Pyridine chromium

B. General Oxidation Procedure for Alcohols. A sufficient quantity of a 5% solution of dipyridine chromium (VI) oxide (Note 1) in anhydrous dichloromethane (Note 7) is prepared to provide a sixfold molar ratio of complex to alcohol. This excess is usually required for complete oxidation to the aldehyde. The freshly prepared, pure complex dissolves completely in dichloromethane at 25° at 5% concentration to give a deep red solution, but solutions usually contain small amounts of brown, insoluble material when prepared from crude complex (Note 8). The alcohol, either pure or as a solution in anhydrous methylene chloride, is added to the red solution in one portion with stirring at room temperature or lower. The oxidation of unhindered primary (and secondary) alcohols proceeds to completion within 5 minutes to 15 minutes at 25° with deposition of brownish-black, polymeric, reduced chromium-pyridine products (Note 9). When deposition of reduced chromium compounds is complete (monitoring the reaction by gas chromatography or thin-layer chromatography analysis is helpful), the supernatant liquid is decanted from the (usually tarry) precipitate and the precipitate is rinsed thoroughly with dichloromethane (Note 10). 

Evans GW, Pouchnik DJ. 1993. Composition and biological activity of chromium-pyridine carboxylate complexes. J Inorg Biochem 49 177-187. 

A triple bond activates the adjoining methylene group for oxidation to a carbonyl group. Thus 5-decyne furnishes a 46% yield of 5-decyn-4-one on treatment with chromium-pyridine in dichloromethane for 24 h at room temperature [601]. 

We shall describe a specific synthetic example for each protective group given above. Regiosdective proteaion is generally only possible if there are hydroxyl groups of different sterical hindrance (prim < sec < tert equatorial < axial). Acetylation has usually been effected with acetic anhydride. The acetylation of less reactive hydroxyl groups is catalyzed by DMAP (see p.l44f.). Acetates are stable toward oxidation with chromium trioxide in pyridine and have been used, for example, for protection of steroids (H.J.E. Loewenthal, 1959), carbohydrates (M.L. Wolfrom, 1963 J.M. Williams, 1967), and nucleosides (A.M. Micbelson, 1963). The most common deacetylation procedures are ammonolysis with NH in CH OH and methanolysis with KjCO, or sodium methoxide. 

Pyridine Chlorosulfonic acid, chromium trioxide, formamide, maleic anhydride, nitric acid, oleum, perchromates, silver perchlorate, sulfuric acid... 

The formation of an epoxyketone (1) is generally favoured when the expected product of oxidation of an allylic alcohol is a cisoid enone. This type of reaction is promoted by acid conditions and may be prevented by using the chromium trioxide-pyridine reagent which gives only the unsaturated ketone (2) corresponding to the starting alcohol. ... 

If homolytic reaction conditions (heat and nonpolar solvents) can be avoided and if the reaction is conducted in the presence of a weak base, lead tetraacetate is an efficient oxidant for the conversion of primary and secondary alcohols to aldehydes and ketones. The yield of product is in many cases better than that obtained by oxidation with chromium trioxide. The reaction in pyridine is moderately slow the intial red pyridine complex turns to a yellow solution as the reaction progresses, the color change thus serving as an indicator. The method is surprisingly mild and free of side reactions. Thus 17a-ethinyl-17jS-hydroxy steroids are not attacked and 5a-hydroxy-3-ket-ones are not dehydrated. 

Oxidation of carbinols with chromium tri-oxide-pyridine... 

