Diketene dimerization

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). 

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. 

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. 

Higher dimeric ketenes are flammable but have higher flash points and are less reactive than diketene. Almost no data are available. Diketene can be disposed of by incineration, preferably after dilution with an inert solvent such as toluene. Higher ketene dimers can also be incinerated. 

On the other hand y-pyrones or 1,3-diketones could be obtained from the reactions of ketone derived enamines with diketene 423-426). The addition of dimethyl ketene dimer to aldehyde or ketone derived enamines produced cyclohexanediones 425,426). 

Laboratory Chemical Disposal Co. Ltd., confid. information, 1968 Presence of mineral or Lewis acids, or bases including amines, will catalyse violent polymerisation of this very reactive dimer, accompanied by gas evolution [1], Sodium acetate is sufficiently basic to cause violent polymerisation at 0.1% concentration when added to diketene at 60°C [2],... 

Since reaction of wood with acetic anhydride leads to the formation of acetic acid by-product, which must be removed from the wood, there has been some interest in the use of ketene gas for acetylation (Figure 4.4a). Ketene, for reaction with wood, is produced by pyrolysis of diketene. Provided that the wood contains no moisture, no acetic acid by-product is produced. However, ketene presents handling problems it is very toxic and explosive, and it also has a tendency to dimerize. A comprehensive series of studies of ketene-based acetylation has been performed in Latvia and this work has been reviewed by Morozovs etal. (2003). Hardwoods have been found to be more reactive to ketene than softwoods and the optimal temperature for reaction has been determined as 47 °C. Application of vacuum and treatment of wood with ammonia solution has been used to remove the excess ketene. The reaction of wood with liquid diketene was also studied, with a WPG of 35 % being obtained after reaction for 3 hours at 52 °C. 

In 1985, Kwiatkowski et al. reported a tetramethyl ethylenediamine (TMEDA)-catalyzed dimerization of ketene giving the interesting compound 4-methylene-oxetane-2-one (diketene). This substance can be hydrogenated by either Pd/C to racemic p-BL as well as by asymmetric catalysis according to Takaya et al. using Ru complexes of (5)-BINAP as catalyst, with an ee of 92% [111] (Fig. 39). 

The only four- - six-membered ring interconversions of any real synthetic significance are those involving diketene. Base-catalyzed dimerization of diketene is a long-established and efficient method for the preparation of dehydroacetic acid (equation 161), while mild treatment with water in the presence of tertiary amine bases gives 2,6-dimethyl-4-pyrone (equation 162). 1,3-Dioxins are obtained from the acid-catalyzed condensation of diketene with ketones (equation 163). 

Oxidation of a 1, 4,6-tetraketone (I).1 Oxidation of oxalyldiacetone (1) with iodosobenzene diacetate results in 2. Oxidation of 1 with lead tetraacetate gives dchydroacetic acid (3), previously obtained by dimerization of diketene. 

Base-catalyzed dimerization of diketene (167) efficiently yields dehydroacetic acid (168) treatment of diketene with aqueous triethylamine gives 2,6-dimethyl-4-pyrone (169). 

Stainless steel 302 -diketene container [KETENES, KETENE DIMERS AND RELATED SUBSTANCES] (Vol 14) - [CORROSION AND CORROSION CONTROL] (Vol 7)... 

Ketene has a boiling point of—56° and normally would be stored under pressure in steel cylinders. However, this is not possible because ketene is unstable with respect to formation of a dimer known as diketene ... 

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

Six-Membered Heterocycle Ring Formation. Heterocycle formation involving diketene usually involves acetoacetylation of a substrate, followed by intramolecular condensation. Diketene itself readily dimerizes through self-condensation forming mainly dehydro acetic acid [771-03-9] (DHA) (13). Dehydroacetic acid and sodium dehydro acetate [4418-26-2] are used as preservatives for foods and cosmetics. DHA is found as an unwanted by-product in many diketene reactions, but can be obtained intentionally by dimerizing diketene in the presence of pyridine [110-86-1] in benzene, diazabicyclo[2.2.2]octane [280-57-9] (DABCO), and other basic catalysts. 

Cmde diketene obtained from the dimerization of ketene is dark brown and contains up to 10% higher ketene oligomers but can be used without further purification. In the cmde form, however, diketene has only limited stability. Therefore, especially if it has to be stored for some time, the cmde diketene is distilled to > 99.5% purity (124). The tarry distillation residue, containing triketene (5) and other oligomers, tends to undergo violent spontaneous decomposition and is neutralized immediately with water or a low alcohol. Ultrapure diketene (99.99%) can be obtained by crystallization (125,126). Diketene can be stabilized to some extent with agents such as alcohols and even small quantities of water [7732-18-5] (127), phenols, boron oxides, sulfur [7704-34-9] (128) and sulfate salts, eg, anhydrous copper sulfate [7758-98-7]. 

While diketene remains a very important synthetic precursor, there has been increasing interest in the chemistry of a-methylene-/3-lactones, 3-methylene-2-oxetanones. However, unlike diketene, which can be readily synthesized by the dimerization of aldehydic ketenes, there are few methods for the synthesis of a-methylene-/3-lactones in the literature. Recent strategies for the preparation of the compounds are discussed in Section 2.05.9.2. The kinetic resolution of racemates of alkyl-substituted a-methylene-/3-lactones has been carried out via a lipase-catalyzed transesterification reaction with benzyl alcohol (Equation 21) <1997TA833>. The most efficient lipase tested for this reaction was CAL-B (from Candida antarctica), which selectively transesterifies the (A)-lactone. At 51% conversion, the (R)-f3-lactone, (R)-74, and (A)-/3-hydroxy ester, (S)-75, were formed in very high enantio-selectivities (up to 99% ee). 

The dimerization of ketene leads to the formation of a lactone ( diketene ), the dimerization of dimethylketene furnishes a cyclobutanedione. In Figure 6.25, diketenes were introduced as reagents acylating alcohols to acetylacetates. 

Dehydration of primary nitroalkanes with phenyl isocyanate or acetic anhydride in the presence of catalytic triethylamine affords nitrile oxides, which may be trapped as their 1,3-dipolar cycloadducts or allowed to dimerize to the corresponding furoxans. Other dehydrating agents that have been used include diketene, sulfuric acid and, when the a-methylene group is activated by electron-withdrawing groups, boron trifluoride in acetic anhydride, trifluoroacetic anhydride with triethylamine, and nitric acid in acetic acid. 

An important method for the preparation of /3-keto esters is by the action of alcohols on ketene dimers in the presence of acid catalysts. Diketene and alcohols give acetoacetic esters in 60-80% yields. Dimers of higher ketenes are made by dehydrohalogenation of acyl halides and are converted to /S-keto esters in one operation (cf. method 245). 

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