Haloalkanes and haloalkenes

Animal and human susceptibility to carbon tetrachloride hepatotoxicity is dependent on many different factors. There is substantial interspecies variation in carbon tetrachloride induced hepatotoxicity in animals due to differences in metabolic pathways among species. Based on animal models, hepatotoxicity in humans is most likely mediated from the trichloromethyl radical formed from the metabohsm of carbon tetrachloride by hepatic cytochrome p 450 2E1 Animal studies suggest differential hepatotoxicity based upon the animal s age and gender, with greater toxicity demonstrated in adult rats compared to newborns, and males compared with females. Cytochrome p-450 enzyme systems are present in the human fetus suggesting a potential for in utero fiver toxicity. Human gender differences in the metabolism of carbon tetrachloride have not been demonstrated despite potential sex steroid influences on the cytochrome p-450 system.  

The hepatotoxic effects of carbon tetrachloride are more severe in the setting of alcohol consumption. Animal studies demonstrate that the temporal relationship between ethanol ingestion and carbon tetrachloride exposure determines the severity of toxicity. Maximal hepatotoxicity is derived from ethanol ingested eighteen hours preceding exposure to carbon tetrachloride, whereas exposure to ethanol three hours prior to carbon tetrachloride exposure leads to minimal hepatotoxicity. The mechanism for this interaction is 

Cellular disruption leading to hepatocellular necrosis results from damage to cellular macromolecules by trichloromethyl radicals. Cellular disruption involves alteration of calcium homeostasis, impaired oxidative phosphorylation, and trichloromethyl radical binding to cellular proteins, nucleic acids, and induction of hpid peroxidation. Histologically there is preferential necrosis of zone three hepatocytes in the Uver acinus so called centrizonal necrosis as well as zone three steatosis. 

David K. Bonauto, C. Andrew Brodkin, William O. Robertson 

The ACGIH has set a TLV of 10 ppm over an 8 hour time weighted average and a 40 hotn work week for chloroform. Because chloroform is a potential carcinogen, the lowest possible exposure is recommended. Occupational hepatotoxicity below the ACGIH TLV has been demonstrated, with evidence of adverse effects between 2 and 10 ppm.  

Dichloromethane is commonly used as a degreaser and a paint stripper. It is metabolized in the liver by the cytochrome p-450 pathway to produce carbon monoxide. An independent pathway of metabolism occurs via conjugation with glutathione. Animal experimentation has demonstrated hepatotoxicity at near lethal concentrations of dichloromethane. Dichloromethane potentiates carbon tetrachloride hepatotoxicity in rat livers. Short term exposure to both ethanol and dichloromethane demonstrate an antagonistic relationship, while chronic exposure potentiates hepatotoxicity.  

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Anders MW. Glutathione-dependent bioactivation of haloalkanes and haloalkenes. Drug Metab Rev 2004 36(3-4) 583-594. 

Because 1,4-dichlorobenzene is a liver toxin, it probably can interact with other chemicals that are liver toxicants. These toxicants are many, and include ethanol, halogenated hydrocarbons (chloroform, carbon tetrachloride, etc ), benzene, and other haloalkanes and haloalkenes. In addition, 1,4-dichlorobenzene toxicity may also be exacerbated by concurrent exposure with acetaminophen, heavy metals (copper, iron, arsenic), aflatoxins, pyrrolizidine alkaloids (from some types of plants), high levels of vitamin A, and hepatitis viruses. Such interactions could either be additive or S5mergistic effects. 

Among the fluoride ion promoted reactions which occur in dipolar non-HBD solvents are alkylations of alcohols and ketones, esterifications, Michael additions, aldol and Knoevenagel condensations as well as eliminations for a review, see reference [600]. In particular, ionic fluorides are useful in the dehydrohalogenation of haloalkanes and haloalkenes to give alkenes and alkynes (order of reactivity R4N F > K ([18]crown-6) F > Cs F K F ). For example, tetra-n-butylammonium fluoride in AjA-dimethylformamide is an effective base for the dehydrohalogenation of 2-bromo-and 2-iodobutane under mild conditions [641] cf Eq. (5-123). 

Since haloalkanes and haloalkenes are readily available, these compounds are frequently used as starting material for the reaction method discussed but other leaving groups can be used as well. The sulfonamide group in several 5-substltuted... 

Elimination of hydrogen halides from haloalkanes and haloalkenes is an important process of synthesis of alkenes and alkynes, widely used in laboratories and industry. It is usually executed via action of strong bases NaOH, KOH, alkoxides, or trialkylamines on haloalkanes in homogeneous media. 

