Daniel Swern

Oxidation of alcohols by “activated” dimethyl sulfoxide. a preparative, steric and mechanistic study

Abstract The oxidation of primary, secondary, allylic, benzylic, hindered and bicyclic alcohols with dimethyl sulfoxide (DMSO) “activated” by numerous electrophiles was studied: yields of carbonyls, by-products and recovered alcohols were quantitatively determined. Pathways for carbonyl and by-product formation are presented. Generally, yields of carbonyls increase with increased steric hindrance in the alcohols. Steric effects of tertiary amines, used for basification, were also investigated, and the results are consistent with the suggested reaction pathways. Among previously unreported “activators,” oxalyl chloride is the most generally effective; yields of carbonyls are typically over 95%. Thionyl chloride is also a satisfactory “activator” although yields of carbonyls are not quite as high. An improved method of preparation of alkyl methylthiomethyl ethers, by-products of the oxidation process, is reported.

Dehydroepiandrosterone: An anti‐obesity and anti‐carcinogenic agent

Long-term treatment of female C3H-Avy/A (obese) and C3H-A/A (non-obese) mice with dehydroepiandrosterone, an adrenal steroid found in subnormal levels in women predisposed to develop breast cancer, reduces weight gain without suppressing appetite and significantly inhibits the development of spontaneous breast cancer. This steroid also antagonizes the capacity of the tumor promoter, 12-0-tetradecanoyl-phorbol-13-acetate, to stimulate 3H-thymidine incorporation in mouse epidermis and in a cultured rat kidney epithelial cell line.

Application of urea complexes in the purification of fatty acids, esters, and alcohols. III. Concentrates of natural linoleic and linolenic acids

SummaryConcentrates of natural linoleic acid (linoleic acid content, 85–95%) have been prepared in 50–72% yields from corn oil fatty acids by preferential precipitation of the saturated and monounsaturated fatty acids at room temperature as their urea complexes.By a similar procedure, concentrates of natural linolenic acid (linolenic acid content, 87–89%) have been prepared in 55–61% yields from perilla oil fatty acids by preferential precipitation of the saturated, monounsaturated, and diunsaturated fatty acids. Although concentrates of natural linolenic acid containing only 66–70% linolenic acid were obtained from linseed oil fatty acids, yields were 87–90%.A levelling-off effect has been observed in the use of the preferential precipitation technique in raising the purity of concentrates of linoleic and linolenic acid. This parallels the experience in the purification of these acids by low-temperature crystallization.

Biological effects of the polymeric residues isolated from autoxidized fats

SummaryThere is increasing evidence that the abnormal nutritional properties of highly autoxidized fats are related to the polymers which develop during autoxidation. Lard and cottonseed oil were aerated at 95°C. for 200 hrs. and molecularly distilled; and the residue fractions, non-volatile at 275 to 300°C., were studied.Diets containing 20% of autoxidatively produced polymeric residue, fed to albino rats, led to diarrhea and rapid death, but when this residue was reduced to 10%, most of the animals were gradually able to tolerate it. At the 4 or 7% level it was well tolerated, but growth was reduced. There were no distinctive histological lesions, and withdrawal of the polymer permitted immediate realimentation without evidence of subsequent injuries.The polymeric residue from autoxidized cottonseed oil exerted a greater growth-depressant effect than that from lard, and the latter, more than that from a hydrogenated vegetable oil used for deep-fat frying for 80 hrs. at 190°C. Addition of fresh fat to the polymeric residues decreased their growth-depressant effect.When rats were fed a measured amount of diet sufficient to maintain their weight, the caloric requirement necessary for weight maintenance gradually decreased. When the dietary fat source consisted of polymeric residue to the extent of 4 to 10%, the caloric requirement for weight maintenance decreased relatively little, if at all. The polymeric residue from autoxidized lard was, in this respect, as effective as that from autoxidized cottonseed oil.

Reactions of fatty materials with oxygen. IV.1 Quantitative determination of functional groups

SummaryConventional analytical procedures employed in oxidation reactions for the quantitative determination of functional groups have been applied to a series of pure compounds as well as to two synthetic mixtures and to methyl oleate hydroperoxide (estimated purity, 70%). In the absence of peroxide and oxirane groups the analytical procedures are reliable. When peroxides are present, unusually high and variable values for carbonyl oxygen are obtained, and the iodine and saponification numbers are generally unreliable. Determination of hydroxyl oxygen is interfered with by large proportions of oxirane compounds but apparently not by peroxides. Determination of acid number and peroxide and oxirane oxygen is reliable in the presence of all the other functional groups investigated. Techniques for the accurate determination of functional groups when peroxide and oxirane groups are present are described.A modified procedure for the determination of carbonyl oxygen is reported.

