Dehydrochlorination of DDT

Several aromatic diamines were prepared using DDT as starting compound. 4,4 -Diaminobenzophenone was prepared using a three-stage process, including dehydrochlorination of DDT, oxidation of the 1,1-dichloro-2,2-di-(4-chlorophenyl)-ethylene thus formed and amination of 4,4 -dichlorobenzophenone [20, 23] (Scheme 2.8). 

DDT-dehydrochlorinase is an enzyme that occurs in both mammals and insects and has been studied most intensively in DDT-resistant houseflies. It catalyzes the dehydrochlorination of DDT to DDE and occurs in the soluble fraction of tissue homogenates. Although the reaction requires glutathione, it apparently serves in a catalytic role... 

Some time after the introduction of DDT as an insecticide, it was found that some insects were becoming resistant to the chemical. This was later traced to the presence of an enzyme in the resistant insects that catalyzes the dehydrochlorination of DDT to form dichlorodiphenyldichloroethylene (DDE), which is not toxic to the insects. (As expected on the basis of its structure, DDT also gives this elimination reaction when treated with base.)... 

Small amounts of DDE have been reported in some studies (Table II). The quantity rarely exceeded 5% of the recovered products. In the more common case the amount of DDE recovered did not exceed the amount in the uninoculated controls. The occurrence of DDE as a product shows no consistent relationship to organisms or conditions studied. DDE can be formed easily by the chemical dehydrochlorination of DDT. Therefore, it is reasonable to conclude that DDE is not a normal product of microbial metabolism. The pH of the media may be a factor affecting the formation of DDE. The information given in most of the studies is not suflBcient to determine if this could be the case. 

Presumably prepared by addition of fluorine to dehydrochlorinated product of DDT. c In Chemical Abstracts and in English summary of article (91). Body of paper refers to compound as p,p -dichlorodiphenyldifluorodichloroethane, but gives no analytical data. 

Table I. Dehydrochlorination-Rate Constants and Insecticidal Activity of DDT Analogs...

The higher content of DDT metabolites (DDE + DDD) compared with DDT itself (i.e., (DDE + DDD)/DDT > 1) in surface waters indicates a high degree of microbial transformation of the initial compound in the soil. The DDE and DDD are formed by DDT dehydrochlorination and dechlorination, respectively. On the whole it means that loss or leaching of toxic compounds take place from RPA formed some decades ago. 

More general cases are encountered in the metabolism of a variety of ha-log enated hydrocarbon solvents and insecticides [58]. Examples include the dehydrochlorination of 1,1,2,2-tetrachloroethane to trichloroethylene in the mouse, and of DDT (l,l,l-trichloro-2,2-bis(4-chlorophenyl)ethane) to DDE (l,l-dichloro-2,2-bis(4-chlorophenyl)ethene) [58][77]. Glutathione transferases may be involved in some of these reactions. 

Insects are also capable of forming glutathione conjugates, this being probably involved in the dehydrochlorination of the insecticide DDT, a reaction at least some insects, such as flies, are able to carry out (chap. 4, Fig. 42). 

Nitration of DDT and its dehydrochlorination product 1,1 -dichloro-2,2-di-(4-chlorophenyl)-ethylene led to the formation of bis(3-nitro-4-chlorophenylene) compounds containing 1,1,1-trichloroethane and carbonyl bridging groups [19,20]. These compounds were converted to the corresponding bis(3-amino-4-chlorophenylenes) l,l-dichloro-bis-(3-amino-4-chlorophenyl)-ethylene and 3,3 -diamino-4,4 -dichlorobenzophenone in accordance with Scheme 2.9 [5, 22, 24]. 

The apparent rate of hydrolysis and the relative abundance of reaction products is often a function of pH because alternative reaction pathways are preferred at different pH. In the case of halogenated hydrocarbons, base-catalyzed hydrolysis will result in elimination reactions while neutral hydrolysis will take place via nucleophilic displacement reactions. An example of the pH dependence of hydrolysis is illustrated by the base-catalyzed hydrolysis of the structurally similar insecticides DDT and methoxy-chlor. Under a common range of natural pH (5 to 8) the hydrolysis rate of methoxychlor is invariant while the hydrolysis of DDT is about 15-fold faster at pH 8 compared to pH 5. Only at higher pH (>8) does the hydrolysis rate of methoxychlor increase. In addition the major product of DDT hydrolysis throughout this pH range is the same (DDE), while the methoxychlor hydrolysis product shifts from the alcohol at pH 5-8 (nucleophilic substitution) to the dehydrochlorinated DMDE at pH > 8 (elimination). This illustrates the necessity to conduct detailed mechanistic experiments as a function of pH for hydrolytic reactions. 

This feat of "accelerated microevolution" involved the genetically controlled production of a dehydrochlorinating enzyme ("DDT-ase") that converted DDT to DDE. Microsomal oxidation of the latter produced polar degradable compounds. 

The main metabolite of DDT found in the liver and fats of mammals is its first dehydrochlorination product DDE, along with the unchanged DDT. A second step may occur leading to the oxidative dehydrochlorination of DDE to the substituted acid DDA, p.p -dichlorodiphenylacetlc add (Fig. 2). This metabolite is excreted as the conjugate glucuronide. 

An example of a few of these reactions that occur in our environment with several commonly used pesticides is illustrated in Figures 7-11. Fleck (15) has illustrated in Figure 7 that ultraviolet light catalyzes the decomposition of DDT. In the presence of air, one of the decomposition products is 4,4 -dichlorobenzophenone. However, when air is absent, 2,3-dichloro-l,l,4,4-tetrakis-(p-chlorophenyl)-2-butene is formed. This compound, through subsequent oxidation, may be converted into 4,4 -dichlorobenzophenone. In mammals 2,2-bis(p-chloro-phenyl) acetic acid (DDA) has been identified and shown to be excreted in the feces and urine. The mechanism of formation of DDA is believed to be an initial dehydrochlorination to DDE, which is then hydrolyzed to DDA as shown in Figure 8. Mattson et ah (29) found both DDT and DDE in most samples of human fat, and Walker et ah (44) noted low levels of these same compounds in restaurant meals. 

DDT dehydrochiorinase has been highly purified from DDT-resis-tant houseflies (47) and has been characterized as a soluble lipoprotein with a molecular weight of about 120,000 and consisting of four equal subunits. Formation of the tetramer reportedly occurs only in the presence of DDT, and GSH is required for dehydrochlorination ( ). In contrast to most GSH-S-transferases there is no evidence for the formation of a DDT-GSH adduct and no evidence that GSH is depleted during the course of the reaction. 

More recently DDT-dehydrochlorinase has been isolated and purified ( 660-fold) to apparent homogeneity from houseflies (49). In contrast to that described in earlier studies, this enzyme was found to be a dimer with subunits of molecular weights of 23,000 and 25,000. It was also found to possess substantial GSH-S-transferase activity towards 2,4-dinitrochlorobenzene and 3,4-dichloro-nitrobenzene. Based on its structure, catalytic activity and chromatographic behavior it was concluded that the purified heterodimeric DDT-dehydrochlorinase was indeed a GSH-S-transferase isozyme (49). It was proposed that instead of the nucleophilic substitution usually observed in GSH-S-transferase activity, DDT-dehydrochlorination by this enzyme involves an E2 elimination reaction in which the GS thiolate anion abstracts the hydrogen on the C-2 of DDT and this initiates the departure of the chlorine atom from C-1 ( 9) (Figure 9). 

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