Dimethylketene

Very Htde is known about the toxicology of other dimeric ketenes. For the dimeric dimethylketene there is equivocal evidence of tumors resulting from massive exposure in rats reported for the P-lactone form (3,3-dimethyl-4-isopropyhdene-2-oxetanone), whereas the symmetric form (2,2,4,4 tetramethylcyclobutane-l,3-dione) induces tumors in mice after lengthy skin appHcations. 

Enamines containing one -hydrogen atom react with the lactone dimer of dimethylketene to form aminocyclohexanediones 116). Polycondensation of acetone diethyl ketal takes place by treating it with morpholine and a catalytic amount of p-toluenesulfonic acid while distilling off the ethanol formed 117-119). The resulting spiran, bicyclo, and cyclooctadienone products differ from the known polycondensation products of acetone, and hence their formation probably involves enamine intermediates 119). 

Benzaldehyde and ketene form alternating copolymers with both cationic and anionic catalysts255. In the case of dimethylketene, crystalline alternating copolymers of... 

Scheme 6.8 gives some examples of ketene-alkene cycloadditions. In Entry 1, dimethylketene was generated by pyrolysis of the dimer, 2,2,4,4-tetramethylcyclobutane-l,3-dione and passed into a solution of the alkene maintained at 70° C. Entries 2 and 3 involve generation of chloromethylketene by dehydrohalo-genation of a-chloropropanoyl chloride. Entry 4 involves formation of dichloroketene. Entry 5 is an intramolecular addition, with the ketene being generated from a 2-pyridyl ester. Entries 6, 7, and 8 are other examples of intramolecular ketene additions. 

Using low-temperature techniques such as those described in the previous section, Haller and Srinivasanmb) obtained direct spectroscopic evidence for the formation of the cyclopropanone. At 4°K infrared bands corresponding to carbon monoxide, dimethylketene, tetramethylethylene, and a compound... 

If simple traps are used, it is necessary to use two in series to condense all the dimethylketene and ethyl acetate. 

The concentration of dimethylketene is determined by titration of an aliquot at ice temperatures with 0.1 N sodium hydroxide using phenolphthalein indicator. Under these conditions, blank determinations indicate that ethyl acetate is not hydrolyzed. 

The identity of the dimethylketene may be determined (and an approximate check made on the concentration) by adding 35 g. of dimethylketene solution to 15 g. of aniline in 75 ml. of ether. After 2-3 minutes, the ether solution is washed with dilute hydrochloric acid, dilute potassium carbonate, then water, and the ether is evaporated. Isobutyroanilide, m.p. 102-103° (103-104° after one recrystallization, no melting-point depression in mixture... 

The preparation of ketenes has been discussed by Hanford and Sauer in Organic Reactions Dimethylketene has been prepared by the treatment of a-bromoisobutyryl bromide with zinc,3 and by the pyrolysis of isobutyrylphthalimide,4 dimethylmalonic anhydride,6 or a-carbomethoxy-a,j3-dimethyl- -butyrolactone. Dimethylketene dimer has been prepared by heating isobutyryl chloride with a tertiary amine. Pyrolysis of the dimer yields dimethylketene.7... 

Dimethylketene rapidly forms an extremely explosive peroxide when exposed to air at ambient temperatures. Drops of solution allowed to evaporate may explode. Inert atmosphere should be maintained above the monomer [1], The peroxide is... 

Autoxidation of dimethylketene with oxygen in ether at —20°C gives the poly (peroxylactone) which as a dry solid is liable to undergo unpredictable and violent detonation. 

The dry powdered condensation product of sodium acz-nitromethanide (2 mol) with dimethylketene dimer exploded violently when added to crushed ice. 

The last [2 + 2] cycloaddition performed onto methylenecyclopropane itself consists of the use of ketene derivatives, particularly of dimethylketene 508 (Table 40, entry 1) [133]. The result is an almost equimolar mixture of the two possible regioisomers 511, albeit no yield has been reported. Anyway, the particular reactivity of methylenecyclopropane was confirmed, since it was found to be around 15 times more reactive than isobutene [133]. The scarce regioselectivity of this cycloaddition was confirmed by the reactions of the same ketene 508 with 2,2-disubstituted methylenecyclopropanes (entries 2 and 3) [134], BCP has also been shown to be reactive towards chloro-substituted ketenes 509 and 510, affording the expected cycloadducts 514 and 515 in mild conditions (entries 4 and 5) [13b],... 

DIMETHYLKETENE /3-LACTONE DIMER (3-Pentenoic acid, 3-hydroxy-2,2,4-trimethyl- /3-lactone)... 

Caution Dimethylketene (3-ladone dimer is a mild but deceptively persistent lachrymator. 

The /3-lactone dimer of dimethylketene can be prepared by pyrolysis of its polyester, which is formed by the base-catalyzed polymerization of dimethylketene.3"6 In addition to the rearrangement of the normal dimer described above,6 the direct dimerization of dimethylketene in the presence of aluminum chloride3 or trialkyl phosphites7 leads to the /3-lactone dimer. 

The /3-lactone dimer of dimethylketene reacts with alcohols, phenols, mercaptans, and amines to form derivatives of 2,2,4-trimethylvaleric acid.3 In this respect it is a more powerful acylating reagent than the normal dimer, tetramethyl-l,3-cyclo-butanedione. The preparation of 2,2,4-trimethyl-3-oxovaler-anilide, for example, is accomplished easily with the lactone dimer, but is extremely difficult with the normal dimer.8... 

In the presence of catalytic amounts of sodium methoxide, dimethylketene /3-lactone dimer is polymerized at moderate temperature to a polyester.3 At higher temperatures (above 100°), disproportionation to the cyclic trimer, hexamethyl-1.3,5-cyclohexanetrione, takes place.9 Addition of a stoichiometric amount of sodium methoxide to the lactone dimer generates the sodium enolate of methyl 2,2,4-trimethyl-3-oxovalerate. This reaction provides a convenient entry into certain ester anion chemistry that formerly required the use of a strong base like tritylsodium.10... 

Although these reactions can be duplicated in most cases with the normal dimer of dimethylketene,11 the more reactive lactone dimer is the preferred reagent. The liquid form of this dimer is convenient to handle. A distinct difference in behavior of the dimethylketene dimers is noted when they are pyrolyzed. The normal dimer is dissociated at 600° to dimethylketene,12 but the lactone dimer is decarboxylated almost quantitatively at 450° to tetramethylallene.13... 

The reaction mixture is then cooled to 35-40° and poured into a stirred solution of 230 g. of sodium chloride and 6.0 g. of sodium acetate in 600 ml. of water at 40°. The mixture is stirred for 15 minutes and then is transferred to a separatory funnel the layers are separated, and the lower, aqueous layer is discarded. The crude product is distilled at reduced pressure through a stainless steel spinning-band column (Note 5). The yield of the /3-lactone dimer of dimethylketene is 122-132 g. (61-67%) b.p. 69-71.5° (14 mm.) (Note 6). The product may be redistilled and the fraction boiling at 119.5-120° (150 mm.), 20d 1.4380, collected. 

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