Cyclic ether five-membered

Cyclic ethers (five-membered ring) 1080-1060 9.26-9.43 s m asym COC str... 

This is a special case of 0-12. The base removes the proton from the OH group and the epoxide then attacks in an internal Sn2 reaction.589 Many epoxides have been made in this way.590 The method can also be used to prepare larger cyclic ethers five- and six-membered rings. Additional treatment with base yields the glycol (0-7). 

This reaction can be used to synthesize cyclic ethers with larger rings. The difficulty lies in preventing the base (added to deprotonate the alcohol) from attacking and displacing the halide. 2,6-Lutidine, a bulky base that cannot easily attack a carbon atom, can deprotonate the hydroxyl group to give a five-membered cyclic ether. Five-, six-, and seven-membered (and occasionally four-membered) cyclic ethers are formed this way. 

Diols react mtramolecularly to form cyclic ethers when a five membered or six membered ring can result... 

Conversion to dialkyl ethers (Sec tion 15 7) On being heated in the presence of an acid catalyst two molecules of a primary alcohol combine to form an ether and wa ter Diols can undergo an intramo lecular condensation if a five membered or six membered cyclic ether results... 

During electrochemical fluorination retention of important functional groups or atoms in molecules is essential. Acyl fluorides and chlorides, but not carboxylic acids and anhydrides (which decarboxylate), survive perfluorination to the perfluorinated acid fluorides, albeit with some cyclization in longer chain (>C4) species [73]. Electrochemical fluorination of acetyl fluoride produces perfluoro-acetyl fluoride in 36-45% yields [85]. Electrochemical fluorination of octanoyl chloride results in perfluorinated cyclic ethers as well as perfluorinated octanoyl fluonde. Cyclization decreases as initial substrate concentration increases and has been linked to hydrogen-bonded onium polycations [73]. Cyclization is a common phenomenon involving longer (>C4) and branched chains. a-Alkyl-substituted carboxylic acid chlorides, fluorides, and methyl esters produce both the perfluorinated cyclic five- and six-membered ring ethers as well as the perfluorinated acid... 

An illustration of the tendency of alkane 1,2- and alkane-1,3-dicarboxylie acids to a ring closure during the reaction with sulfur tetrafluoride is the reaction of propane-1,2,3-tricarboxylie acid The corresponding six- and five-membered cyclic ethers are formed in a 1 4 ratio [211] (equation 106)... 

On treatment with sulfur tetrafluoride followed by hydrolysis, D- and L-hy droxysuccimc acids and D-tartanc acid give complex mixtures of products in which the predominant components are five-membered cyclic ethers, derivatives of 2,2,5,5-tetrafluorotetrahydrofuran [209, 272] (equation 108)... 

To verify the generality of the cyclization of iodopyrazolecarboxylic acids, copper p-phenylbenzoylacetylide was used in the reaction with 3-iodo-l-methylpyra-zole-4-carboxylic acid. The assumed intermediate, alkynylpyrazolylcarboxylic acid, has a distribution of the electron density which is the most favorable for closure of the five-membered cyclic ether. However, the reaction leads only to the 5-lactone (Scheme 120). 

If the carbonyl and the hydroxyl group are in the same molecule, an intramolecular nucleophilic addition can take place, leading to the formation of a cyclic hemiacetal. Five- and six-membered cyclic hemiacetals are relatively strain-free and particularly stable, and many carbohydrates therefore exist in an equilibrium between open-chain and cyclic forms. Glucose, for instance, exists in aqueous solution primarily in the six-membered, pyranose form resulting from intramolecular nucleophilic addition of the -OH group at C5 to the Cl carbonyl group (Figure 25.4). The name pyranose is derived from pyran, the name of the unsaturated six-membered cyclic ether. 

A similar mechanism may also be suggested for the thermal fragmentation of cyclic five-membered a-sulfonyl ethers to sulfur dioxide, alkenes and carbonyl compounds (equation 33)101 103 as well as for the analogous rearrangement and fragmentation of trithioorthoacetate-S, S-dioxides (equation 34)104. 

This time the cyclisation was more successful, the five membered cyclic ether (25) being formed in excellent yield in acid. 

Sulfenoetherification. The reagent in combination with trifluoromethane-sulfonic acid converts suitably unsaturated alcohols into five- to seven-membered cyclic ethers. The cyclization is considered to involve an intermediate episulfonium ion. 

Reduction of lactols to ethers. Five- and six-membered lactols are reduced to cyclic ethers by (C2H5)3SiH and trifluoroacetic acid. The reaction can be highly stereoselective (equation I). 

Attempted preparation of the aldehyde precursor of the five-membered ether product through oxidation of the corresponding alcohol led not to the aldehyde, but instead the cyclic ether itself (Eq. 9.104). Evidently the cyclization reaction is facile in this case. 

Allenyl ethers 202, which are easily accessible by the methods described in Chapter 1, consequently lead to cyclic ethers 203. The alkoxyallenes were much more reactive than the alkylallenes from the previous example. Thus the amount of catalyst could be reduced to 0.1mol% and 820 turnovers were reached. Five- to seven-membered rings were isolated (Scheme 15.65) [131],... 

Figure 9.7 Six- and five-membered cyclic ethers. The stable ring structures which are adopted by hexoses and pentoses are five- or six-membered and contain an oxygen atom. They are named as derivatives of furan or pyran, which are the simplest organic compounds with similar ring structures, e.g. glucofuranose or glucopyranose for five-or six-membered ring structures of glucose respectively.

Reductions of five-membered cyclic sulfones with lithium aluminum hydride were run in refluxing ether and of other sulfones in refluxing ethyl butyl ether (92°) (yields 12-92%). Benzothiophene-1,1-dioxide was reduced at the double bond as well, giving 2,3-dihydrobenzothiophene in 79% yield after 18 hours of refluxing in ether [687],... 

Reduction of cyclic five-membered ethylene monothioketals with calcium in liquid ammonia cleaves the bond- between carbon and sulfur and yields alkyl -mercaptoethyl ethers (7-88%) [795]. Cyclic five-membered ethylene dithioketals (ethylenemercaptoles) afford, analogously, alkyl -mercaptoethyl thioethers (yields 85%) [795]. 

Finally, it should be pointed out that in some cases epoxides are opened by a remote hydroxy group within the molecule to give the five-membered ethers [41]. We are currently investigating how the conformation of an open chain epoxy polyol might be responsible for cyclic ether formation [43]. 

Ab initio calculations indicated that introduction of a cyclic ether to the phenyl group of sildenafil derivatives 60 might enhance coplanarity of the molecule. The torsional angles were calculated to be 2-3° for sildenafil analogues with a five-membered ether ring and 12-16° for the derivatives of 60 with a six-membered ether ring. The least planar molecules are the most active enzyme inhibitors <2001BMC1609>. 

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