Bromine oxidation, diols

Several new procedures for the selective oxidation of secondary alcohols in the presence of primary alcohols have appeared. Distannoxane-bromine, a neutral reagent, efficiently oxidizes secondary or benzylic alcohols to ketones in the presence of primary alochols.62 Trialkyltin alkoxides and bromine oxidize both primary and secondary alcohols.63 Woelm W-200, neutral, dehydrated alumina oxidizes secondary alcohols to ketones in the presence of primary alcohols with trichloroacetaldehyde as the hydride acceptor.6 The reverse reduction process had previously been reported. Oxidation of triphenylmethyl ethers of primary, secondary diols with triphenyl carbenium salts proceeds only at the secondary positions.65... 

The bromine linked to a double bond or linked to an aromatic nucleus are much more stable structures (not easily decomposed to HBr as dibromo neopentylglycol, a saturated aliphatic bromine compound). Thus, a very successful bromine containing diol, produced industrially [4, 24], is based on tetrabromophthalic anhydride. Tetrabromophthalic anhydride is reacted first with diethylene glycol and the resulting half ester is reacted with propylene oxide (PO) (reaction 18.5) [3]. 

The synthesis of sixteen methyl D-hexopyranosid-2-, 3-, or 4-ulosides by bis(tributyltin)-oxide - bromine oxidation of unprotected methyl glycosides has been described. Axial hydroxy groups in l,2-ci,s-diols are preferentially oxidised by this system. The stmctures of some of the products were confirmed by independent syntheses involving oxidation of partially protected derivatives. In related work some carbohydrate 1,2-diol dibutylstannylene acetals have been regiospecifically oxidized by NBS (rather than bromine) to give a-hydroxyketones. A Sn n.m.r. study on the stannylene acetals has shown some of them to be dimers. ... 

Addition of halogens proceeds stepwise, sometimes accompanied by oxidation. Iodine forms 2,3-diiodo-2-butene-l,4-diol (53). Depending on conditions, bromine gives 2,3-dibromo-2-butene-l,4-diol, 2,2,3,3-tetrabromobutane-l,4-diol, mucobromic acid, or... 

Analysis. Butenes are best characterized by their property of decolorizing both a solution of bromine in carbon tetrachloride and a cold, dilute, neutral permanganate solution (the Baeyer test). A solution of bromine in carbon tetrachloride is red the dihaUde, like the butenes, are colorless. Decoloration of the bromine solution is rapid. In the Baeyer test, a purple color is replaced by brown manganese oxide (a precipitate) and a colorless diol. These tests apply to all alkenes. 

Mechanisms involving glycol bond fission have been proposed for the oxidation of vicinal diols, and hydride transfer for other diols in the oxidation of diols by bromine in acid solution.The kinetics of oxidation of some five-ring heterocyclic aldehydes by acidic bromate have been studied. The reaction of phenothiazin-5-ium 3-amino-7-dimethylamino-2-methyl chloride (toluidine blue) with acidic bromate has been studied. Kinetic studies revealed an initial induction period before the rapid consumption of substrate and this is accounted for by a mechanism in which bromide ion is converted into the active bromate and hyperbromous acid during induction and the substrate is converted into the demethylated sulfoxide. 

Oxidation and Reduction.—A number of selective oxidation procedures have been reported. Trichloroacetaldehyde on dehydrated chromatographic alumina converts the diol (15) into the 3/3-hydroxy-17-ketone (68%)." Primary alcohols are reported to be less readily oxidized than secondary alcohols by this reagent. Similarly, bromine or chlorine with HMPA oxidizes secondary alcohols more readily than primary alcohols. Thus the diol (16) was converted into the ketol (17)... 

Regioselective oxidation of 1,2-diols.1 The oxidation of di-secondary glycols to acyloins (5, 188) can be extended to oxidation of other glycols. Thus the stan-nylene of 1 is oxidized by bromine to 2 in high yield. The reaction is regioselective with unsymmetrical diols (3 — 4). 