In a typical Knof procedure, 3jS-hydroxyandrost-5-en-17-one acetate is epoxidized with perbenzoic acid (or m-chloroperbenzoic acid ) to a mixture of 5a,6a- and 5)5,6)5-epoxides (75) in 99 % yield. Subsequent oxidation with aqueous chromium trioxide in methyl ethyl ketone affords the 5a-hydroxy-6-ketone (76) in 89% yield. Baeyer-Villiger oxidation of the hydroxy ketone (76) with perbenzoic acid (or w-chloroperbenzoic acid ) gives keto acid (77) in 96% yield as a complex with benzoic acid. The benzoic acid can be removed by sublimation or, more conveniently, by treating the complex with benzoyl chloride and pyridine to give the easily isolated )5-lactone (70) in 40% yield. As described in section III-A, pyrolysis of j5-lactone (70) affords A -B-norsteroid (71). Knof used this reaction sequence to prepare 3)5-hydroxy-B-norandrost-5-en-17-one acetate, B-noran-... 

The intermediacy of dipolar species such as 186 has been demonstrated by reaction of enamines with 2-hydroxy-1-aldehydes of the aromatic series (129). The enamine (113) reacts in benzene solution at room temperature with 2-hydroxy-1-naphthaldehyde to give the crystalline adduct (188) in 91 % yield. Oxidation with chromium trioxide-pyridine of 188 gave 189 with p elimination of the morpholine moiety. Palladium on charcoal dehydrogenation of 189 gave the known 1,2-benzoxanthone (129). 

Figure 14.17 Structures of (a) the tetraperoxochromate(V) ion [Cr (02)4] , (b) the pyridine oxodiperoxo-chromium(VI) complex [Cr 0(02)2py], and (c) the triamminodiperoxochromium(IV) complex [Cr" (NH3)3(02)2] showing important interatomic distances and angles. (This last compound was originally described as a chromium(II) superoxo complex [Ci (NH3)3(02)2] on the basis of an apparent 0-0 distance of 131 pm/ and is a salutary example of the factual and interpretative errors that can arise even in X-ray diffraction studies. " ...

The immediate outcome of the Hantzsch synthesis is the dihydropyridine which requires a subsequent oxidation step to generate the pyridine core. Classically, this has been accomplished with nitric acid. Alternative reagents include oxygen, sodium nitrite, ferric nitrate/cupric nitrate, bromine/sodium acetate, chromium trioxide, sulfur, potassium permanganate, chloranil, DDQ, Pd/C and DBU. More recently, ceric ammonium nitrate (CAN) has been found to be an efficient reagent to carry out this transformation. When 100 was treated with 2 equivalents of CAN in aqueous acetone, the reaction to 101 was complete in 10 minutes at room temperature and in excellent yield. 

A recently discovered (2) oxidizing system promises to become very important for the oxidation of acid-sensitive compounds. The reagent is chromium trioxide-pyridine complex, which may be isolated after preparation and employed in nonaqueous solvents (usually methylene chloride). A remarkable feature of the reagent is that good yields of aldehydes are obtained by direct oxidation of primary alcohols. The preparation of the reagent and its use are given. 

A 1-liter flask is equipped with a magnetic stirrer, a thermometer immersed in the reaction mixture, and a drying tube. In the flask is placed 100 ml of anhydrous pyridine, and the flask is cooled in an ice-water bath to 15-20° (lower temperatures impede the complex formation). Chromium trioxide (80 g) is added in small portions to the stirred solvent at a rate so as to keep the temperature below 30°. After about one-third of the chromium trioxide has been added, the yellow complex begins to precipitate. At the end of the addition (about 1 hour), a slurry of the yellow complex in pyridine remains. (This form of the complex is apparently a microcrystalline form and is very difficult to handle.)... 

D. Oxidation with Chromium Trioxide-Pyridine Complex General Procedure... 

A 5% solution of chromium trioxide-pyridine complex in dry methylene chloride is prepared. The alcohol (0.01 mole) is dissolved in dry methylene chloride and is added in one portion to the magnetically stirred oxidizing solution (310 ml, a 6 1 mole ratio) at room temperature. The oxidation is complete in 5-15 minutes as indicated by the precipitation of the brownish black chromium reduction products. The mixture is filtered and the solvent is removed (rotary evaporator) leaving the crude product, which may be purified by distillation or recrystallization. Examples are given in Table 1.1. 

Chromium trioxide-pyridine complex (Chapter 1, Section I) EK... 

---