Chloro-2,3-Dihydropyran

Apparatus 1-1 three-necked, round-bottomed flask, equipped with a vent, a mechanical stirrer and a thermometer. 

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The lithio derivatives of 1,4-dithiin [88] and Z-bis(methylthio)ethene [89] are stable only at very low temperatures fragmentation and elimination of thiol occur if the temperature of the solutions is allowed to rise above — 90 °C. The electron-withdrawing action of chlorine in 5-chloro-2,3-dihydropyran permits a fast and quantitative lithiation with BuLi [89,90] ... 

Experiment 3 describes the a-metallation of 2,3-dihydropyran with the strongly basic system BuLi -But)K TMEDA. If in the / -position an electron-withdrawing substituent is present, the metallation becomes more facile. Thus, 5-chloro-2,3-dihydropyran can be metallated in a short time by the much less basic butyllithium in THF. The high thermostability of the lithio derivative resembles that of 2-lithio-3-halofurans and analogous thiopene derivatives (see Chap. V), but stands in sharp contrast with the trancient existence of species without an oxygen or sulfur atom, e.g. l-halo-2-lithiocycloalkanes [208] and with the instability of arynoids [221]. 

The reaction between vinyl ethers and unsaturated carbonyl compounds, which provides a powerful synthetic route to dihydropyrans, has been adapted to the synthesis of pyran-2-ones (72CC863). 2-Chloro-1,1 -dimethoxyethylene, which is a protected form of chloroketene, undergoes cycloaddition with a number of enones to give the cis or trans isomers of 3-chloro-3,4-dihydro-2,2-dimethoxypyrans (338) and (339) or a mixture of both. Although... 

A simple two-step synthesis of the a-pyrone ring system209 has been applied to the synthesis of bufadienolides.210 Reaction of the known a/3-unsaturated aldehyde (416) with the dimethyl acetal of chloroketen [ClCH=C(OMe)2] gave a 57% yield of the intermediate 2,2-dimethoxy-3 -chloro-3,4-dihydropyran (417) which on reaction with sodium methoxide in DMSO afforded the a-pyrone (418) directly in 64% yield. 

Despite the increasing information on the photochemistry of 2,4-dienones198 and other unsaturated ketones,199 as well as on the ring-chain valence isomerism of halogen-substituted pyran and dihydropyran systems,200-201 the data are still very scarce. The intermediate formation of pyrans valence-isomeric with unsaturated carbonyl compounds in the pyridine syntheses based on reactions of ammonia with aldehydes or ketones, advocated by various authors202-206 (cf. Section II,B,2,f), is still rather speculative. (See also Section II,B,2,e for the valence isomerism of 5-chloro-2,4-dienones with pyrylium chlorides.)... 

The formation of acetals, by the acid catalyzed addition of hydroxyl compounds to a,/8-ethylene ethers is a useful method of protecting the hydroxyl group in reactions effected in basic media.—E 3-Chloro-l-propanol and dihydropyran, with a few drops of coned. HC1, allowed to stand for 3 hrs. with occasional shaking —> 2-(y-chloropropoxy)-tetrahydropyran. Y 78%. (F. e. s. W. E. Parham, E. L. Anderson, Am. Soc. 70, 4187 (1948).)... 

Hydrolysis, of 2-chloro-l,l,2-trifluoro-ethyl ethyl ether, 34, 49 of a,o -dicyano-/3-ethyl-3-methyl-glutarimide, 36, 29 of 3,4-dihydro-2-methoxy-4-methyl-2H-pyran, 34, 71 of dihydropyran, 30, 48 of ethyl 3-benzyl-2-cyano-3-methyl-pentanoate, 36, 8... 

Nucleoside mimetics, NF-substituted derivatives of 4-tosyl-5-polyfluoroaIkyl-l,2,3-triazoles containing fragments of 3-chlorotetrahydrofuran, 3-chloro-tetrahydropyran, tetrahydropyran, dihydrofuran, dihydropyran, or acyclic substituents, were also studied 182-186 [162]. It was demonstrated that some among the studied compounds exhibit a pronounced anti-Epstein-Barr virus (EBV) activity. 

Didiloro-2-oxabicydo[4.1.0]heptane added all at once to a soln. of K in /er/-butanol, and refluxed 24 hrs. 3-chloro-2-fer/-butoxy-2,5,6,7-tetrahydro-oxepin (Y 79%) mixed with dioxane and shaken ca. 12 hrs. at room temp, with 2 N HCl 2H-3,4-dihydropyran-5-carboxaldehyde (Y 92%). L. Skatteb0l, J. Org. Chem. 35, 3200 (1970). 

When 7-chloro-5 - [[(2,3 -difluorophenyl)methyl]thio]thiazolo [4,5 -djpyrimidin-2(3H)-one 175 and p-TsOH in PhMe at 60C was treated with 3,4-dihydropyran and heated with THF, Na2C03, and D-alaninol afforded 5-[[(2,3-difluorophenyl)methyl]thio] -7- [[(1 R)-2-hydroxy-1 -methylethyljamino] -3 -... 

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