Tetramethylcyclobutane

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. 

Tetramethylcyclobutan-l,3-dione [933-52-8] M 140.2, m 114.5-114.9°. Crystd from benzene and dried under vacuum over P2O5 in an Abderhalden pistol. 

Irradiation of Z-but-2-ene 8 initiates a cyclodimerization reaction, even without a photosensitizer." This cycloaddition proceeds from a singlet state and is likely to be a concerted, one-step reaction. Bond formation occurs suprafacial with respect to both reactants, whereupon only the tetramethylcyclobutanes 9 and 10 can be formed ... 

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. 

Related investigations of the reaction of diazo compounds with alkyl-substituted thioketones [R2C=S, R = Et, Pr, i-Pi, f-Bu (203) 2,2,4,4-tetramethylcyclobutan-l-one-3-thione (204), and adamantanethione (205,206)] showed that the 3,3-dialkyl-... 

Diimines 3 of 2,2,4,4-tetramethylcyclobutane-l,3-dione were formed by the addition of an excess of primary amines in the presence of titanium(IV) chloride.293- 294 When one equivalent of the amine was used, the mono-imine 2 was isolated. If steric hindrance is a limiting factor, this method is preferred.294 However, an ordinary water separation trap can also be used, omitting the titanium(IV) chloride.295-296 In the latter case, the use of chiral amines such as ( + )-dehydroabietylamine, (+)-ris-2,2-dimethyl-6-phenyl-l,3-dioxan-5-arnine or (-)-a-pheny-lamine, can be used to resolve a racemic mixture of 3,7,7-trimethylbicyclo[3.2.0]hept-2-en-6-one via the corresponding imines.296... 

M TiCl4 in dry toluene (50 mL) was added slowly to a solution of 2,2,4,4-tetramethylcyclobutane-l,3-dione (0.70 g, 5 mmol) and excess r-BuNH2 (3.66 g, 50 mmol) in dry toluene (100 mL) at — 10°C under N2. The mixture was then allowed to reflux for ca. 20 h. The cooled solution was filtered and the residual solid washed thoroughly with benzene. Concentration of the filtrate and sublimation in vacuo gave the bisimine yield 0.63 g (50%) mp 83-84°C. 

Dehalogenation and related reactions have also been employed in the synthesis of many bicyclobutanes. Sodium induced dechlorination of l,3-dichloro-2,2,4,4-letramethylcyclobu-tane (69) gave 2,2,4,4-tetramethylbicyclo[1.1.0]butane (70) in 47% yield,29 while magnesium also converted l-chloro-3-ethoxy-l-phenyl-2,2,4,4-tetramethylcyclobutane (71) into 1-phenyl-2,2,4,4-tetramethylbicyclo[1.1.0]butane (72) in 40% yield.31 Other typical preparations are summarized in Table 3 25-29-31 35... 

To a mixture of Mg turnings (2 g, 83 mmol) and 1,2-dibromocthane (200 pL) in refluxing THE (60 mL) was added over 30 min l-chloro-3-ethoxy-l-phenyl-2,2,4,4-tetramethylcyclobutane (71 19.4 g, 73 mmol). The mixture was refluxed for 5 h, cooled, and poured into H2() (600 mL) containing sat. aq NaHC03 (200 mL). It was then extracted with petroleum ether (4 x) and then dried. Removal of the solvent and distillation of the residue in a molecular still gave the product, which was purified by redistillation through a 15-cm spinning-band column yield 5.5 g (40%) bp 34-36 C (0.1 Torr). 

Aliphatic ketones without any os-hydrogen atoms react smoothly with sulfur tetrafluoride, but usually vigorous reaction conditions are required. Thus, 2,2,4,4-tetramethylcyclobutane-l,3-dione is remarkably resistant towards sulfur tetrafluoride the fluorination takes place at 160 C without charring to give a 73% yield of l,l,3,3-tetrafluoro-2,2,4,4-tetramethylcyclobutane (20).96... 

