Substitutions Chlorination

Other interesting regioselective reactions are carried out within the synthesis of nitrofurantoin. Benzaidehyde semicarbazone substitutes chlorine in chloroacetic ester with the most nucleophilic hydrazone nitrogen atom. