one in good yields (159). 

Acetoiicetyliition Reactions. The best known and commercially most important reaction of diketene is the aceto acetylation of nucleophiles to give derivatives of acetoacetic acid (Fig. 2) (1,5,6). A wide variety of substances with acidic hydrogens can be acetoacetylated. This includes alcohols, amines, phenols, thiols, carboxyHc acids, amides, ureas, thioureas, urethanes, and sulfonamides. Where more than one functional group is present, ring closure often follows aceto acetylation, giving access to a variety of heterocycHc compounds. These reactions often require catalysts in the form of tertiary amines, acids, and mercury salts. Acetoacetate esters and acetoacetamides are the most important industrial intermediates prepared from diketene. 

Water hydroly2es pure diketene only slowly to give acetoacetic acid [541-50-4] which quickly decomposes to acetone and carbon dioxide, but increasing the pH or adding catalysts (amines, palladium compounds) increases the rate of hydrolysis. The solvolysis of diketene in ammonia results in aceto acetamide [5977-14-0] if used in stoichiometric amounts (99), and P-arninocrotonarnide [15846-25-0] if used in excess (100). 

As the most reactive and economical source of the acetoacetyl moiety, diketene is used as a valuable synthetic intermediate in the manufacture of acetoacetic acid derivatives and heterocycHc compounds which are used as intermediates in the manufacture of dyestuffs, agrochemicals, pharmaceuticals, and polymers. 

The most important use of diketene is for the preparation of derivatives of acetoacetic acid, such as acetoacetate esters, acetoacetamides, and chloroacetoacetates, which have found many uses in life sciences, dyestuffs, adhesives, and coatings. 

In the production of aryhdes of acetoacetic acid, two methods are employed ... 

Fig. 6. Key intermediates derived from benzene. The alkylation reaction shown employs ethylene oxide. Hydrazine condenses with acetoacetic acid to form...

An unusual addition of acetoacetic acid to pyrido[2,3-Z>]pyrazin-2(l//)-one (400) to give (eventually) the 3-acetonyl derivative (401) was postulated (71TH21500) to occur via a cyclic transition state, and the similar addition of oxalacetic ester may occur via a related mechanism. 

A/ -Methoxycarbonyl-2-pyrroline undergoes Vilsmeier formylation and Friedel-Crafts acylation in the 3-position (82TL1201). In an attempt to prepare a chloropyrroline by chlorination of 2-pyrrolidone, the product (234) was obtained in 62% yield (8UOC4076). At pH 7, two molecules of 2,3-dihydropyrrole add together to give (235), thus exemplifying the dual characteristics of 2,3-dihydropyrroles as imines and enamines. The ability of pyrrolines to react with nucleophiles is central to their biosynthetic role. For example, addition of acetoacetic acid (possibly as its coenzyme A ester) to pyrroline is a key step in the biosynthesis of the alkaloid hygrine (236). 

The ease with which acetoacetic acid undergoes thermal decarboxylation... 

In the six-membered series the alkaloids of Punica gr ana turn, isopelletier-ine and methylisopelletierine, have been obtained by treatment of enamines with acetoacetic acid. Isopelletierine (194, R = H) was prepared also by Schopf et al. from d -piperideine (309-311). The reversibility of aldol dimerization (124,131) of enamines has been established by the synthesis of methylisopelletierine (194, R = Me) from dimethyltetrahydroanabasine, accomplished by Lukes and Kovaf (101) (Scheme 19). 

In 1909, Claisen described the first such reaction. Treating 2,5-di-methylisoxazolium methosulfate (140) with potassium benzoate in aqueous media he obtained the iV-methyl-iV-benzoyl amide (141) of acetoacetic acid. ... 

Acetylessigsaure, /. acetoacetic acid, acetylierbar, a. capable of being acetylated, acetylieren, n.f. acetylate,... 

Acetoacetic acid N-benzyl-N-methyiaminoethyl ester -Aminocrotonic acid methyl ester m-Nitrobenzaldehyde... 

A mixture of 4.98 g of acetoacetic acid N-benzyl-N-methylaminoethyl ester, 2.3 g of aminocrotonic acid methyl ester, and 3 g of m-nitrobenzaldehyde was stirred for 6 hours at 100°C in an oil bath. The reaction mixture was subjected to a silica gel column chromatography (diameter 4 cm and height 25 cm) and then eluted with a 20 1 mixture of chloroform and acetone. The effluent containing the subject product was concentrated and checked by thin layer chromatography. The powdery product thus obtained was dissolved in acetone and after adjusting the solution with an ethanol solution saturated with hydrogen chloride to pH 1 -2, the solution was concentrated to provide 2 g of 2,6-dimethyl-4-(3 -nitrophenyl)-1,4-dihydropyridlne-3,5-dicarboxylic acid 3-methylester-5- -(N-benzyl-N-methylamino)ethyl ester hydrochloride. The product thus obtained was then crystallized from an acetone mixture, melting point 136°Cto 140°C (decomposed). 

Nitrobanzaldehyde Acetoacetic acid methyl ester Ammonia... 

Acetoacetic acid N-benzyl-N-methyl-amino ethyl ester Nicardipine... 

Acetoacetic acid methyl ester Nifedipine Acetoacetic ester Dipyridamole Acetoin... 

QHiqO 141-97-9) see Aminophenazone Baclofen Cefotaxime Ceftazidime Chloroquine Cloricromen Cloxacillin Dipyridamole Felodipine Flutoprazepam Hymecromone Kawain Lacidipine Leflunomide Methylthiouracil Nevirapine Nitrendipine Oxacillin Pentoxifylline Propyphenazone Sulfamerazine acetoacetic acid 4-(trifluoromethyl)anilide (C H (,F3N02 351-87-1) see Leflunomide acetoacetyl chloride... 

C2HjNa02, 127-09-3) see a-Acetyldigoxin Dextrothyroxine Fluazacort Fluprednidene acetate Pioglitazone Pyrrocaine sodium acetoacetic acid ethyl ester (C HyNaO, 19232-39-4) see Pentoxifylline sodium acetylide (Na(C2H))... 

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