Ketenes dimerization reactions

Phosphines Phosphines have also been utilized as effective asymmetric catalysts for ketene dimerization reactions. Initial reports by Elam [60] and Bentrude and Johnson [61] demonstrated that trialkylphosphites were capable of acting as effective nucleophilic catalysts in the dimerization of dimethylketene, while Kerrigan and coworkers also demonstrated that disubstituted ketenes could be dimerized with catalytic quantities of trialkylphosphines (Scheme 3.27) [62]. Kerrigan and coworkers extended this... 

Two extreme mechanisms can be envisaged (Scheme 12), concerted [2 + 2] cycloaddition or the more generally accepted formation of a dipolar intermediate (164) which closes to a /3-lactam or which can interact with a second molecule of ketene to give 2 1 adducts (165) and (166) which are sometimes found as side products. In some cases 2 1 adducts result from reaction of the imine with ketene dimer. 

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). 

The diion mechanism c has been reported for at least some of the reae-tions in categories 3 and as well as some ketene dimerizations. For example, the rate of the reaction between l,2-bis(trifluoromethyl)-l,2-dicyanoe-thene and ethyl vinyl ether was strongly influenced by changes in solvent polarity.Some of these reactions are nonstereospecific, but others are stereo-specific. As previously indicated, it is likely that in the latter cases the di-ionic... 

Ketenes can be prepared by treatment of acyl halides with tertiary amines. The scope is broad, and most acyl halides possessing an a hydrogen give the reaction, but if at least one R is hydrogen, only the ketene dimer, not the ketene, is isolated. However, if it is desired to use a reactive ketene in a reaction with a given compound, the ketene can be generated in situ in the presence of the given compound. ... 

Route (b), based on an aliphatic Friedel-Crafts reaction, gives a good yield of (31) which is duly acylated with ketene dimer. 

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. 

Ketene dimerization is the principal synthetic route to 4-methylene-2-oxetanones. This reaction proceeds very satisfactorily for ketene and methylketene, but disubstituted ketenes dimerize only to cyclobutane-1,3-diones. The cycloaddition reaction of r-butylcyanoketene to ketene and to methylketene gives a-cyanoalkylidene-/3-lactones in about 40% yield in addition to the cyclobutane-1,3-dione dimer of f-butylcyanoketene. A mechanism has been proposed for the formation of both types of dimers from a common zwitterionic intermediate (equation 111), with the relative amount of each product determined by the configurational equilibrium of the intermediate (80JOC4483, 75JOC3417). 

The 1,4-diazepine system has also been synthesized by the reactions of 1,2-diamines with various other reagents, e.g. ketene dimers (68CRV747, p. 778) 1,3-diynes <74AHC(17)1, p. 5), bis(cyanomethylene)-l,3-dithietanes (76T483). 

The metal-free eyclobutane-1,2-dioxime can be generated by oxidative displacement. It is interesting to note that, unlike ketene dimerization, head-to-head dimerization takes place here. The chromium ketenimine complex 20 is prepared by reaction of the Fischer-type chromium carbene complex with alkyl isocyanides.60 A cyclobutane-1,2,3,4-tetraimine 24 has been reported from the reaction of the ketenimine phosphonium ylide 22.61 Bisimine 23 has been proposed as the intermediate in this transformation. 

Allene ketene cycloadditions are of greater synthetic utility than cither mixed allene dimerization or mixed ketene dimerization. In this class of reaction the ketene is the more reactive species and homodimerization of ketene can be minimized by use of excess allene. Such cycloadditions always result in 2-alkylidenecyclobutanones with the sp carbons of both moieties forming the initial bond. In substituted allenes and ketenes, mixtures of stereoisomers of 2-alkylidenecyclobutanones are obtained with very little stereoselectivity, the stereoisomers arise from cisUrcins isomerism in the cyclobutane ring and EjZ isomerism of the exocyclic double bond. In unsymmetrically substituted allenes some regiochemical preference for ketene cycloaddition is observed. Examples of dimethylketene allene cycloadditions are summarized in Table 1,2... 

The advantage of using the photocycloaddition of pentacarbonylcarbenechromium complexes over the ketene cycloaddition method is the absence of ketene dimerization and the avoidance of use of excess alkene in the former method. Also, the mild reaction conditions associated with the use of chromium carbene complexes avoids epimerization and thermodynamic equilibration of 2-monosubstituted cyclobutanones. 

