Osmium tetroxide

Osmium tetroxide is one of the most efficient reagents for double bond dihydrox-ylation to give the corresponding vicinal diol. This reagent is, however, not perfect 

Osmium tetroxide reacts with the carbon-carbon double bonds in unsaturated rubber phases enhancing the contrast in TEM by the increased electron scattering of the heavy 

Several two step reactions have extended the range of OSO4 staining to materials that cannot be stained directly. Riew and Smith [195] exposed rubber modified epoxy resins to OSO4 dissolved in tetrahydrofuran (THF), which diffuses into the epoxy, speeding the reaction with the rubber. Aqueous formaldehyde was used in the staining of polyamides [1%]. Thin films of 

Osmium tetroxide is available in small ampoules either as crystals, ready to dissolve in water, or as 

Polymers containing unsatmated rubber and semicrystalline polymers are often effectively stained using OSO4. What about materials that do not show such differential staining Two examples will be described where reactive (unsaturated) materials are included into the polymer to provide reaction sites. Inclusion of a stainable unsaturated polymer was shown for cellulosics [179] and synthetic fibers [202]. The initial work focused on improvement of the properties of cellulosics by inclusion of an elastomer between the microfibrils. OSO4 staining revealed that a lamellar sheet structure was present. Marfels and Kassenbeck [202] used a similar method with polyester and nylon fibers. 

Treat the fibers overnight in a 1% solution of benzoyl peroxide catalyst, in freshly distilled isoprene. 

In Table 3.1, osmium tetroxide (OSO4) had a relatively high reduction potential (0.85 V) in acidic media, with 0s04 being reduced to osmium metal. 

For applications to organic chemistry, osmium tetroxide is most often used in neutral, aqueous media and the primary use is for the conversion of alkenes to 1,2-diols. 

Dihydroxylation of Alkenes. Criegee found that osmium tetroxide (251) is reduced by alkenes to give the cis-diol, via an intermediate osmium complex that must be decomposed.350  

Osmium tetroxide vapors are poisonous and result in damage to the respiratory tract and temporary damage to the eyes. 351 Use OSO4 powder only in a well-ventilated hood with extreme caution. 

In the absence of tertiary amines, osmium tetroxide reacts with alkenes via 1,3-dipolar addition to generate a monomeric Os(VI) ester such as 252,352 where L is a ligand that can be a solvent molecule or an added substrate such as pyridine. Sharpless et al. proposed that hydroxylation proceeds by an allowed [2-1-2]- cycloaddition reaction, producing an Os(VII) intermediate, followed by reductive insertion of the Os—C bond into an Os=0 bond.353 This complex can be decomposed in aqueous or alcoholic solution, but the hydrolysis is 

Some examples of osmium tetroxide staining are worthwhile to discuss as they describe staining methods for specific polymers. Osmium tetroxide vapor was used to stain and harden (3 days) a thin film of a two phase blend containing crystalline polychloroprene [91]. The spherulitic texture was observed, likely by a combination of staining due to the unsaturation present and due to differential absorption by the crystalline and amorphous regions in the spherulites as the crystalline 

Preferential absorption of OSO4 has been shown [95] to reveal spherulites in semicrystalline PET. Stefan and Williams [96] work on ABS-polycar-bonate blends also showed contrast by selective absorption. The dark SAN polymer, in this latter study, contains the osmium stained rubber particles while the polycarbonate was not stained. Niimoni et al. [97] found that there is often enough phase contrast in stained copolymers which have different degrees of unsaturation or functional groups like -OH, -0-, or -NH2, as they each vary in reactivity with the stain. A specially constructed pressure bomb was developed by Edwards and Phillips [98] in order to 

8 h for a bulk specimen or 1-2 h for sections. Diluted emulsion or latex particles are dropped onto coated grids and stained over 1% aqueous osmium tetroxide in a closed vessel for about 30 min. Stain times are dependent upon the form of the specimen, the mechanism of reaction, the degree of unsaturation and the temperature used. 

The second reactive inclusion method was developed [108] for microporous membranes. Stretched polypropylene, Celgard 2500 (trademark, Celanese Corp., New York), shows little fine structure after ultrathin sectioning and examination in the TEM (Fig. 4.13A), although SEM study clearly reveals a surface pore structure. In order to enhance contrast, the membrane 

LABORATORY CHEMICAL SAFETY SUMMARY OSMIUM TETROXIDE 

Vapor Density Vapor Pressure Toxicity Data 

High acute toxicity severe irritant of the eyes and respiratory tract vapor can cause serious eye damage. 

