Oximino Compounds

The yield of 18-oximino compounds from 20jS-nitrites varies from 15 to 36% whereas with a 20oc-nitrite a 60-65% yield is reported. This difference has been ascribed to steric hindrance in the transition state for hydrogen abstraction in the case of the 20j3 derivative. Similar differences... 

Scheme 21 summarizes further reactions leading to phosphonic acid analogues of amino acids. Treatment of the nitrone (138 R =Me or Pr ) with a dialkyl hydrogen phosphonate (best as the Li derivative which shows greater diastereoselectivity than the Na or K salts), and subsequent steps involving acidolysis of the oximino compound (139) lead to the free (ot-aminoalkyl)-phosphonic acids (140)(phosphonoalanine, phosphonova1ine). 

Wittig-Horner reaction (see p. 241). Photolysis of the nitrite of the 21-chloro-20-hydroxy-compound (194) gave the 18-oximino-compound (195) which on Jones oxidation was converted into the chlorolactone (196). Hypoiodite reaction of the 21-chloro-20-hydroxy-compound (194) also gives the chloro-lactone (196) which with modification gives 18-hydroxy-11-deoxycorticosterone (see also ref. 198). 

An example of the Knorr pyrrole synthesis is provided by the formation of 3,5-diethoxycarbonyl-2,4-dimethylpyrrole (55). Overall ring construction in this case may be related to (46) above. A retrosynthetic analysis involving disconnection of the N—C2 bond, appropriate prototropic shifts, and finally a retro-aldol reaction to effect disconnection of the C3—C4 bond, reveals ethyl acetoacetate and ethyl a-aminoacetoacetate (ethyl 2-amino-3-oxo-butanoate) (56) as reagents. An FGI transform on this latter compound generates the corresponding nitroso (oximino) compound which may also be derived from ethyl acetoacetate. 

In practice the synthesis (Expt 8.16) is a one-pot reaction in which one-half of the ethyl acetoacetate is converted to the oximino compound by treatment with... 

Animals. Hydrolyzed to an oximino metabolite (methyl N-hydroxy-/v",iV -dimethyl-1 -thiooxamimidate) or converted enzymically via W,W-dimethyl-1 -cyanoformamide to N,N-dimethyloxamic acid. Conjugates of the oximino compound, the acid, and their monomethyl derivatives constituted over 70% of thermetabolites excreted in the urine and feces... 

Plants. Hydrolyzes to the corresponding oximino compound which, in turn, conjugates with glucose. Total breakdown into natural products has been demonstrated... 

Aminomalononitrile (readily made in 45-50% yield by reduction of the oximino compound with aluminium amalgam) condenses with formamidine acetate in ethanol to give 5-amino-4-cyanoimidazole in 35% yield [34]. 

The standard /3-ketoester-hydrazine reaction for preparation of 2-pyrazolin-5-ones has been used for direct synthesis of the 4-oximino derivatives by starting with an a-oximino-jS-ketoester.269,1125,1534,1536 In a modification of this by Biilow and Bozenhardt258 a hydrazone of the a-oximino-j8-ketoester was used. Ponzio and Ruggeri1125 have used a-oximino-j8-hydrazonohydroxamic acids and hydrazines, and other oximino compounds, as illustrated in eq. 209. 

These compounds are listed in Table XLVIII. 4-Amino-3,5-pyrazolidinediones have been prepared by reduction of the corresponding 4-oximino compounds.981 1048,1339 The preparation of 4-arylazo-3,5-pyrazolidinediones by direct introduction of this substituent has already been mentioned in Section 2 of this chapter.976,1048 Billow and Bozenhardt257 have prepared 4-phenylazo-3,5-pyrazolidinedione by cyclization of the phenylhydrazone of mesoxalic acid hydrazide in acetic acid (eq. 259). Stepanov and Kuzin1340 have suggested that the... 

XIII). A thermal retro-Diels-Alder reaction of 39 liberating cyclopen-tadiene was used to afford a diene oxime ether which cyclized to give a tetracyclic indole as a 3 2 mixture of diastereomers. Three additional steps served to convert this adduct to ( )-lysergic acid (40). Of particular interest here is the fact that simple oximino compounds are not normally reactive dienophiles, and the intramolecularity of the conversion is apparently crucial to the success of this transformation. 

Miscellaneous Rearrangements.—An improved non-photochemical route to 13-epi-androstanes and -oestranes involved conversion of the appropriate 17-oximino-compounds with boiling acetic anhydride-pyridine into the enamide (176) and the enimide (177) which were readily hydrolysed to the 17-oxo-... 

The 2)5-hydroxy-3-oximino-compound (379) suffers Beckmann fragmentation with thionyl chloride to give the cyanoaldehyde (380), offering a controlled method for unsymmetrical cleavage of the ring. ... 

An indirect synthesis " of eburnamonine (vincamone) results from the ring contraction of (-)-homovincamone (210) by Beckmann rearrangement of the derived a-oximino-compound, since (210) has previously been obtained by partial synthesis from (—)-vincadiflEormine. The initial product of the... 

It is assumed that hydroxylamine condenses with chloral to give oxime, which then undergoes the nucleophilic substitution with aniline, and hydrolyzes to give oximino intermediate under basic conditions. In the presence of a strong acid, such as concentrated sulfuric acid, the oximino compound cyclizes via nucleophilic addition of aromatic ring to C=N double bond. An illustrative mechanism is provided below. 

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