Oxygen nucleophiles reactions

In reactions 1 and 2, the species attacking the haloalkane is an anionic oxygen nucleophile. Reaction 3 shows that a halide ion may function not only as a leaving group, but also as a nucleophile. 

This realization led me to study related possible intermolecular electrophilic reactions of saturated hydrocarbons, Not only protolytic reactions but also a broad scope of reactions with varied electrophiles (alkylation, formylation, nitration, halogenation, oxygenation, etc.) were found to be feasible when using snperacidic, low-nucleophilicity reaction conditions. 

Reactions with Carbon and Oxygen Nucleophiles, and Other Reactions... 

Displacement reactions with oxygen nucleophiles are of potential commercial interest. Alkaline hydrolysis provides 2-fluoro-6-hydroxypyridine [55758-32-2], a precursor to 6-fluoropyridyl phosphoms ester insecticides (410—412). Other oxygen nucleophiles such as bisphenol A and hydroquinone have been used to form aryl—pyridine copolymers (413). 

Reaction with Oxygen Nucleophiles. In the presence of strong acids, eg, H2SO4, HBF, or BF, aziridines react with alcohols to form P-amino ethers (93) ... 

The reaction of a hydroperoxide with 2-methylaziridine [75-55-8] has been described (94). The reaction of ethyleneknine with phenols (95) and carboxyHc acids (96,97) produces ethylamine ethers and esters, respectively. However, these reactions frequentiy yield product mixtures which contain polyaminoalkylated oxygen nucleophiles and polymers, in addition to the desked products (1). The selectivity of the reaction can often be improved by using less than the stoichiometric amount of the aziridine component (98,99). 

Nucleophilic substitution of the chlorine atom in 2-chloropyrazine and 2-chloroquinoxa-lines has been effected with a variety of nucleophiles, including ammonia and amines, oxygen nucleophiles such as alkoxides, sodium azide, hydrazine, sulfur containing nucleophiles, cyanide, etc., and reactions of this type are typical of the group (see Chapter 2.02). 

Oxygen nucleophiles may also add to cyano groups, in many instances providing entry into the isoxazole system (Chapter 4.16). These reactions are illustrated by the conversion of the 2-arylhydrazono-3-oxonitrile (325) into a 5-aminoisoxazole (327). Treatment of... 

Acids are poor catalysts for ring cleavage of thiirane 1,1-dioxides but are good catalysts for reactions of thiirane 1-oxides with nucleophiles. These reactions of episulfoxides are believed to proceed by protonation of the oxygen atom (but see the NMR evidence cited above for 5-protonation in fluorosulfonic acid) and will be treated in the section on nucleophilic reactions. 

These Br nsted-type plots often seem to be scatter diagrams until the points are collated into groups related by specific structural features. Thus, p-nitrophenyl acetate gives four separate, but parallel, lines for reactions with pyridines, anilines, imidazoles, and oxygen nucleophiles.Figure 7-4 shows such a plot for the reaction of trans-cmmm c anhydride with primary and secondary aliphatic amines to give substituted cinnamamides.All of the primary amines without substituents on the a carbon (R-CHi-NHi) fall on a line of slope 0.62 cyclopentylamine also lies on this line. If this line is characteristic of normal behavior, most of the deviations become qualitatively explicable. The line drawn through the secondary amines (slope 1.98) connects amines with the structure R-CHi-NH-CHi-R. The different steric requirements in the acylation reaction and in the model process... 

Figure 7-5. Bry4nsted-type plot for nucleophilic reactions of p-nitrophenyl acetate. Key , simple imidazoles in 28.5 ethanol at JO°C. p = 0.80 (data from Ref. 197] O, oxygen anions, in water at 25°, P = 0.95 for linear portion [data from Ref. 119, 198] O, a effect nucleophiles. Several of the nucleophiles are identified.

Discuss possible reasons for the curvature in the Br nsted-type plot of Fig. 7.5 for the nucleophilic reactions of oxygen nucleophiles. 

The reactions shown above are nucleophilic substitutions that involve replacement of bromine by oxygen. The reactions may or may not proceed by similar mechanisms. 

The Michael aclcliQon of oxygen-nucleophiles followed by subsequent cyclizadon or cycloaddidon provides an important method for the preparadon of oxygen-heterocycles such as tetrahydrofurans For example, 3-nitro-2//-chromenes bearing various snbsdtnents are prepared by the reaction of snbsdtnted sahcylaldehydes with nitro ilkenes fEq 4 14 ... 

Scheme 2.37 Intramolecular reaction of an oxygen nucleophile to give dihydrofurans.

Finally, an intramolecular reaction of an oxygen nucleophile to give 2,5-dihy-drofuran derivatives 146 is shown in Scheme 2.37. Since the vinylaziridines were generated in situ by treatment of imines 143 with ylide 144, this ylide is formally acting as an equivalent of the 2,5-dihydrofuran anion [57]. 

With Oxygen Nucleophiles Aziridine ring-opening of 111 (Scheme 3.42) with water in the presence of a catalytic amount of TsOH gave the corresponding (3-hydrox-yphenylalanine derivative 121 in 72% yield as the major isomer [74], Treatment of N-(p-tolylsulfmyl) aziridine-2-carboxylates with TFA and subsequent aqueous workup resulted in the formation of j3-substituted serine derivatives [62, 63, 101]. Under these reaction conditions, not only was the aziridine ring opened, but also the N-sulfmyl group was removed treatment of 122 (Scheme 3.43) with TFA at 73 °C, for example, afforded 123 in 75% yield [101],... 

The regioselective ring-opening of vinyloxiranes by nitrogen nucleophiles offers an attractive route to vie-amino alcohols, compounds of much recent interest. As with oxygen nucleophiles, the stereochemistry of the reaction can be controlled by choice of reaction conditions aminolysis of 25, for example, affords anti-amino alcohol 26 in excellent yield and diastereoselectivity (Scheme 9.21) [48, 96, 97], and... 

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