Acetylenic ethers synthesis

In early work, vinyl chloride had been heated with stoichiometric amounts of alkaU alkoxides in excess alcohol as solvent, giving vinyl ethers as products (210). Supposedly this involved a Williamson ether synthesis, where alkaU alkoxide and organic haUde gave an ether and alkaU haUde. However, it was observed that small amounts of acetylene were formed by dehydrohalogenation of vinyl chloride, and that this acetylene was consumed as the reaction proceeded. Hence acetylene was substituted for vinyl chloride and only catalytic amounts of alkaU were used. Vinylation proceeded readily with high yields (211). 

Acetylenic ethers and their analogs in synthesis of heterocycles 89UK1671. 

Alkynylation of zinc-copper compounds has been used for the synthesis of polyfunctional acetylenic ethers [84] and for the preparation of building blocks for pharmaceutically active compounds [85]. Whereas cross-coupling between non-activated iodoalkenes and zinc-copper reagents only proceeds at elevated temperatures and in polar solvents such as NMP or DMPU (60 12 h) [86], alkenyl... 

Based on the elimination reaction, Pericas and coauthors" have developed a method for the synthesis of acetylenic ethers, derived from tertiary alcohols with a bulky alkyl group such as r -butyl and adamantyl. The key step in this synthesis is the dehydrobromination of l-bromo-2-alkoxyethylene 67 with sodium amide in ammonia or lithium diisopropylamide in a hexane-THF solution (equation 39)". ... 

More recent studies have been concerned with the utilization of acetylene functionality and designing a system which would have all the processing criteria of an epoxide system. Materials which process analogously to the state-of-the-art epoxides require a very flexible backbone which will exhibit a low Tg before cure. The study provided a flexible aryl-ether system which Incorporates a phenylsul-fone backbone and has been referred to as ATS. The initial synthesis of ATS Involved the nucleophilic displacement reaction of various leaving groups in the 4,4 positions of diphenylsulfone with the metallic salt of m-hydroxyphenylacetylene. Research in our laboratory for lower cost precursors to ATS has led to the synthesis of bromo end-capped phenylsulfone oligomers via the Ullmann ether synthesis. 

A series of acetylene-terminated, aryl-ether thermoset systems were prepared by an Ullmann ether synthesis involving the condensation of various salts of aromatic bis—diols with m—dibromobenzene. The bromo end-capped oligomers were converted to the acetylene-terminated systems by the catalytically-induced, bromo-displacement reaction with 2-methyl-3-but3m-2-ol, followed by base hydrolysis. 

Shavnya A, Sakya SM, Munich ML, Rast B, DeMello KL, Jaynes BH (2005) Efficient fluoride-mediated synthesis of 5-alkyl amino- euid ether-substituted pyrazoles. Tetrahedron Lett 46 6887-6891. For the regioselective synthesis of 1-alkyl-5-fluoroalkyl-3-hydroxypyrazoles, see Hamper BC, Kurtzweil ML, Beck JP (1992) Cyclocondensation of alkylhydrazines and p-substituted acetylenic esters Synthesis of 3-hydroxypyrazoles. J Org Chem 57 5680-5686... 

Several alternative routes have been suggested, which in some cases are especially useful to prepare alkyl derivatives of EDOT with substitution at the dioxane ring. The most important of these alternative pathways appears to be the acid catalyzed transetherification of 3,4-dimethoxythiophen (or other lower alkoxythiophenes) with vicinal diols. - ° The Williamson ether synthesis can lead to low yields particularly in the case of long chain 1,2-dibromoalkanes due to the competing elimination reactions instead of nucleophilic substitution, resulting in a-olefins or a-acetylenes. Although... 

Now let s draw the forward scheme. Acetylene undergoes hydrogenation in the presence of Lindlar s catalyst to afford ethylene, which can be converted to a diol via a dihydroxylation process. Treatment of the diol with two equivalents of a strong base, such as NaH, gives a dianion. The dianion will react with two equivalents of methyl iodide giving the product (via a Williamson ether synthesis, twice). 

The isophytol side chain can be synthesized from pseudoionone (Fig. 5) using chemistry similar to that used in the vitamin A synthesis (9). Hydrogenation of pseudoionone (20) yields hexahydropseudoionone (21) which can be reacted with a metal acetyUde to give the acetylenic alcohol (22). Rearrangement of the adduct of (22) with isopropenyknethyl ether yields, initially, the aHenic ketone (23) which is further transformed to the C g-ketone (24). After reduction of (24), the saturated ketone (25) is treated with a second mole of metal acetyUde. The acetylenic alcohol (26) formed is then partially hydrogenated to give isophytol (14). 

Although the unsaturated nitrile oxides 124 can be prepared via the aldoxime route (see Scheme 8), the older procedure suffers from the disadvantage that a tenfold excess of allyl alcohol and two additional steps are required when compared to Scheme 15. Therefore, unsaturated nitro ether 123 that can be prepared by condensation of an aldehyde 120 and a nitro alkane followed by Michael addition of alcohol 122, was a useful precursor to nitrile oxide 124 [381. The nitrile oxide 124 spontaneously cyclized to ether 125. This procedure is particularly suitable for the synthesis of tetrahydrofurans (125a-h) and tetrahydropyrans (125i-k) possessing Ar substituents in 72-95% yield (Table 12). The seven-membered ether 1251 was obtained only in 30% yield on high dilution. The acetylenic nitro ether 126 underwent INOC reaction to provide the isoxazole 127. 

Because of its high chemical reactivity, acetylene has found wide use in synthesis of vinyl chloride, vinyl acetate, acrylonitrile, vinyl ethers, vinyl acetylene, trichloro- and tetrachloro-ethylene etc., in oxyacetylene cutting and welding, and as a fuel for atomic absorption instruments. 

The scope and efficiency of [4+2] cycloaddition reactions used for the synthesis of pyridines continue to improve. Recently, the collection of dienes participating in aza-Diels Alder reactions has expanded to include 3-phosphinyl-l-aza-l,3-butadienes, 3-azatrienes, and l,3-bis(trimethylsiloxy)buta-l, 3-dienes (1,3-bis silyl enol ethers), which form phosphorylated, vinyl-substituted, and 2-(arylsulfonyl)-4-hydroxypyridines, respectively <06T1095 06T7661 06S2551>. In addition, efforts to improve the synthetic efficiency have been notable, as illustrated with the use of microwave technology. As shown below, a synthesis of highly functionalized pyridine 14 from 3-siloxy-l-aza-1,3-butadiene 15 (conveniently prepared from p-keto oxime 16) and electron-deficient acetylenes utilizes microwave irradiation to reduce reaction times and improve yields <06T5454>. 

The most convenient method of preparing the flexible (low Tg) system is to employ the Ullmann ether reaction of dibromobenzene and aromatic bis-diols followed by catalytic replacement of the bromine atoms by terminal acetylene groups. A host of commercially available bis-diols have been used in the synthesis with both meta and para dibromobenzene. Low Tg arylether oligomers have been prepared containing sulfone, sulfide, carbonyl, isopropyl and perfluoroisopropyl groups in the backbone (9). 

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