Thionyl chloride with oximes

Butler, R. N., O Donoghue, D. A. Direct detection of intermediates and synthetic applications of the reaction of thionyl chloride with oximes of substituted acetophenones and benzaldehydes Beckmann rearrangements. J. Chem. Res., Synop. 1983,18-19. 

The oxime of l-methyl-4-phenyl-4-benzoylpiperidine (25) was found to decompose by the action of thionyl chloride with formation of l-methyl-4-phenyl-3-piperideine and benzonitrile.19... 

Toluenesulfonic anhydride has been prepared from the acid by the use of thionyl chloride and phosphorus pentoxide. It has also been obtained by heating oxime -toluenesulfonates, by reaction of -toluenesulfonic acid with di- -tolylcarbodiimide, and by the interaction of methoxyacetylene and -toluenesul-fonic acid. ... 

Further, d-citronellal, the corresponding aldehyde, may be converted into citronellic acid through its oxime and nitrile. Citronellic acid, when treated with thionyl chloride in benzene solution, yields a chloride of a chlorinated acid which is converted by the action of alcohol into the hydrochloride of ethyl citronellate, or hydrochloride of ethyl rhodinate,... 

Beckmann rearrangement of benzophenone oxime to benz-anilide. Dissolve 2 g. of benzophenone oxime in 20 ml. of anhydrous ether in a small conical flask and add 3 g. of powdered phosphorus pentachloride (or 3 ml. of pme thionyl chloride). Distil off the solvent and other volatile products on a water bath CAUTION ether), add 25 ml. of water, boil for several minutes and break up any lumps which may be formed. Decant the supernatant liquid, and recrystallise, in the same vessel, from boiling alcohol. The product is benzanilide, m.p. 163° confirm this by a mixed m.p. determination with an authentic specimen. 

The natural antipode of corynantheine (35, 155, 20/ ) has elegantly been prepared by Autrey and Scullard (168), starting from yohimbone (305), synthesized and resolved previously by Swan (169). Yohimbone (305) was converted to 18-formylyohimbone (306) and then through 307 to oxime 308. On reaction with thionyl chloride, 308 underwent a Beckmann fragmentation to the trans-substituted indolo[2,3-a]quinolizine 310, which after desulfurization and esterification resulted in the levorotatory methyl corynantheate (304). This product... 

Several steroidal cyclobntanone oximes were nsed to investigate the rearrangement reaction. The oxime 338, treated with thionyl chloride in benzene solution at room temperature, gave the expected pyrrolidinone 339 in 71% isolated yield (equation 127). 

The incorporation of complex side chains at the 7 position based on alkyloximes of 2-amino-thiazole-5-gyloxylamides has provided drugs with very wide antibacterial activity that extend to hitherto resistant species such as pseudomonas. The preparation of one of the simpler side chains involves, first, the formation of the methyl ether from the oxime obtained by the nitrosation of methyl acetoacetate. Chlorination of the product, for example with sulfuryl chloride, gives the intermediate (21-1). The aminothiazole ring is then formed by reaction of that with thiourea to give (21-2). The free acid (21-3) is obtained by saponification of the product. The protected acid chloride (21-5) is obtained by sequential acylation of the amino group with chloroacetyl chloride and then reaction with thionyl chloride. 

During an elegant synthesis of biotin the oxime 1 was treated with thionyl chloride at 0°C in the expectation that Beckmann rearrangement would occur. The product, however, was found to be 2(75%). 

Treatment of oxime 60 with thionyl chloride/diisopropylethylamine produced, initially, cyclic sulfite 61 (Equation 11) <2005JOC8560>. 

The reaction of methyl (3-hydroxypyridin-2-yl)ketone oxime (487) with thionyl chloride, trichloroacetyl isocyanate or chlorosulfonyl isocyanate gave 3-methylisoxazolo[4,5-6]pyridine (488) in varying yields dependent upon the temperature and solvent (Equation (43)) <87H(26)292l>. Trichloroacetyl isocyanate was particularly effective in the formation of compound (488) in either diethyl ether or tetrahydrofuran, at ambient temperature or at reflux, affording 60-78% yields. The treatment of 2-acetyl-3-hydroxypyridine (489) with hydroxyamine 0-sulfonic acid afforded a 1 1 mixture of compound (488) and 2-methyloxazolo[4,5-6]pyridine (490) (Equation (44)). The formation of the isomer (490) results from a Beckmann rearrangement. 

