Methylthiophene

Dry distillation of sodium laevulinate (I) with phosphorus sulphide gives 2-methylthiophene (II) as the main product  

Mix intimately in a mortar 100 g. of sodium laevulinate, 250 g. of phosphorus sulphide (1) and 50 g. of clean dry sand. Place the mixture in a flask fitted with a condenser for distillation and a receiver (2). Heat the flask with a free flame until the reaction commences, and then remove the flame. When the reaction subsides, continue the heating until distillation ceases. Wash the distillate with 10 per cent, sodium hydroxide solution to remove acidic by-products and steam distil. Separate the crude 2-methyltliiophene from the steam distillate, dry over anhydrous calcium sulphate, and distil from a little sodium. Collect the pure compound at 113° the yield is 30 g. 

1 Central Research Department, Monsanto Chemical Company, Dayton 7, Ohio. a Org. Syntheses, 34, 29 (1954). 

Caution This preparation should be conducted in a well-ventilated hood to avoid exposure to hydrogen sulfide. 

A gravity funnel fitted with a glass rod of suitable diameter is satisfactory for regulating the addition of the slurry. 

Dowtherm A may also be used as a solvent for this reaction. However, because the boiling point (about 265°) is close to the reaction temperature, considerable quantities of Dowtherm distil along with the 3-methylthiophene. The total distillate amounts to 60-75 ml., which after washing and fractionally distilling gives the same yield as with mineral oil. Dowtherm gives a more fluid slurry and final residue and can be easily recovered by distillation at reduced pressure. 

Disodium methylsuccinate was made by hydrogenating a concentrated solution of itaconic acid supplied by Chas. Pfizer and Company in aqueous sodium hydroxide (pH. 8.7) over Raney nickel catalyst at 50 p.s.i. and 80-100°. After the catalyst was removed by filtration, the product was isolated by evaporation of the water and the residue was dried in a vacuum oven at 70-80°. 

With the exception of 2-metallated imidazoles, the metal derivatives of the hetero aromates mentioned have a low thermostability. 2-Lithiothiazole, for example, decomposes at temperatures higher than — 50 °C. In some cases the metallation can induce a cyclofragmentation, e.g. in the following case [154]  

Successful functionalizations therefore can only be carried out with very reactive types of electrophiles , e.g. carbonyl compounds, trialkylchlorosilane and disulfides. 

Although the metallation of thiophene with butyllithium in a THF-hexane mixture proceeds much more easily, ethyllithium in Et20 (prepared from ethyl bromide and lithium) is chosen as the lithiation reagent for the following reasons. 2-Methylthiophene has a boiling point of 112.5 °C, and a distillative separation from the THF and hexane (b.p. between 65 and 70°) would therefore be more difficult and lengthy. Moreover, traces of butanol could be present in the 

Thiophene (88.2 g, 1.05 mol) is added over 20 min to a solution of 1.0 mol of ethyllithium in about 700 ml of Et20 (compare Chap. I, Exp. 1). During, and also for 1 h after this addition the temperature of the mixture is maintained (occassional cooling) between 20 and 25 °C. The thermometer-outlet combination is then replaced by a reflux condenser and the solution is warmed for an additional hour under reflux. Methyl iodide (156.2 g, 1.1 mol) is then added over 20 min, refluxing being continued. After an additional period of 1 h the mixture is cooled to room temperature, after which it is cautiously poured into 500 ml of ice water. After 

If 3-bromothiophene is added to butyllithium at a sufficiently low rate, no 2-lithio-thiophene is formed, because the halogen-lithium exchange is much faster than the vicinal metallation of the bromo compound. Support for the mechanism of trans-metallation was provided by adding an equivalent amount of thiophene to a solution of 3-lithiothiophene in THF, cooled at —30 °C after 1.5 h only the 2-lithio derivative was present in the solution [9]. In Et20 this trans-metallation was very slow. 

Dry distillation of sodium laevulinate (I) with phosphorus sulphide gives 

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Sales of thiophene in the 1990s amount to hundreds of metric tons per year. SuppHes are available worldwide from Synthetic Chemicals Ltd. (SCL) in the United Kingdom and Elf-Atochem SA in France. There is currendy no U.S. producer of thiophene or the principal thiophene derivatives. At these levels of demand, material is shipped in 200-hter dmms and in bulk quantities. Market price is dependent on the level of off-take. 3-Methylthiophene is also available from SCL, but demand is low and even lower in the case of 2-methylthiophene lower production and lower market demand have led to higher prices for these derivatives. 

