Chlorine displacement

Halogen atoms on benzazole rings can be activated toward nucleophilic displacement by electron-withdrawing groups. Thus azide ion displaces chlorine from 5-chloro-4-nitro- and 4-chloro-7-nitro-benzofuroxan (65JCS5958). 

DECHLOR 108 is a solution that has been developed for use in treating chlorinated solvents in waste oU. According to the vendor, the solution displaces chlorine molecules and converts them into nontoxic substances, while leaving the waste oil supply unaffected. 

We have therefore deduced from the formula for the heat of formation of ionic compounds the important rule that the halogens replace one another in the order F2, Cl2, Br2, I2. There are ho known exceptions to this rule. Fluorine displaces chlorine, bromine and iodine from all chlorides, bromides and iodides, while chlorine and bromine displace iodine from all iodides. It is to be expected that the same substitution reactions can take place with the chal-cogens 02, S, Se and Te, and, since the heat of formation of the oxides is, as a rule, greater than that of the sulphides, the reactions of the type... 

Miller passed fluorine over liquid chloroform, pentachloroethane, 1,1,2,2-tetrachloro-ethane, tetrachloroethene, and trichloroethene. He was able to control the reactions, though mixtures of products resulted. Replacements of hydrogen and of chlorine, additions to C = C bonds, dimerizations (particularly at C = C bonds) and chlorination (by displaced chlorine) all occurred radical mechanisms were thought to prevail. 

On the other hand, from oxygen compounds, iodine will displace chlorine ... 

Hydrogen fluoride can displace chlorines on either side chain or nucleus (especially 2-chloro), and antimony fluoride is specific for all chlorinated methyl groups. Sodium fluoride initially replaces a 4-chloro group (82JFC495). Some of these processes have been subjected to kinetic investigation, which demonstrated that in polar, aprotic solvents fluorine-chlorine exchange is a pseudo first-order, consecutive reaction (87JFC373). 

Br . Aq. Similarly, bromine displaces iodine from a soluble iodide. But iodine displaces chlorine from the nearly insoluble silver chloride. Here, the iodine is still less soluble than the chloride and as chloride dissolves, the less soluble and therefore non-ionised iodide is formed. 

The reaction of the fused 5,7-dihalopyrimidine (19) to form the 7-methoxy derivative (20) also shows that the more readily displaced chlorine is next to the azole ring (67T675). Hydrazinolysis of the isoquinoline analogue (21) is stepwise with initial 4-substitution (22). The difference in reactivity at C-4 and C-6 in (22) is sufficient for selective acid hydrolysis of the hydrazino group in (22). Reductive cleavage of the hydrazino C—N bond is achieved in the usual manner by the reaction of its tosyl derivative with alkali (75JCS(Pi)2l90). 

The search for endothelin antagonists as potential compounds for treating cardiovascular disease was noted in Chapter 5 (see atrasentan). A composed with a considerably simpler structure incorporates a pyrimidine ring in the side chain. Condensation of benzophenone (94) with ethyl chloro-acetate and sodium methoxide initially proceeds to addition of the enolate from the acetate to the benzophenone carbonyl. The aUcoxide anion on the first-formed quaternary carbon then displaces chlorine on the acetate to leave behind the oxirane in the observed product (95). Methanolysis of the epoxide in the product in the presence of boron triflor-ide leads to the ether-alcohol (96). Reaction of this with the pyrimidine (97) in the presence of base leads to displacement of the methanesulfonyl group by the aUcoxide from 96. Saponification of the ester group in that product gives the corresponding acid, ambrisentan (98). " ... 

Similar results have been obtained with 4,5-dimethoxycarbonyl- and 4-phenyl-l,2,3-triazolides, which displace chlorine from ethyl chloroacetate or /3 -chloropropionate to give both 1-N- and 2-lV-alkylated products. The highest 2-N to l-N selectivity was ca. 5 1 with the base triethylamine in DMF. Furthermore, triazolides add to alkynes to give Michael adducts at the 2-position exclusively (73T3285, 73JOC2708). 

Introducincr Substituents About Silicon. With displaceable chlorine atoms at all the required positions, we took advantage of the unique chemistry of silicon to introduce a wide variety of substituents about the silicon atom, since the Si-Cl bonds are much more reactive than the C-Cl bond. Typically, organometallic reagents are used, and since the chlorines on silicon can be replaced stepwise, the synthesis offers considerable flexibility (Equation 3). 

The feedstock supply is limited by the volume available from the paper industry. Introduction of chlorine into a molecule means that great care must be taken to remove it all and stringent controls put in place to ensure that the techniques employed for its total removal (below ppb levels) are effective. The use of sodium acetate as a nucleophile to displace chlorine results in the generation of sodium chloride in stoichiometric amounts as an effluent which must be disposed of. The acetic acid generated in the next step must also be either disposed of or cleaned up for recycling. 

A remarkable and valuable reaction takes place when aromatic acid chlorides are reaeted with phospholes and the mixture then treated with water. The products possess the 1,2-dihydrophos-phinine ring structure. Apparently the nucleophilic phosphorus displaces chlorine from the acid chloride water then adds to the phosphonium ion to form a pentacoordinate intermediate (86) which undergoes the ring expansion to the phosphinine derivative (87) (Scheme 9). 

Amino silanes react to produce phosphonous amides MeP (NR2)2 (7.179), and silver cyanide or thiocyanate produces the corresponding cyano derivative (6.168). Hydrogen bromide displaces chlorine to give methylphosphonous dibromide (6.169). 

It has been found that the reaction at the C-Br or the C-Cl bond of l-bromo-4-chlorobutane can be controlled by changing the solvent for the reaction. For instance, the regiospeciflcity at the C-Br bond in the S 2 alkylation reaction with RZnBr in the presence of a Pd-PEPPSI-/-Pr catalyst when the DMI/THF ratio is 1/2 is 12.2 1 or 92%. DMI is dimethylimidazolidinone with an e = 37.6, whereas THF has an e = 7.5. However, when the DMI/THF = 2/1, the reaction occurs at the C—Cl bond. This means that the two reactions can be performed in one pot that is, one RZnBr reagent is used to displace bromine and, when this reaction is complete, the solvent composition is changed and a different RZnBr reagent is used to displace chlorine. Both reactions occur at room temperature, with yields of 70%. 

Chlorotrityl chloride resin is normally supphed with a displaceable chlorine content of 1.0-1.6 mmol/g. For the purposes of peptide synthesis, this substitution can sometimes be too high and can be reduced by treating the resin with a sub-stoichiometric amount of amino acid derivative and then capping imreacted sites with MeOH. 

A comparison of the energetics of the reaction in Figure 7.1 and that in Figure 7.2 makes it is clear that iodide will displace chlorine from chlo-romethane, but chloride ion will not displace iodide from iodomethane. The first reaction is exothermic and spontaneous, whereas the second is endothermic and nonspontaneous. The reaction of iodide ion and chloromethane is not expected to be reversible because the chloride ion + iodomethane reaction does not generate enough energy to overcome the activation barrier. This simple analysis has provided a great deal of information about these reactions, which is the point of this entire section. 

Sodium pentacarbonylmanganate(—i) displaces chlorine from 1,2-dichloro-tetrafluorocyclobutene, and fluorine from perfluororgrclopentene, to give (8) and (9a), respectively. 

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