The photolysis of cyclic ketones, in general, results in homolytic cleavage of the carbon-carbon bond adjacent to the carbonyl function. For details of this process, the reader is referred to the review by Srinivasan.425 Included among the photoproducts are certain oxygen heterocycles, formed by cyclization of reactive intermediates. Thus, cleavage in a cyclic /3-diketone, such as tetramethylcyclobutane-1,3-dione or hexamethylcyclohexane-l,3,5-trione [Eq. (110)] is followed by cyclization on the oxygen atom to form a lactone.426,427 y-Lactone formation is also observed on photolysis of 2,2-diphenylindane-l,3-dione [Eq. (Ill)] in ether, and the process is reversible.428... 

Shurvell175 and collaborators have published the Raman and IR spectra of tetramethylcyclobutane-l-one-3-thione and the fully deuterated derivative. For this compound, the C=0 stretching was observed as a very strong Fermi doublet at 1811-1782 cm-1. For the deuterated species this doublet is red-shifted and was found at 1808-1775 cm-1. The C=S stretching mode was assigned to a band of medium intensity at 1303 cm-1 and 1302 cm-1 in the IR and Raman spectra, respectively, and the same for the deuterated species are found at 1306 cm-1 and 1309 cm-1, respectively. 

The preparation of cyclopropanones by photochemical decarbonylation 8-i°) js illustrated by the formation of 1-ethoxycyclopropanol from the photolysis of tetramethylcyclobutane-l,3-dione (17) in ethanol.9 a> As shown in Scheme 4, the desired hemiacetal is accompanied by a number of side products including ethyl isobutyrate which results from the... 

An interesting but not synthetically useful reaction has been reported by Mloston and co-workers <2002CEJ2184>. The treatment of 2,2,4,4-tetramethylcyclobutan-l,3-dithione with dimethoxycarbene, generated by thermolysis of 2,2-dimethoxy-5,5-dimethyl-2,5-dihydro-[l,3,4]oxadiazole, led to the formation of 4-isopropyl-idene-3,3-dimethyl-thietane-2-thione in trace amounts (2% yield), together with other products (Equation 23). 

A similar [2+2] cyclization has also been performed with 2,2,4,4-tetramethylcyclobutan-l,3-dithione 164 and trifluoromethyltrimethylsilane in tetrahydrofuran (THF), in the presence of tetrabutylammonium fluoride (TBAF) at 0°C and led to the formation of spiro-1,3-dithietane 165 in 70% yield (Equation 23) <2002HCA1644>. 

The 2,2,4,4-tetramethylcyclobutan-l,3-dione ring opens on reaction with allyl bromide under Barbier conditions to form the ketocarbinol in an approximate 60% yield [Eq. (7) 15]. 

Irradiation of 2,2,4,4-tetramethylcyclobutane-I,3-dione in pentane, cyclohexane or dichloro-methane resulted in rapid evolution of carbon monoxide (0 = 0.30) and formation of 2,2,3,3-tetramethylcyclopropanone (1). The reaction was easily monitored by infrared spectroscopy, the photolysis was terminated when the characteristic carbonyl doublet of the cyclo-propanone (1823 and 1843 cm ) reached a constant intensity (10-20% conversion of cyclo-butane-1,3-dione). 

Tetramethyl-2,4-cyclobutanedione See Sodimn l,3-dihydroxy-l,3-bis(oc/-nitromethyl)-2,2,4,4-tetramethylcyclobutan-diide... 

Temperature dependence, photophysical processes, 302-3 stereoselectivity, 326-27 Telra-t-butyltetrahedrane. 385 Tetracene, 254 absorption spectrum, 72, 103 Tetracene radical anion and cation. 103 Tetracycioociene, 423 Tetramethylcyclobutane, 406 TetramethyM,2-dioxeiane, 428. 482-83 Tetrameihylethyiene, 326-27 Tetranitromethane, 465 n.a.a a -Tetraphenylbenzocyclobuiene,... 

There are only a limited number of intermolecular [2 + 2] photocycloaddition reactions known to occur in solution because alkene excited singlet state lifetimes are very short (on the order of 10 ns).708 Direct irradiation of neat but-2-ene, for example, yields tetramethylcyclobutane with stereochemistry suggesting the concerted mechanism (Scheme 6.45).709 Inefficient dimerization (

with efficient E Z isomerization (

[Pg.257]

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