With alkoxides

As crowding at the carbon that bears the leaving group decreases the rate of nude ophilic attack by the Lewis base increases A low level of steric hindrance to approach of the nucleophile is one of the special circumstances that permit substitution to pre dominate and primary alkyl halides react with alkoxide bases by an 8 2 mechanism m preference to E2... 

We already know what happens when simple esters are treated with alkoxide bases— they undergo the Claisen condensation (Section 211) Simple esters have s of approximately 22 and give only a small amount of enolate when treated with alkoxide bases The small amount of enolate that is formed reacts by nucleophilic addition to the carbonyl group of the ester... 

Difluoroethanol is prepared by the mercuric oxide cataly2ed hydrolysis of 2-bromo-l,l-difluoroethane with carboxyHc acid esters and alkaH metal hydroxides ia water (27). Its chemical reactions are similar to those of most alcohols. It can be oxidi2ed to difluoroacetic acid [381-73-7] (28) it forms alkoxides with alkaH and alkaline-earth metals (29) with alkoxides of other alcohols it forms mixed ethers such as 2,2-difluoroethyl methyl ether [461-57-4], bp 47°C, or 2,2-difluoroethyl ethyl ether [82907-09-3], bp 66°C (29). 2,2-Difluoroethyl difluoromethyl ether [32778-16-8], made from the alcohol and chlorodifluoromethane ia aqueous base, has been iavestigated as an inhalation anesthetic (30,31) as have several ethers made by addition of the alcohol to various fluoroalkenes (32,33). Methacrylate esters of the alcohol are useful as a sheathing material for polymers ia optical appHcations (34). The alcohol has also been reported to be useful as a working fluid ia heat pumps (35). The alcohol is available ia research quantities for ca 6/g (1992). 

The very high reactivity of the P—Cl bonds in (4) forms the basis for the now well-known macromolecular substitution method, which has been used to synthesize polymers of types (1) and (2) and some polymers that are hybrids of these and (3). The method involves nucleophilic reactions of (4), and to some extent of its difluoro analogue, with alkoxides or amines. 

Dichloropyridazine 1-Oxide produces both isomers with alkoxides. However, the ratio is dependent on the size of the alkoxy group. In the reaction with sodium methoxide 80% of 6-chloro-3-methoxypyridazine 1-oxide and 7.5% of 3-chloro-6-methoxypyridazine 1-oxide are formed. Similar results are also obtained with sodium ethoxide, while sodium propoxide affords only 6-chloro-3-propoxypyridazine 1-oxide. Amines react similarly, while only chlorine at the 3-position can be substituted with an azido group to give 3-azido-6-chloropyridazine 1-oxide. 

Chloro-5-arylisoxazoles undergo nucleophilic displacement with alkoxide ion. Halogen atoms in the 5-position of the isoxazole nucleus are readily displaced if an activating group is present in the 4-position (63AHC(2)365). 

Azaindoles formation, 2, 599 NMR, 4, 499 1-Azaindolizine nucleophilic attack, 4, 458 1-Azaindolizine, 5-chloro-reaction with alkoxides, 4, 458... 

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... 

This group has also developed two ring-contraction systems of potential use in crown synthesis. In the first of these, extrusion of a phenylphosphine oxide unit results from treatment with alkoxide ion. In the second, similar conditions initiated decarbonyla-tion of a bis-pyridyl ketone Despite the apparent potential of these methods for crown synthesis, direct formation of crowns by processes which involve them do not appear to have enjoyed great success thus far. 

Alkaline alcoholysis ol hexafluoropropylene leads to alkyl 2,3,3,3-tetrafluoro-propionates. Subsequent treatment of these with acids and then with alkoxides gives dialkyl fluoromalonates [34, J5] (equation 36). 

The nucleophilic reaction of bromotrifluoroethene with alkoxides yields not only the expected addition and addition-elimination products but also a product from a bromophilic reaction of the carbanion intermediate [6] (equation 3) Similar are the reactions of sodium phenoxide with perfluorovinyl ethers in the presence of hexachloroethane or selected vicinal dibromoperfluoroalkanes The intermediate carbanion is trapped in high yield by these sources of Cl or Br, which suggests a... 

The reaction of chlorodifluorotnethane with alkoxide ions generated in low concentration from halide ions and epoxides [28, 29] is an interesting, higher temperature method that gives good to excellent yields of gem-difluorocyclo-propanes from just moderately nucleophilic olefins (equation 9)... 

Secondary and tertiary alkyl halides are not suitable, because they react with alkoxide bases by E2 elimination rather than by Sn2 substitution. Whether the alkoxide base is primary, secondary, or tertiary is much less important than the nature of the alkyl halide. Thus benzyl isopropyl ether is prepared in high yield from benzyl chloride, a primary chloride that is incapable of undergoing elimination, and sodium isopropoxide ... 

On treatment with alkoxide bases, esters undergo self-condensation to give a p-keto ester and an alcohol. Ethyl acetate, for exanple, undergoes a Claisen condensation on treatment with sodium ethoxide to give a p-keto ester known by its common nane ethyl ace-toacetate (also called acetoacetic ester) ... 

P-Keto esters are characterized by pK s of about 11 and are quantitatively converted to their- enolates on treatment with alkoxide bases. 

The Gabriel-Colman reaction has been used to prepare 3-alkyl isoquinoline 1,4-diols. Phthalimides 8 and 9 rearrange as expected when treated with alkoxides. Further treatment with sodium ethoxide results in decarboxylation and the expected isoquinolinone 1,4-diols 12 and 13. 

From the standpoint of geometrical considerations, the major difference is in the far greater steric requirements of the nitro group. This could result in either primary or secondary steric effects. Nevertheless, primary steric effects do not seem to be necessarily distinguishable by direct kinetic comparison. A classic example is the puzzling similarity of the activation parameters of 2-chloropyrimidine and 2,6-dinitrochlorobenzene (reaction with piperidine in ethanol), which has been described by Chapman and Rees as fortuitous. However, that nitro groups do cause (retarding) primary steric effects has been neatly shown at peri positions in the reaction with alkoxides (see Section IV,C, l,c). 

Transetherifications of alkoxy and aryloxy heterocycles with alkoxides have been observed (Sections III,B and IV, B), In 2,4-dialkoxyquinazoline, only the 4-alkoxy group exchanges. When 3-chloro-6-methox3rpyridazine was treated with sodium alkoxides. 

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