Common names of haloalkanes and haloalkenes consist of the common name of the alkyl group followed by the name of the halide as a separate word. Hence, the name alkyl halide is a common name for this class of compounds. In the following examples, the lUPAC name of the compound is given first, followed by its common name in parentheses. 

Gilman reagents react with haloalkanes and haloalkenes to form new carbon-carbon bonds. 

Purging a liquid containing haloalkanes or haloalkenes, which have been photochemically reacted in the presence of Ti02, with nitrogen gas and subsequently passing the purge stream... 

L. Schmerling, Condensation of haloalkanes with alkenes and haloalkenes, Friedel-Crafts and Related Reactions, Wiley, New York, 1964 Vol. 2, Chap. 26, pp. 1133-1173. 

This gives further data on another 476 acyclic compounds —alkanes, haloalkanes, alkenes, haloalkenes, diolefins, and alkynes, and methods for calculating parameters. Metal-organic Compounds. 

Sulfur tetrafluoride [7783-60-0] SF, replaces halogen in haloalkanes, haloalkenes, and aryl chlorides, but is only effective (even at elevated temperatures) in the presence of a Lewis acid catalyst. The reagent is most often used in the replacement of carbonyl oxygen with fluorine (15,16). Aldehydes and ketones react readily, particularly if no alpha-hydrogen atoms are present (eg, benzal fluoride [455-31-2] from benzaldehyde), but acids, esters, acid chlorides, and anhydrides are very sluggish. However, these reactions can be catalyzed by Lewis acids (HP, BF, etc). 

E Small molecular weight compounds of diverse structures p-Nitrophenol Disulfiram Ethanol Many haloalkenes and haloalkanes nitrosamines, benzenes... 

Table 4.16. 13C Chemical Shifts (dc in ppm) and Coupling Constants (nJCH in Hz) of Haloalkanes, Haloalkenes and Haloalkynes [86, 91 a, 255-261],...

Whereas most disproportionation reactions among the haloalkanes take place catalytically, the emphasis is on thermal disproportionation in the case of the haloalkenes and perhalogenated aromatics. 

The reactivity order also appears to correlate with the C-X bond energy, inasmuch as the tertiary alkyl halides both are more reactive and have weaker carbon-halogen bonds than either primary or secondary halides (see Table 4-6). In fact, elimination of HX from haloalkenes or haloarenes with relatively strong C-X bonds, such as chloroethene or chlorobenzene, is much less facile than for haloalkanes. Nonetheless, elimination does occur under the right conditions and constitutes one of the most useful general methods for the synthesis of alkynes. For example,... 

The empirical estimation method of Atkinson (Atkinson, 1986,1987 Kwok and Atkinson, 1995) allows the 298 K rate constants of 90% of approximately 500-600 organic compounds to be predicted to within a factor of 2 of the experimental values. Disagreements between calculated and measured rate constants most commonly occur for halogen-containing organic compounds and especially for the haloalkanes, haloalkenes and halo-genated ethers, and problems also arise for ethers, in particular for polyethers and cycloethers (Kwok and Atkinson, 1995). 

Regarding ozonation processes, the treatment with ozone leads to halogen-free oxygenated compounds (except when bromide is present), mostly aldehydes, carboxylic acids, ketoacids, ketones, etc. [189]. The evolution of analytical techniques and their combined use have allowed some researchers to identify new ozone by-products. This is the case of the work of Richardson et al. [189,190] who combined mass spectrometry and infrared spectroscopy together with derivatization methods. These authors found numerous aldehydes, ketones, dicarbonyl compounds, carboxylic acids, aldo and keto acids, and nitriles from the ozonation of Mississippi River water with 2.7-3 mg L 1 of TOC and pH about 7.5. They also identified by-products from ozonated-chlorinated (with chlorine and chloramine) water. In these cases, they found haloalkanes, haloalkenes, halo aldehydes, haloketones, haloacids, brominated compounds due to the presence of bromide ion, etc. They observed a lower formation of halocompounds formed after ozone-chlorine or chloramine oxidations than after single chlorination or chlorami-nation, showing the beneficial effect of preozonation. 

In all there are about seventy different haloalkane species which have been detected in the atmosphere, together with more than twenty haloalkenes, nearly one-hundred halo-genated cycloalkane and aromatic compounds and about forty halogenated pesticides10. In view of their greater abundances, this review will focus upon the atmospheric chemistry of CFCs, HCFCs and HFCs. 

Nucleophilic reactions with haloalkanes, haloalkenes and similar... 

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