The acute toxicity of osmium tetroxide is high, and it is a severe irritant of the eyes and respiratory tract. Exposure to osmium tetroxide vapor can damage the cornea of the eye. 

Chronic exposure to osmium tetroxide can result in an accumulation of osmium compounds in the liver and kidney and damage to these organs. Osmium tetroxide has been reported to cause reproductive toxicity in animals this substance has not been shown to be carcinogenic or to show reproductive or developmental toxicity in humans. 

Solubility soluble in water (5.3% at 0 °C, 7.24% at 25 °C) soluble in many organic solvents (toluene, t-BuOH, CCI4, acetone, methyl i-butyl ether). 

Form Supplied in pale yellow solid in glass ampule, as 4 wt % solution in water, and as 2.5 wt % in t-BuOH. 

Dihydroxylation of Alkenes. The cis dihydroxylation (osmylation) of alkenes by osmium tetroxide to form d5-l,2-diols (vic-glycols) is one of the most reliable synthetic transformations (eq l).i 

The reaction has been proposed to proceed through a [3 -1- 2] or [2-1-2] pathway to give the common intermediate osmium(VI) monoglycolate ester (osmate ester), which is then hydrolyzed reductively or oxidatively to give the cd-1,2-diol (eq 2). The cis dihydroxylation of alkenes is accelerated by tertiary amines such as Pyridine, quinucUdine, and derivatives of dihydroquini-dine (DHQD) or dihydroquinine (DHQ) (eq 3). 

Due to the electrophilic nature of osmium tetroxide, electron-withdrawing groups connected to the alkene double bond retard the dihydroxylation. This is in contrast to the oxidation of alkenes by Potassium Permanganate, which preferentially attacks electron-deficient double bonds. However, in the presence of a tertiary amine such as pyridine, even the most electron-deficient alkenes can be osmylated by osmium tetroxide (eq 4). The more highly substituted double bonds are preferentially oxidized (eq 5). 

Baldwin MK, Berry PH, Esdaile DJ, et al Feeding studies in rats with mineral hydrocarbon food grade white oils. Toxicol Pathol 20(3) 426-35, 1992 

Smith JH, Mallett AK, Priston RA, et ah Ninety-day feeding study in Fischer-344 rats of highly refined petroleum-derived food-grade white oils and waxes. Toxicol Pathol 24(2) 214-30, 1996 

Smith JH, Bird MG, Fewis SC, et ah Subchronic feeding study of four white mineral oils in dogs and rats. Drug Chem 7oxlro/ 18(l) 83-103, 1995 

Nash JF Gettings SD, Diembeck W, et ah A toxicological review of topical exposure to white mineral oils. Food Chem Toxicol 34(2) 213-225, 1996 

Rabbits exposed for 30 minutes to vapor at estimated concentrations of 130mg/m developed irritation of mucous membranes and labored breathing at autopsy there was bronchopneumonia, as well as slight kidney damage. A 4-hour exposure at 400mg/m was lethal to rats.  

Walters and Keyte [102] first observed dispersed particles in blends of rubber pol)m[iers by phase contrast optical microscopy. Marsh et al [103] studied elastomer blends by both optical phase contrast and TEM. Electron microscopy was applied to study blends of natural rubber, st)n-ene-butadiene rubber (SBR), a s-polybuta-diene (PB) and chlorobutyl rubber [104]. It became obvious that both hardening of the 

Staining permits TEM observation of the dispersed phases in multiphase blends. Osmium tetroxide is the most commonly used stain for this application, while other stains have more limited application. Detailed fine structure of polymers is also made visible by staining. For example, chlorosulfonic acid staining enhances the lamellar texture of PE [105]. There are cases where a stain has been associated with a specific functional group of polymers. A specific stain for nylon, developed by Reimschuessel and Prevor-sek [106], showed the sizes of the macrofibrils and microfibrils of nylon. Fibers were immersed in 10% aqueous solution of SnCl2 for 10 min at 100°C, rinsed, placed in NH4OH solution to convert the tin chloride to insoluble SnO and then embedded for ultrathin sectioning. 

Staining of polymers can be conducted either before or after sectioning. The sample is cut into small blocks, about 1-3 mm across, and immersed in the stain solution or exposed to the vapor. Materials can be embedded and the blocks faced and then stained, especially when the stain diffuses into the polymer slowly. This method permits the sectioning and collection of the near surface material which is the most thoroughly stained. If sections can be cut prior to staining then they are stained either in the vapor, immersed in the solution, or placed on the surface of a stain droplet. 