The reaction has been extended to a synthesis of terpenes from / -methyl-/S-propiolactone, available by hydrogenation of ketene dimer.9 Example ... 

In a 500-cc. round-bottomed, three-necked flask fitted with a reflux condenser, dropping funnel, and a mercury-sealed stirrer (Note 1) is placed a solution of 46 g. (0.5 mole) of dry aniline in 125 cc. of pure dry benzene. Stirring is started, and a solution of 42 g. (0.5 mole) of ketene dimer (p. 64) in 75 cc. of pure dry benzene is added dropwise over a period of half an hour. The reaction mixture is then heated under reflux on the steam bath for one hbur. 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 cc. of hot 50 per cent aqueous alcohol from which the aceto-acetanilide separates on cooling. The mixture is cooled to 0° before filtration. A second crop of crystals can be obtained by adding 250 cc. of water to the mother liquor and cooling again (Note 2). The total yield of product, m.p. 82-83.5°, is 65 g. (74 per cent of the theoretical amount). Further purification by recrystallization from 300 cc. of 50 per cent alcohol yields 55 g. of a product which melts at 84-85°. 

Acetoacetanilide has been prepared by the reaction of aniline with ethyl acetoacetate 2 3 and by the reaction of ketene dimer with aniline.4... 

A new photoreaction is described for the tricyclic triazoline shown in Scheme 44, which upon irradiation in methanol gives a pyrrole methyl ester205 by retro Diels-Alder reaction of an intramolecular pyrrole-ketene Diels-Alder adduct (88) formed from the diradical (Scheme 154).205 In benzene, ketene dimerization occurs. 

Figure 1. Postulated sizing reactions of (a) alkyl ketene dimers and (b) alkyl succinic anhydrides. R. and R are short alkyl chains. Cell-OH represents cellulose.

Irradiation of tetramethyl-1,3-cyclobutanedione in nonhydroxylic solvents results in decarbonylation as the major course of reaction with g-cleavage being observed as a minor reaction path. A low yield of the lactone [115] has also been reported (73) however, since this material might result from dimerization of dimethyl-ketene, it may not be a primary photoproduct (i.e., ketene dimer is isolated from irradiation of [69]. 

Turro and his coworkers were among the first to recognize the generality of the correlation between photochemical reactivity and mass spectrometric fragmentation reactions. s.ise) "phe photochemical reactivity of ketene dimers. Benzylcyclopropane and nortricyclanone g... 

Ketene, H,C = C = 0, has been obtained by the pyrolysis of many compounds containing the CHjCO—group. However, its preparation from acetone has been the most successful from the standpoint of the laboratory and is carried out by passing the vapors through a combustion furnace at 650° (30%) or over a hot Chromel A wire filament at 700-750° (90%). The product is contaminated with ethylene, carbon monoxide, and methane. It may be purified by dimerization followed by depolymerization (cf. method 246). More often than not, since ketene dimerizes readily, it is passed directly from the generator into a reaction vessel for immediate consumption. 

Ketene acetals, preparation, 267, 269 Ketene dimers, depolymerization, 407 reaction with alcohols, 483... 

The requisite a-diazo thiol esters are conveniently prepared by using the "detrifluoroacetylative" diazo transfer strategy previously developed in our laboratory. Cycloadditions are best carried out by using as little as 0.006 equiv of rhodium(II) acetate to promote the thia-Wolff rearrangement. Reactions involving the more nucleophilic ketenophiles proceed smoothly in refluxing dichloromethane (40°C), while cycloadditions with less reactive partners are best accomplished in 1,2-dichloroethane (83°C). As is standard for ketene cycloadditions, the optimal protocol involves slowly adding a solution of the diazo thiol ester to a solution of the ketenophile and catalyst in order to minimize competitive ketene dimerization. 

The reaction probably takes place through the ketene dimer it is diecuaaed in eection VII... 

The kinetics of the addition of ketene dimer to aromatio amines havo been mvostigated. The dimers of the higher alkylketenes do not react with secondary amines or with phmiyUiydraiine, but their quantitative reaction with ethylamine hae been used for their determination, 2,3-J)ihydro-A, A diiii thyl-p-tketene dimer to form 7.8-dihydio-2,6 dimethy1-chromone. 

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