Diketene

As an e.xtension of the oxidative carbonylation with alkyl nitrites, malonate can be prepared by the oxidative carbonylation of ketene (583)[524], Also, the acetonedicarboxylate 585 is prepared by the Pd-catalyzed, alkyl nitrite-mediated oxidative carbonylation of diketene (584)[525],... 

Diketene (635) is converted into 3-phenyl-3-butenoic acid (636) by the reaction of phenylzinc, magnesium, and aluminum reagents via C—O bond clea-vage[495j. 

Boiling acetic acid converts 2-aminothiazole into the 2-acetamido derivative far more easily when catalytic amounts of diketene are added to the reaction mixture (277),... 

Ketenes. Derivatives of the compound ketene, CH2=C=0, are named by substitutive nomenclature. For example, C4Hc,CH=C=0 is butyl ketene. An acyl derivative, such as CH3CH2—CO—CH2CH=C=0, may be named as a polyketone, l-hexene-l,4-dione. Bisketene is used for two to avoid ambiguity with diketene (dimeric ketene). 

TALEIC ANHYDRIDE, MALEIC ACID AND FUMARIC ACID] (Vol 15) diketene container [KETENES, KETENE DITffiRS AND RELATED SUBSTANCES] (Vol 14)... 

Anhydride manufactured by acetic acid pyrolysis sometimes contains ketene polymers, eg, acetylacetone, diketene, dehydroacetic acid, and particulate carbon, or soot, is occasionally encountered. Polymers of aHene, or its equilibrium mixture, methylacetylene—aHene, are reactive and refractory impurities, which if exposed to air, slowly autoxidize to dangerous peroxidic compounds. 

Acyl carbonates (234), alkoxyquinones (235) as vinylogous esters, imino ethers (236), and diketene (237) react with ethyleneimine to give the corresponding acylated ethyleneimines. 

DimeriZa.tlon. A special case of the [2 + 2] cyclo additions is the dimerization of ketenes. Of the six possible isomeric stmctures, only the 1,3-cyclobutanediones and the 2-oxetanones (P-lactones) are usually formed. Ketene itself gives predominandy (80—90%) the lactone dimer, 4-methylene-2-oxetanone (3), called diketene [674-82-8], approximately 5% is converted to the symmetrical dimer, 1,3-cyclobutanedione [15506-53-3] (4) which undergoes enol-acetylation to so-called triketene [38425-52-4] (5) (44). 

For the two most important industrial uses, the gaseous ketene is immediately treated with acetic acid to form acetic anhydride or dimerized to diketene. 

The manufacture of the highly pure ketene required for ketenization and acetylation reactions is based on the pyrolysis of diketene, a method which has been employed in industrial manufacture. Conversion of diketene to monomeric ketene is accompHshed on an industrial scale by passing diketene vapor through a tube heated to 350—600°C. Thus, a convenient and technically feasible process for producing ketene uncontaminated by methane, other hydrocarbons, and carbon oxides, is available. Based on the feasibiHty of this process, diketene can be considered a more stable form of the unstable ketene. 

The second most important use of ketene is in the production of diketene [674-82-8] (3) by controUed dimeri2ation. Diketene has wide utility in the manufacture of pharmaceutical and agricultural chemicals, dyes, pigments and fine chemicals. 

Chemical Properties. Diketene is a reactive and versatile compound which can undergo reaction with a large variety of compounds. These reactions have been reviewed comprehensively (1,5,6,96). 

In most reactions diketene appears to react as acetylketene or one of its tautomeric forms. This is one of the reasons for the correct stmcture of diketene being firmly established only in 1952, 45 years after its discovery (97,98). 

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. 

Diketene is used to C-acetoacetylate aromatic compounds in the presence of aluminum trichloride [7446-70-0]. Benzene [71-43-2] and diketene react to produce acetoacet5lben2ene [93-91-4]. Pyrrole [109-97-7] and diketene react to produce 2-acetoacet5lpyrrole [22441-25-4]. The C-acetoacetyl derivatives of active methylene compounds such as cyanoacetates, malonodinitrile [109-77-3] and Meldmm s acid [2033-24-1], and olefins can be prepared using 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). 

Another important reaction of diketene derivatives is the Hant2sch pyridine synthesis (101). This synthesis is the preparation of 1,4-dihydropyridines (14) starting either from two acetoacetic esters, which react with an aldehyde and ammonia or a primary amine or from 3-aminocrotonates and 2-alkyhdene acetoacetic esters, both diketene derivatives. Several such dihydropyridines such as nifedipine [21829-25-4] (102), nimodipine [66085-59-4] and nicardipine [55985-32-5] exhibit interesting pharmaceutical activity as vasodilators (blood vessel dilation) and antihypertensives (see Cardiovascularagents). 

Six-membered heterocycles with two heteroatoms are prepared by reaction of diketene with a substrate containing a C—O or C—N multiple bond. With carbonyl compounds diketene reacts in the presence of acids to give l,3-dioxin-4-ones. The best known is 2,2,6-trimethyl-4H-l,3-dioxin-4-one [5394-63-8] (15), the so-called diketene—acetone adduct, often used as a diketene replacement that is safer to handle and to transport, albeit somewhat less reactive than diketene itself (103,104), forming acetylketene upon heating. 

Diketene reacts with imines to give l,3-oxa2inones (16) (105). This reaction has been used in the synthesis of the tranquili2er Keta2olam... 

Other six-membered rings with two heteroatoms are also obtained from reaction of diketene with imidates, cyanamides, carbodiimides, isocyanates, oxa2olines, or other multiftmctional compounds. 

Other Reactions of Diketene. Diketene reacts with elemental chlorine to give 4-chloroacetoacetyl chloride [41295-64-17, which can further react to the corresponding esters (111). 

Pyrolysis of diketene at temperatures greater than 400°C gives two molecules of ketene. This method has been used iadustriaHy. At present there is no method to convert diketene efftciendy iato aHene [463-49-0] and CO2, the thermodynamic products. 

Grignard reagents add to diketene ia the presence of cobalt iodide [15238-00-3] C0I2, or palladium [440-05-3] to give 3-methylenecarboxyhc acids, used ia terpenoid and hormone syntheses, as well as monomers for radical copolymers (116,117) (see Hormones Terpenoids). 

Dimeric aldoketenes and ketoketenes of P-lactone stmcture show a chemical behavior which is not much different to that of diketene. Thus nucleophiles add ia similar fashion to give derivatives of 3-ketoacids which are mono- or dialkylated at C-2 (aldo- and ketoketene dimers, respectively), but the reaction can often be slower than with the parent compound and, ia case of long-chain or bulky substituents, may not proceed at all. Other reactions can proceed differendy than those with diketene. For an overview of important reactions of aldoketene and ketoketene dimers see Reference 122. 

---