Multiphase pol)m ers containing an unsaturated rubber phase form the largest single group of pol)m ers studied by microscopy. TTiis is due in no small measure to their ability to be stained with osmium tetroxide. The staining and hardening of rubber phases with osmium tetroxide was introduced by Andrews and Stubbs [76] and 

Andrews [107], who stained unsaturated synthetic rubbers, and then further developed by Kato [108-110], to show the morphology of rubber modified plastics and unsaturated latex particles. The polybutadiene in ABS pol)m[ ers is not apparent in unstained cross sections in the TEM, but staining results in contrast enhancement due to increased density of the unsaturated phase. Latex particles flatten and aggregate upon drying and early attempts at hardening, such as by bromination, were not considered successful. Thirty years after its first application, the method of osmium tetroxide staining is still widely and successfully applied to unsaturated rubbers and latexes. 

---

Another method for the hydroxylation of the etliylenic linkage consists in treatment of the alkene with osmium tetroxide in an inert solvent (ether or dioxan) at room temperature for several days an osmic ester is formed which either precipitates from the reaction mixture or may be isolated by evaporation of the solvent. Hydrolysis of the osmic ester in a reducing medium (in the presence of alkaline formaldehyde or of aqueous-alcoholic sodium sulphite) gives the 1 2-glycol and osmium. The glycol has the cis structure it is probably derived from the cyclic osmic ester ... 

The reagent Is expensive and poisonous, consequently the hydroxylation procedure is employed only for the conversion of rare or expensive alkenes (e.g., in the steroid field) into the glycols. Another method for hydroxylation utilises catalytic amounts of osmium tetroxide rather than the stoichiometric quantity the reagent is hydrogen peroxide in tert.-butyl alcohol This reagent converts, for example, cyc/ohexene into cis 1 2- t/ohexanedlol. 

Free cydohexene from peroxides by treating it with a saturated solution of sodium bisulphite, separate, dry and distil collect the fraction, b.p. 81-83°. Mix 8 -2 g. of cycZohexene with 55 ml. of the reagent, add a solution of 15 mg. of osmium tetroxide in anhydrous butyl alcohol and cool the mixture to 0°. Allow to stand overnight, by which time the initial orange colouration will have disappeared. Remove the solvent and unused cydohexene by distillation at atmospheric pressure and fractionate the residue under reduced pressure. Collect the fraction of b.p. 120-140°/15 mm. this solidifies almost immediately. Recrystallise from ethyl acetate The yield of pure cis-l 2 cydohexanediol, m.p. 96°, is 5 0 g. 

Concentrations in air as low as IO7 g/ms can cause lung congestion, skin damage, or eye damage. Exposure to osmium tetroxide should not exceed 0.0016 mg/ms (8-hour time weighted average - 40-hour work week). 

A catalytic enantio- and diastereoselective dihydroxylation procedure without the assistance of a directing functional group (like the allylic alcohol group in the Sharpless epox-idation) has also been developed by K.B. Sharpless (E.N. Jacobsen, 1988 H.-L. Kwong, 1990 B.M. Kim, 1990 H. Waldmann, 1992). It uses osmium tetroxide as a catalytic oxidant (as little as 20 ppm to date) and two readily available cinchona alkaloid diastereomeis, namely the 4-chlorobenzoate esters or bulky aryl ethers of dihydroquinine and dihydroquinidine (cf. p. 290% as stereosteering reagents (structures of the Os complexes see R.M. Pearlstein, 1990). The transformation lacks the high asymmetric inductions of the Sharpless epoxidation, but it is broadly applicable and insensitive to air and water. Further improvements are to be expected. 

The C—C double bond in the cyclopentene ring can be cleaved by the osmium tetroxide-periodate procedure or by photooxygenation. The methoxalyl group on C-17 can, as a typical a-dicarbonyl system, be split off with strong base and is replaced by a proton. Since this elimination occurs with retention of the most stable configuration of the cyclization equi-hbrium, the substituents at C-17 and C-18 are located trans to one another. The critical introduction of both hydrogens was thus achieved regio- and stereoselectively. 

Chemical ingenuity in using the properties of the elements and their compounds has allowed analyses to be carried out by processes analogous to the generation of hydrides. Osmium tetroxide is very volatile and can be formed easily by oxidation of osmium compounds. Some metals form volatile acetylacetonates (acac), such as iron, zinc, cobalt, chromium, and manganese (Figure 15.4). Iodides can be oxidized easily to iodine (another volatile element in itself), and carbonates or bicarbonates can be examined as COj after reaction with acid. 

