Etherification, internal

Etherification. Ethers of poly(vinyl alcohol) are easily formed. Insoluble internal ethers are formed by the elimination of water, a reaction cataly2ed by mineral acids and alkaU. 

Going to extremes, the reactivity of internal acetylenic triple bonds compared with terminal olefinic double bonds was also checked. Diallyl ethers of commercial 2-butyne-l,4-diol and 3-hexyne-2,5-diol are available in high yield by phase transfer etherification. They are reacted under essentially the same conditions as those described in section 3.1, with the double bond now being in 100 percent excess at the beginning (Eq. 4). 

Normalized to k3 = I. 6 For entries 4 and 7-9, the numbers represent the relative distribution of the substituents between 0-2, 0-3, and 0-6, at degrees of substitution of 0.07, 0.048, 0.14, and 0.034, respectively thus, the relative rate-constants are only approximate. c The relative rate-constant for HO-3 was assumed to be doubled after methylation at HO-2. d The relative rate-constant at one of the secondary hydroxyl groups was assumed to be 0.3 when the other one is substituted. e The relative rate-constant for etherification of the 2-hydroxyethyl group is 10. f The relative rate-constants found are now thought to have been erroneous, as the formation of internal acetals300,301 was not taken into account. 

In addition to alkoxides, carbonyl oxygens have occasionally been recruited to function as nucleophiles in allylic etherification processes. The cyclization reactions of ketones containing internal allylic systems occur through O-allylation under Pd catalysis to give rise to vinyl dihydrofurans203 or vinyl dihydropyrans (Equation (51))204,205 in good yields. 

Etherification using a metal vinylidene has also been combined with G-G bond formation through the reaction of an alkynyl tungsten complex with benzaldehyde (Scheme 14). The addition of an internal alcohol to the incipient /3,/Udialkylvinylidene that is generated leads to dehydration and the formation of a Fischer-type alkylidene complex. Further reactions of this carbene with a range of nucleophiles have provided access to various furan derivatives.374,375... 

A survey of Wacker-type etherification reactions reveals many reports on the formation of five- and six-membered oxacycles using various internal oxygen nucleophiles. For example, phenols401,402 and aliphatic alcohols401,403-406 have been shown to be competent nucleophiles in Pd-catalyzed 6- TZ /fl-cyclization reactions that afford chromenes (Equation (109)) and dihydropyranones (Equation (110)). Also effective is the carbonyl oxygen or enol of a 1,3-diketone (Equation (111)).407 In this case, the initially formed exo-alkene is isomerized to a furan product. A similar 5-m -cyclization has been reported using an Ru(n) catalyst derived in situ from the oxidative addition of Ru3(CO)i2... 

Lukowsky, D. and Peek, R.D. (1998). Time dependent over-uptake of etherificated melamine resins. International Research Group on Wood Preservation, Doc. No. IRGAVP 98-40109. 

Many of the chiral selenium electrophiles have also been employed in cyclization reactions. Various internal nucleophiles can be used and access to different heterocycles is possible. Not only oxygen nucleophiles can be used for the synthesis of heterocyclic compounds, but also nitrogen nucleophiles are widely employed and even carbon nucleophiles can be used for the synthesis of carbacycles with new stereogenic centers. Oxygen nucleophiles have been widely used and some selected examples of selenolactonizations of unsaturated acids 50 and 52 and seleno-etherifications of unsaturated alcohols 54 and 56 are shown in Scheme 10. 

Moreover, the position of the pair of glycidyl groups in DGA and TGDDM enhances the probability of an internal etherification under formation of a morpholine... 

The cyclizations of 85 to 86 and of 87 to 88 represent the simple cases in which the internal nucleophile is the OH group of an alcohol [64,65]. An in situ generated hydroxy group, as in the addition of alcohols to carbonyl compounds, can also participate in phenylseleno-etherification reactions. This is examplified by the conversion of 89 into 90 in the presence of benzyl alcohol [66]. Another type of OH, which gives rise to these reactions is the enolic OH of /1-dicarbonyl compounds. Thus, Ley reported that compounds like 91 and 93 can be transformed into the cyclic derivatives 92 and 94 by treatment with N-PSP 11 in the presence of zinc iodide [67]. The cyclization of 95 to 96 represents a simple example of the selenolactonization process [68, 69]. It is interesting to note that the various cyclization reactions indicated in Scheme 14, which require different electrophilic selenenylating agents, can all be effected with phenyselenyl sulfate [70]. 

If the unsaturated compound contains an internal electron donor center that is able to act as a nucleophile in this process, intramolecular etherification or lactonization is observed [138]. 

Sorbitol is a six-carbon sugar alcohol which contains six hydroxyl groups available for esterification. However, under process conditions that are required for the direct esterification with fatty acids sorbitol undergoes an internal etherification to 1,4-sorbi-tan (anhydro sorbitol), the monoanhydride form of sorbitol, which only contains four hydroxyl groups available for esterification. According to this, the esterification of sorbitol with fatty acids yields sorbitan esters. Sorbitan fatty acid esters can be produced in a one-step process by direct, base-catalyzed reaction of sorbitol with a fatty acid at temperatures of 260 Milder temperature conditions are desirable for more odorless sorbitan esters with lighter color (Figure 4A.43). 

It was stated earlier (p. 9) that internal etherification of monosaccharides yields anhydro-sugars. 1,2-, 2,3-(CC), 34-, and 5,6-epoxide rings, 2,4- and 3,5-propylene oxides (2,4-anhydro-D-glucose (CCI), and 3,5-anhydro-D-xylo-P3Tanose), and 1,4-, 2,5-, and 3,6- (CCII) butylene oxide rings are known. 

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