Purification of oleic acid, methyl oleate, and oleyl alcohol for use as chemical intermediates

Summary1. Oleic acid, methyl oleate, and oleyl alcohol of high purity (93 to 96%) were prepared from readily available and inexpensive commercial materials in 65 to 70% yields by fractional distillation and a single low-temperature fractional crystallization.2. In the fractional distillation of red oil and its methyl esters, lower fractions amounting to about 20% of the starting material were obtained. These are suggested for use in soap manufacture.3. A fraction containing more than 50% linoleic acid was obtained from the C-18 fraction of red oil by fractional crystallization. This fraction amounted to about 20% of the total starting material and had approximately the same percentage composition of fatty acids as several important semi-drying oils.

Reactions of fatty materials with oxygen. VIII. Cis-trans isomerization during autoxidation of methyl oleate

SummaryMethyl oleate irradiated with ultra-violet light has been autoxidized at 35° and the reaction has been followed by means of the infrared spectrophotometer. During the extremely early stages of autoxidation and continuing up to at least 700 hours, a cis-trans isomerization induced by oxygen is one of the reactions which occurs.The data suggest that most, if not all, of the peroxides produced during the autoxidation of methyl oleate, at least up to 300 hours, are trans peroxides and not methyl oleate peroxides, as had been previously supposed. A mechanism for the formation of trans peroxides from allylic free radicals is proposed.Mechanisms are also proposed for the formation of non-peroxidic trans materials during autoxidation. These could explain the formation of trans-9,10-epoxystearic acid and high melting 9,10-dihydroxystearic acid from autoxidizing oleic acid.

Application of urea complexes in the purification of fatty acids, esters, and alcohols. II. Oleic acid and methyl oleate from olive oil

SummaryOleic acid and methyl oleate of high purity (97–99%) and substantially free (0.2% or less) of polyunsaturated contaminants have been isolated in 60–70% yield from the fatty acids or methyl esters of olive oil by procedures which require only one precipitation of urea complexes (single dose of urea technique) one low-temperature crystallization, and one fractional distillation. The best yields of the highest purity acids are obtained when saturates are removed by fractional crystallization prior to a final distillation. The urea complex separation technique can be applied directly to olive oil methanolysis reaction mixtures without prior isolation of the mixed methyl esters.Oleic acid or methyl oleate obtained by decomposition of urea complexes contains approximately 1% of polyunsaturated contaminants. After fractional distillation or crystallization to separate saturated acids the oleic content is about 90–97%. Such products are satisfactory for many uses and in their preparation low-temperature (−50° or lower) crystallizations are not required.Solution and slurry techniques have been studied for the preparation of urea complexes from olive oil acids or esters. The former technique is preferred when a maximum of about 1,000 grams of acids or esters are to be processed. The latter is preferred for larger size experiments mainly because the volume of methanol employed is cut in half, the time is shorter, and also because yields are about 5% higher.

Mechanism of the reactions of oxygen with fatty materials. Advances from 1941 through 1946

SummaryA review of advances from 1941 through 1946 in the mechanism of the oxygen oxidation of fatty materials is given. Subjects discussed are the oxidation of monounsaturated compounds, nonconjugated and conjugated polyunsaturated compounds, and saturated compounds.The hydroperoxide theory of oxidation at active methylene groups is discussed in detail. There is good justification for postulating that autoxidative attack in olefins isinitiated universally by addition of oxygen at the double bonds in only afew of the molecules, and not by the formation of hydroperoxides. Subsequently, in the case of monoolefins and nonconjugated polyolefins, the attack by oxygen is continued bysubstitution on the α-methylene group to form hydroperoxides by means ofchain reactions. Mechanisms for such an oxidative scheme, involving the formation of intermediate free radicals, are given. In the case of conjugated compounds, peroxides are formed by addition of oxygen at the double bonds, and α-methylene group peroxidation does not occur. Although saturated compounds are relatively inert, they also form hydroperoxides, which are converted mainly to ketones and alcohols with the ketones predominating.The formation of polymers, which often account for the major proportion of the oxidation products of unsaturated compounds, also is discussed. The possibility of formation of carbon-to-carbon-linked as well as oxygen-linked polymers in the various classes of olefins is considered.

Application of urea complexes in the purification of fatty acids, esters, and alcohols. I. Oleic acid from inedible animal fats

SummaryUrea complex formation has been employed in the preparation of purified oleic acid (oleic acid content, 80–95%) from various grades of inedible animal fats and red oils. Since the urea complex of oleic acid forms in good yield at room temperature, low temperatures are not required in the isolation procedure. Yields of oleic acid are equal to or lower than those obtained by conventional low-temperature crystallization procedures, but the preparation of a polyunsaturate-free oleic acid is apparently not possible by urea complex formation alone. The separation of polyunsaturated acids from oleic acid by urea complex formation is more convenient than but not as efficient as by solvent crystallization, but separation of saturated acids from unsaturated acids is less convenient.Advantages and disadvantages in using urea in the preparation of purified oleic acid are briefly discussed.