Halo alkoxides

An a ,/3-epoxycarboxylic ester (also called glycidic ester) 3 is formed upon reaction of a a-halo ester 2 with an aldehyde or ketone 1 in the presence of a base such as sodium ethoxide or sodium amide. Mechanistically it is a Knoevenagel-type reaction of the aldehyde or ketone 1 with the deprotonated a-halo ester to the a-halo alkoxide 4, followed by an intramolecular nucleophilic substitution reaction to give the epoxide 3 ... 

Olefin from the treatment of P-halo-alkoxide with zinc. Br R... 

Many other examples are known of non-selective reactions of halo groups in pyridopyridazines with amines, alkoxides, sulfur nucleophiles such as hydrosulfide and thiolate ions, or thiourea, hydrazine(s), cyanide ion and dimethyl sulfoxide, or on catalytic reduction. 

Purines, N-alkyl-N-phenyl-synthesis, 5, 576 Purines, alkylthio-hydrolysis, 5, 560 Mannich reaction, 5, 536 Michael addition reactions, 5, 536 Purines, S-alkylthio-hydrolysis, 5, 560 Purines, amino-alkylation, 5, 530, 551 IR spectra, 5, 518 reactions, 5, 551-553 with diazonium ions, 5, 538 reduction, 5, 541 UV spectra, 5, 517 Purines, N-amino-synthesis, 5, 595 Purines, aminohydroxy-hydrogenation, 5, 555 reactions, 5, 555 Purines, aminooxo-reactions, 5, 557 thiation, 5, 557 Purines, bromo-synthesis, 5, 557 Purines, chloro-synthesis, 5, 573 Purines, cyano-reactions, 5, 550 Purines, dialkoxy-rearrangement, 5, 558 Purines, diazoreactions, 5, 96 Purines, dioxo-alkylation, 5, 532 Purines, N-glycosyl-, 5, 536 Purines, halo-N-alkylation, 5, 529 hydrogenolysis, 5, 562 reactions, 5, 561-562, 564 with alkoxides, 5, 563 synthesis, 5, 556 Purines, hydrazino-reactions, 5, 553 Purines, hydroxyamino-reactions, 5, 556 Purines, 8-lithiotrimethylsilyl-nucleosides alkylation, 5, 537 Purines, N-methyl-magnetic circular dichroism, 5, 523 Purines, methylthio-bromination, 5, 559 Purines, nitro-reactions, 5, 550, 551 Purines, oxo-alkylation, 5, 532 amination, 5, 557 dipole moments, 5, 522 H NMR, 5, 512 pJfa, 5, 524 reactions, 5, 556-557 with diazonium ions, 5, 538 reduction, 5, 541 thiation, 5, 557 Purines, oxohydro-IR spectra, 5, 518 Purines, selenoxo-synthesis, 5, 597 Purines, thio-acylation, 5, 559 alkylation, 5, 559 Purines, thioxo-acetylation, 5, 559... 

Another method for the synthesis of epoxides is through the use of halo-hydrins, prepared by electrophilic addition of HO—X to alkenes (Section 7.3). When halohydrins are treated with base, HX is eliminated and an epoxide is produced by an intramolecular Williamson ether synthesis. That is, the nucleophilic alkoxide ion and the electrophilic alkyl halide are in the same molecule. 

Epoxides bearing electron-withdrawing groups have been most commonly synthesized by the Darzens reaction. The Darzens reaction involves the initial addition of an ct-halo enolate 40 to the carbonyl compound 41, followed by ring-closure of the alkoxide 42 (Scheme 1.17). Several approaches for inducing asymmetry into this reaction - the use of chiral auxiliaries, reagents, or catalysts - have emerged. 

The reaction of oc-halo ketones (chloro, bromo, or iodo) with alkoxide ions rearranged esters is called the Favorskii rearrangement. 

The Favorskii Rearrangement. When treated with base, a-halo ketones undergo a skeletal change that is similar to the pinacol rearrangement. The most commonly used bases are alkoxide ions, which lead to esters as the reaction products. This reaction is known as the Favorskii rearrangement.84... 

For 1,2-disubstituted epoxides, the regiochemical outcome of nucleophilic attack becomes less predictable. However, in the case of epoxy ethers chelation control can be used to deliver the nucleophile preferentially to the epoxide carbon away from the ether moiety. Thus, treatment of epoxy ether 61 with an imido(halo)metal complex, such as [Cr(N-t-Bu)Cl3(dme)], leads to the clean and high-yielding production of the chlorohydrin 64. The regioselectivity is rationalized in terms of initial formation of a chelated species (62), followed by attack at C-3 to form the more stable 5-membered metallacyclic alkoxide 63 <00SL677>. 

Halodeacylation. Reaction of a (3-keto ester or a p-diketone with NCS or NBS and a base (alkoxide or KOH) results in an a-halo ester or an a-halo ketone by replacement of an acyl group by halogen. 

Reaction between alkoxides and gwt-dihalides (Williamson) or ot-halo ethers... 

When one attempts E2 reactions with a-halo ketones using strong bases such as alkoxides, an interesting rearrangement pathway may occur called the Favorskii rearrangement. In this reaction, the a-halo ketone is converted to an ester. For example, 2-chlorocyclohexanone is converted to the methyl ester of cyclopentanecarboxylic acid by treatment with sodium methoxide in ether ... 

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