78109-12-3Relevant articles and documents
Imino 1,2-Wittig rearrangement of hydroximates and its application to synthesis of cytoxazone
Miyata, Okiko,Koizumi, Tomoko,Asai, Hiroshi,Iba, Ryuichi,Naito, Takeaki
, p. 3893 - 3914 (2007/10/03)
The imino 1,2-Wittig rearrangement of hydroximates provides a novel method for the construction of 2-hydroxyoxime ethers. Upon treatment with LDA, Z-hydroximates smoothly underwent stereoselective rearrangement to give Z-2-hydroxyoxime ethers in good yield, which were converted into amino alcohols. On the other hand, the rearrangement of E-hydroximates gave a mixture of E- and Z-2-hydroxyoxime ethers. This method was successfully applied to a practical synthesis of cytoxazone.
Mechanisms of Alkoxide Substitution Reactions at the Carbon-Nitrogen Double Bond. Stereoelectronic Control during Nucleophilic Substitution
Johnson, James Elver,Nalley, Elizabeth Ann,Weidig, Charles,Arfan, Mohammed
, p. 3623 - 3629 (2007/10/02)
The stereochemistry and mechanisms of the alkoxide substitution reactions of O-methylbenzohydroximoyl chlorides (1 and 2) and alkyl O-methylbenzohydroximates (3 and 4) have been investigated.The reactions of the (Z)-hydroximoyl chlorides 1 with alkoxides in 10percent methanol-90percent Me2SO proceed with >= 95percent retention of configuration to give the (Z)-hydroximates 3.The alkoxide reactions of the (E)-hydroximoyl chlorides 2 are usually less stereospecific and give >= 77percent of the substitution product (4), corresponding to retention of configuration.The reactions of the hydroximoyl chlorides 1a and 2a with methoxide ion follow second-order kinetics and have approximately the same rate constants.The reaction of the hydroximoyl bromide 1h with methoxide is only 2.2 times faster than that of the chloride 1a.The methoxide substitution rates of five (Z)-hydroximoyl chlorides (1a, 1d-g) give a Hammett correlation with ? with a ρ value of 1.90.These observations are consistent with a mechanism in which a hydroximoyl chloride (1) undergoes rate-determining nucleophilic attack by methoxide to form a tetrahedral intermediate which rapidly loses chloride ion to give the hydroximate 3.The (Z)-hydroximate 3e undergoes a methoxide substitution reaction to give 4e but at a considerably slower rate than the (Z)-hydroximoyl chloride 1a (k(1a)/k(3e) = 53).The second-order rate constant for the reaction of the (Z)-hydroximate 3e with methoxide is about 300 times greater than the rate constant for the reaction of the (E)-hydroximate 4e with methoxide.The reaction of methoxide with the (E)-hydroximate 4e initially produces mainly the Z product 3a, but the product distribution changes with time, and eventually the E isomer 4a predominates.The change in product distribution during the course of this reaction is due to a methoxide-catalyzed isomerization of 3a to 4a.The stereochemistry and relative rates of the reactions of 1-4 with methoxide ion are interpreted in terms of Deslongchamp's theory of stereoelectronic control.It is suggested that stereoelectronically controlled loss of chloride ion from the tetrahedral intermediate 12 (from the reaction of 1a with methoxide ion) is faster than either loss of methoxide ion to give starting material or stereomutation.In the tetrahedral intermediate 13 (from 2a), stereomutation to 12 and 14 and stereoelectronically controlled loss of chloride ion from 12 and 14 are faster processes than loss of methoxide ion from 13.The tetrahedral intermediate 15 (from 3e) undergoes stereoelectronically controlled loss of methoxide or ethoxide ion faster than it undergoes stereomutation.In the case of the intermediate 17 (from 4e), stereoelectronically controlled loss of methoxide ion to give starting material is faster than stereomutation.