The thermodynamic properties of thiophene,2-methylthiophene, ° and 3-methylthiophene have been computed from careful measurements of the heat capacity of the solid, liquid, and vapor states, the heat of fusion, the heat of vaporization, and the heat of combustion. From the heat of combustion of thiophene and from thermochemical bond energies, the resonance energy of thiophene has been re-estimated to be only 20 kcal/mole. 

This activation of the ortho position is most strikingly illustrated in the reactivity of 2,5-dimethylthiophene, which competitive experiments have shown to undergo the SnCb-catalyzed Friedel-Crafts reaction more rapidly than thiophene and even 2-methylthiophene. The influence of the reagent on the isomer distribution is evident from the fact that 2-methoxythiophene is formylated and bromi-nated (with A -bromosuccinimide) only in the 5-position. Similarly, although 3-bromo-2-methylthiophene has been detected in the bromi-nation of 2-methylthiophene with bromine, only the 5-isomer (besides some side-chain bromination) is obtained in the bromination of alkylthiophenes with A -bromosuccinimide. ° However, the mechanism of the latter type of bromination is not established. No lines attributable to 2-methyl-3-thiocyanothiophene or 2-methyl-3-chIoro-thiophene could be detected in the NMR spectra of the substitution products (5-isomers) obtained upon thiocyanation with thiocyanogen or chlorination with sulfuryl chloride. 2-Methyl- and 2-ethyl-thiophene give, somewhat unexpectedly, upon alkylation with t-butyl chloride in the presence of Feds, only 5-t-butyl monosubstituted and... 

Complexes 79 show several types of chemical reactions (87CCR229). Nucleophilic addition may proceed at the C2 and S atoms. In excess potassium cyanide, 79 (R = R = R" = R = H) forms mainly the allyl sulfide complex 82 (R = H, Nu = CN) (84JA2901). The reaction of sodium methylate, phenyl-, and 2-thienyllithium with 79 (R = R = r" = R = H) follows the same route. The fragment consisting of three coplanar carbon atoms is described as the allyl system over which the Tr-electron density is delocalized. The sulfur atom may participate in delocalization to some extent. Complex 82 (R = H, Nu = CN) may be proto-nated by hydrochloric acid to yield the product where the 2-cyanothiophene has been converted into 2,3-dihydro-2-cyanothiophene. The initial thiophene complex 79 (R = R = r" = R = H) reacts reversibly with tri-n-butylphosphine followed by the formation of 82 [R = H, Nu = P(n-Bu)3]. Less basic phosphines, such as methyldiphenylphosphine, add with much greater difficulty. The reaction of 79 (r2 = r3 = r4 = r5 = h) with the hydride anion [BH4, HFe(CO)4, HW(CO)J] followed by the formation of 82 (R = Nu, H) has also been studied in detail. When the hydride anion originates from HFe(CO)4, the process is complicated by the formation of side products 83 and 84. The 2-methylthiophene complex 79... 

The addition of 2-me-thylfuran, thiophene, 2-methylthiophene, pyrrole, and 4—methylthiazole to propylene carbonate-LiPF6 or propylene carbonate-THF-LiPF, improved the cycling efficiency [109]. THF-2MeTHF- Li AsF6 with an additional of 2-methylfuran showed the longest cycle life [110, 111]. 

C3H402S, 2H-Thiete 1,1-dioxide C4H602S, 2,5-Dihydrothiophene 1,1-dioxide C4H602S, 2,3-Dihydrothiophene 1,1-dioxide CsHgOjS, 2,5-Dihydro-2-methylthiophene 1,1-dioxide C5H802S, 2,5-Dihydro-3-methylthiophene 1,1-dioxide... 

Synthetic routes that access appropriately substituted thienobenzazepines are also quite important for medicinal chemistry stracture activity relationship studies, and many involve similar bond connectivity strategies. One notable example employs the use of conunercially available 4-methyl-3-nitrophenol (Scheme 6.3). Methylation of the phenol followed by bromination, hydrolysis, and oxidation of the benzylic alcohol afforded aldehyde 9 in quantitative yield. Treatment of this aldehyde with 5-lithio-2-methylthiophene provided, after dehydroxylation, nitro intermediate A in good overall yield. Reduction of the nitro functionality and treatment with phosgene presented the corresponding isocyanide which upon cychzation using aluminum trichloride in a Friedel-Crafts fashion afforded the... 

To probe interactions between active silanol sites and the isothiazolin-based biocides a number of model probes were investigated 12. The adsorbates (1-methylpyrro lidin-2-one, pyridine, pyrrolidine, pyrrole, 2-methylthiophene, 2-octyl-4-isothiazolin-3-one, 4,5-dichloro-2-octyl-4-isothiazolin-3-one and 2-cyclopenen-l -one,) varied in basicity, polarity and 7i-character. The amounts of the adsorbates retained by... 

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