Toxicity of reagents

The high toxicity of reagents CO, HF and BF3 necessitated all reactions to be conducted in a fume-hood. 

The immobilization of reagents onto sorbents often results in increase of their sensitivity and, in some cases, selectivity, allows to simplify the analysis and to avoid necessity of use of toxic organic solvents. At the same time silicas are characterized by absence of swelling, thenual and chemical stability, rapid achievement of heterogeneous equilibrium. 

Since osmium tetroxide is expensive and toxic, alternate reagents were also explored. This has led to the use of potassium permanganate by two different groups. ... 

The actual catalyst is a complex formed from osmium tetroxide and a chiral ligand, e.g. dihydroquinine (DHQ) 9, dihydroquinidine (DHQD), Zj -dihydroqui-nine-phthalazine 10 or the respective dihydroquinidine derivative. The expensive and toxic osmium tetroxide is employed in small amounts only, together with a less expensive co-oxidant, e.g. potassium hexacyanoferrate(lll), which is used in stoichiometric quantities. The chiral ligand is also required in small amounts only. For the bench chemist, the procedure for the asymmetric fihydroxylation has been simplified with commercially available mixtures of reagents, e.g. AD-mix-a or AD-mix-/3, ° containing the appropriate cinchona alkaloid derivative ... 

As alkylating agent an alkyl halide, alkyl tosylate or dialkyl sulfate is used in most cases the latter type of reagent is often used in the preparation of methyl and ethyl ethers by employing dimethyl sulfate and diethyl sulfate respectively. Dimethyl sulfate is an excellent methylating agent, but is acutely toxic as well as carcinogenic." ... 

Alkyl uracyls have been known for some time to act as diuretic agents in experimental animals. The toxicity of these agents precluded their use in the clinic. Appropriate modification of the molecule did, however, yield diuretic agents with application in man. Reaction of allylamine with ethyl isocyanate affords the urea, 89 (the same product can of course be obtained from the same reagents with reversed functionality). Condensation with ethyl cyanoacetate affords aminotetradine (90). In... 

Osmium tetroxide, reaction with alkenes, 235-236 toxicity of, 235 Oxalic add, structure of, 753 Oxaloacetic acid, structure of, 753 Oxetane, reaction with Grignard reagents, 680 Oxidation, 233, 348 alcohols, 623-626 aldehydes, 700-701 aldoses, 992-994 alkenes, 233-236 biological, 625-626 phenols, 631 sulfides, 670 thiols, 668... 

The main drawback to this reaction is the toxicity of diazomethane and some of its precursors. Diazomethane is also potentially explosive. Trimethylsilyldia-zomethane is an alternative reagent,42 which is safer and frequently used in preparation of methyl esters from carboxylic acids.43 Trimethylsilyldiazomethane also O-methylates alcohols.44 The latter reactions occur in the presence of fluoroboric acid in dichloromethane. 

The toxicity of 3-methylindole has been attributed to methyleneindolenine trapping of nitrogen and sulfur nucleophiles.57 60-62 Likewise, the ene-imine shown in Scheme 7.9 readily reacted with hydroquinone nucleophiles, resulting in head-to-tail products. Shown in Fig. 7.6 is the 13C-NMR spectrum of a 13C-labeled ene-imine generated by reductive activation. The presence of the methylene center of the ene-imine is apparent at 98 ppm, along with starting material at 58 ppm and an internal redox reaction product at 18 ppm. Thus, the reactive ene-imine actually builds up in solution and can be used as a synthetic reagent. 

Stoichiometric use of a tin reagent to prepare the phenylacetone 4 Toxicity of tin compounds, and operational inefficiency based on high molecular weight of reagent and excessive chromatography required to reject tin residues... 

One-electron reduction or oxidation of organic compounds provides a useful method for the generation of anion radicals or cation radicals, respectively. These methods are used as key processes in radical reactions. Redox properties of transition metals can be utilized for the efficient one-electron reduction or oxidation (Scheme 1). In particular, the redox function of early transition metals including titanium, vanadium, and manganese has been of synthetic potential from this point of view [1-8]. The synthetic limitation exists in the use of a stoichiometric or excess amount of metallic reductants or oxidants to complete the reaction. Generally, the construction of a catalytic redox cycle for one-electron reduction is difficult to achieve. A catalytic system should be constructed to avoid the use of such amounts of expensive and/or toxic metallic reagents. 

Due to the toxicity of tin reagents, a new radical elimination without using Bu3SnH is highly desirable. B arton has reported that nitro olefins are converted into olefins via radical elimination of P-nitro trithiocarbonates (Eq. 7.116).160 The Michael addition of trithiocarbonate to nitroalke-nes is carried out in CS2 to avoid the addition of EtSH. 

The toxicity of cyanide has led to the development of alternative lixiviants for gold and silver see also Sections 9.17.3.2 and 9.17.3.3. Thiosulfate is potentially a cheaper reagent for use in alkaline or near-neutral solutions in the presence of a mild oxidant such as dioxygen,41-48... 

Some of the disadvantages of the Stille reaction, e. g. the low reactivity of some substrates, separation difficulties in chromatography, and the toxicity of tin compounds, have been ameliorated by recent efforts to improve the procedure. Curran has, in a series of papers, reported the development of the concept of fluorous chemistry, in which the special solubility properties of perfluorinated or partly fluorinated reagents and solvents are put to good use [45]. In short, fluorinated solvents are well known for their insolubility in standard organic solvents or water. If a compound contains a sufficient number of fluorine atoms it will partition to the fluorous phase, if such a phase is present. An extraction procedure would thus give rise to a three-phase solution enabling ready separation of fluorinated from nonfluorinated compounds. 

Selenium dioxide is also an oxygen donor to alkenes. In this case, however, the initial reaction of the double bond is with the selenium center followed by two pericyclic steps. After hydrolysis of the organo-selenium intermediate, the result is a hydroxylation at the allylic carbon position65. Thus, limonene (2) yields racemic p-mentha-l,8(9)-dien-4-ol66. The high toxicity of selenium intermediates and prevalence of many rearrangements has limited the widespread use of the reagent in synthesis. 

In addition, many other aspects must be considered when developing a catalytic reaction for industrial use these include catalyst separation, stability and poisoning, handling problems, space-time yield, process sensitivity and robustness, toxicity of metals and reagent, and safety aspects, as well as the need for high-pressure equipment. 

All drains in a toxic laboratory with exception of those from the toilets should lead to a toxic sump. The toxic sump should be fitted with the wherewithal to permit addition of reagents, agitation, and sampling, as well as adequate indicators and alarms to highlight malfunctions. Valving should be convenient to operate and the system should feature parallel tanks so one batch can be treated while the lab continues to discharge to the other tank. Provision should be provided to pump out contents when untreatable. 

Chloro-2-fluoroethane, easily obtained3 from fluoroethanol, was found to be non-toxic. A concentration of 0-184 mg./l. failed to kill any animals, whereas a similar concentration of fluoroethanol or of methyl fluoroacetate would have killed some 50 per cent of a batch of rabbits, guinea-pigs or rats. The chlorine atom in chlorofluoroethane was found to be un-reactive towards a variety of reagents, and this fact no doubt... 

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