With osmium tetroxide catalyst [PLATINUM-GROUP METALS, COMPOUNDS] (Vol 19)... 

CARBON - CARBON AND ARTIFICIALGRAPHITE - APPLICATIONS OF BAKED AND GRAPHITIZED CARBON] (Vol 4) -With osmium tetroxide catalyst [PLATINUM-GROUP METALS, COMPOUNDS] (Vol 19)... 

Fig. 1. Transmission electron micrograph of ABS produced by an emulsion process. Staining of the mbber bonds with osmium tetroxide provides contrast...

Oxidation. Maleic and fumaric acids are oxidized in aqueous solution by ozone [10028-15-6] (qv) (85). Products of the reaction include glyoxyhc acid [298-12-4], oxalic acid [144-62-7], and formic acid [64-18-6], Catalytic oxidation of aqueous maleic acid occurs with hydrogen peroxide [7722-84-1] in the presence of sodium tungstate(VI) [13472-45-2] (86) and sodium molybdate(VI) [7631-95-0] (87). Both catalyst systems avoid formation of tartaric acid [133-37-9] and produce i j -epoxysuccinic acid [16533-72-5] at pH values above 5. The reaction of maleic anhydride and hydrogen peroxide in an inert solvent (methylene chloride [75-09-2]) gives permaleic acid [4565-24-6], HOOC—CH=CH—CO H (88) which is useful in Baeyer-ViUiger reactions. Both maleate and fumarate [142-42-7] are hydroxylated to tartaric acid using an osmium tetroxide [20816-12-0]/io 2LX.e [15454-31 -6] catalyst system (89). 

The residue, which contains Ir, Ru, and Os, is fused with sodium peroxide at 500°C, forming soluble sodium mthenate and sodium osmate. Reaction of these salts with chlorine produces volatile tetroxides, which are separated from the reaction medium by distillation and absorbed into hydrochloric acid. The osmium can then be separated from the mthenium by boiling the chloride solution with nitric acid. Osmium forms volatile osmium tetroxide mthenium remains in solution. Ruthenium and osmium can thus be separately purified and reduced to give the metals. 

One of the main uses of osmium tetroxide is as a biological staining agent for microscopic ceU and tissue studies. Osmium tetroxide is unique in that it both fixes and stains biological material. 

Chemical degradation studies carried out on streptovaricias A and C, which are the primary components of the cmde complex, yielded substances shown ia Figure 1. Streptovaricia A (4), consumes two moles of sodium periodate to yield variciaal A [21913-68-8] (1), 0 2 200, which accounts for the ahphatic portion of the molecule, and prestreptovarone [58074-37-6] (2), C2C)H2C)N02, which accounts for the aromatic chromophore of the streptovaricias (Fig. 2). Streptovaricia G (9) is the only other streptovaricia that yields prestreptovaroae upoa treatmeat with sodium periodate. Treatmeat of streptovaricias A (4), B (5), C (6), E (8), and G (9) with sodium periodate and osmium tetroxide yields streptovarone [36108-44-8] (3), C24H23NO2, which is also produced by the reaction of prestreptovarone with sodium periodate and osmium tetroxide (4,65). A number of aliphatic products were isolated from the oxidation of streptovaricia C and its derivatives (66). 

The double bonds of avermectins react with y -chloroperbenzoic acid to give 3,4-, 8,9-, and 14,15-epoxides. The 8,9-epoxide is the primary product and can be isolated in good yield (45). The 8,9-epoxide was opened by aqueous acids to the 8,9-diol (46). The 3,4-diol can be obtained readily and regiospecificaHy by osmium tetroxide oxidation. Neither peracids nor OsO will attack the 22,23-double bond. 

Osmium tetroxide (osmic acid) 71.5°/100mm, 109.3°/400mm,... 

Cyclodecanediol has been prepared by the hydrogenation of sebacoin in the presence of Raney nickel or platinum, by the reduction of sebacoin with aluminum isopropoxide or lithium aluminum hydride, and by the oxidation of cyclodecene with osmium tetroxide and pyridine. ... 

There are also reactions which show stereoselectivity primarily because of mechanism rather than spatial bias of substrate. For instance, the conversion of an olefin to a 1,2-diol by osmium tetroxide mechanistically is a cycloaddition process which is strictly suprafacial. The hydroxylation transform has elements of both substrate and mechanism control, as illustrated by the retrosynthetic conversion of 146 to 147. The validity of the retrosynthetic removal of both... 

---