The selective oxidation of the secondary alcohol is performed by dropping a bromine solution on a mixture of (Bu3Sn)20 and the diol in CH2CI2. Although, no complete formation of bis-tin alkoxide is secured and the generated HBr—that may cause the hydrolysis of tin alkoxides—is not quenched, a useful yield of hydroxyketone is obtained. 

Zinc serves to further reduce osmium and free the diol product. Similar oxidative additions to alkenes occur with bromine, chlorine, IN3, peracids, and many other electrophiles. 

Selective oxidations with bromine. Bromine in combination with this Ni(II) alkanoate promotes the selective oxidation of primary, secondary 1,4-diols to y-butyrolactones (equation I).1... 

A new ionic liquid, l-butyl-3-methylimidazolium tribromide can act as an oxidizing agent to convert alcohols to aldehydes and ketones.338 In the case of benzyl alcohols and diols, [Bmim][Br3] combines oxidizing and brominating properties in a one-pot synthesis of /3-bromoethyl esters. 

Bromine in an alcohol can be used for the direct conversion of an aldehyde into an ester, as with 46.152 The aldehyde 45 can be generated in situ by Swern oxidation of an alcohol or, as in the case of the diol 39, by periodate cleavage.153... 

A modification of GSR has been reported by Classon and co-workers.190 The idea remains the same create a covalently bound phosphorus cation and displace with a nucleophile—in this case, a halogen. Both bromine and iodine have been used.190 Three different systems were evaluated (1) chlorodiphenylphophine, iodine-bromine, and imidazole (2) p-(dimethylamino)phenyldiphenylphosphine, iodine-bromine, and imidazole or (3) polymer-bound triphenylphosphine, iodine-bromine, and imidazole. The last two were found to be very similar to just triphenylphosphine itself, and displayed reactivity inferior to the first system. The polymer-bound reagent does allow for easier removal of triphenylphosphine oxide produced in the course of the reaction. As with the original procedure, and consistent with a Sn2 mechanism, inversion of configuration occurred. Again, as with the original method vicinal diols were readily converted into alkenes.191 This... 

Most butynediol produced is consumed in the manufacture of butane-diol and butenediol. Butynediol is also used for conversion to ethers with ethylene oxide and in the manufacture of brominated derivatives that are useful as flame retardants. Butynediol was formerly used in a wild oat herbicide, Carbyne (Barban), 4-chloro-2-butynyl-A-(3-chlorophenyl)carba-mate (CnH9Cl2N02). 

There is one report on the synthesis of several pentacoordinate 1,2A4- and l,2A6-oxathietanes, which is outside the categories discussed above <1996JA697, 1996JA12455>. Treatment of diols 61a or 61b with bromine under basic conditions leads to the formation of pentacoordinate l,2A4-oxathietanes 62a and 62b in 8% and 62% yields, respectively (Scheme 17). Oxidation of these substrates furnishes the observed pentacoordinate l,2A6-oxathietanes 63a and 63b in poor yield. 

An improved route to 2a-hydroxycholesterol has been devised as part of the preparation of 2a-hydroxy-vitamin D3 (263 R1 = R4 = R5 = R6 = H, R2 = R3 = OH).123 Hydroxylation of the A bond of cholesta-l,5-dien-3/3-ol by means of 9-borabicyclo[3,3,l]nonane followed by reaction with alkaline hydrogen peroxide produced the 2-equatorial 2a,3a-diol in 70—80% yield. The conventional four-step sequence, acetylation, bromination, dehydrobromination, and hydrolysis, gave 2a -hydroxycholesta-5,7-dien-3/3-ol which was converted into 2a-hydroxy-vitamin D3. The isomeric 2/3-hydroxy-vitamin D3 has also been reported.124 Reaction of the 1/6,2/3-oxide obtained by peroxidation of the adduct (265) with lithium aluminium hydride results in a mixture of 2/3,3/3-dihydroxycholest-5,7-diene and its 1/3,3/3-dihydroxy-epimer in the ratio 8 1. Irradiation of the former 5,7-diene furnished the expected previtamin, which on equilibration gave 2/3-hydroxy-vitamin D3 (263 R1 = R4 = R5 = R6 = H, R2 = a-OH, R3 = OH). 

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