Strychnine condenses with amyl nitrite in the presence of sodium ethoxide to give 11-oximinostrychnine (LI) (67, 68). This oxime undergoes Beckmann rearrangement with thionyl chloride to give two products, LII and LIII, the first of which gives the amino acid LIV on... 

Beckmann rearrangement of 2,2,6,6-tetramethyl-4-piperidone oxime with thionyl chloride followed by oxidation gave the stable free radical 159.167 Beckmann rearrangement of the N-oxide radical of the piperidone oxime gave the same free radical (159).168... 

In strong acids, or when treated with reagents such as thionyl chloride or phosphorus pentachloride, an oxime will react to give a rearranged amide. This is known as the Beckmann rearrangement. When the reaction gives products other than amides, these products are referred to as abnormal products. One such abnormal pathway is illustrated in Problem 4.14. 

A second partial synthesis of mexicanolide (69) from 7-deacetoxy-7-oxo-khivorin (70) has been reported (see Vol. 1, p. 183). This differed only in the method used to cleave ring B. The oxime (71) underwent a Beckmann rearrangement with thionyl chloride to give the lactam (72) which was converted into the... 

The dioxime of a cyclic 1,2-diketone (prepared in this example by successive nitrosation and oximation of the 1,3-cyclohexanedione) is oxidized to a furoxan (l,2,S-oxadiazole 2-oxide) the isomeric N-oxide is formed by mild treatment of the dioxime with thionyl chloride [2496]. 

Boiling the oxime (95.4) with thionyl chloride in benzene converts it into a fused oxathiadiazole in high yield. 

By treatment of this oxime with phosphorus pentachloride or thionyl chloride in ether solution, smooth conversion into benzanilide, m.p. 163°, results. The change of any oxime into a substituted amide under the conditions mentioned is usually termed the Beckmann rearrangement. The above example may be represented ... 

The side chain is prepared by the interaction between either ethylene oxide or l-chloro-2-hydroxy ethane with diethyl amine in methanol yields 2-hydroxy-triethyl hydrochloride. This on chlorination with thionyl chloride yields 2-chloro-triethyl amine whieh on treatment with ethyl aceto-acetate in the presence of sodium ethoxide gives an intermediate eompound. Alkaline hydrolysis produces l-acetyl-3-diethylamino propane which on reduction with Raney Nickel followed by oximation yields 4-amino-1-diethylamino pentane. 

The fused cyclobutane derivatives produced via the above cycloaddition reactions have been utilized as synthetic precursors for the preparation of indole-2-acetonitriles (Scheme 6) [23]. First, the acetyl-substituted cyclobutanes 28 were converted to the cyclobutanone derivatives 29, which were in turn treated with hydroxylamine to provide the corresponding oximes. Beckmann fission of oximes 30 in the presence of thionyl chloride then produced the l-benzoylindole-2-aceto-nitrile derivatives 31 in good yield. 

The parent compound of this series, 2-chloro-3,4,5,6-tetrahydro-pyridine (XXXIX), was obtained as an intermediate in the Beckmann rearrangement of cyclopentanone oxime ( ). Thus, heating of cyclo-pentanone oxime with thionyl chloride affords about equal amounts of the lactam hydrochloride XL and the imidoyl chloride XXXIX ( ). 

Eligh yields of esters are obtained from both acid-sensitive (cyanoacetic acid) and base-sensitive carboxylic acids (3-phenyl-propionic acid and trichloroacetic acid) and, in these latter cases, use of 4-(dimethylamino)pyridinium chlorosulfite chloride is much more effective than use of thionyl chloride alone. The esterification process has been claimed to be independent of the steric environment of the carboxyl function, though this reagent may be of more limited value with heavily substituted benzoic acids. Carboxyl activation, in the presence of a primary amine, leads to the corresponding amide in excellent yield (eq 2). In both the esterification and amidation processes and the oxime dehydration reaction discussed below, recovery of DMAP is straightforward. 

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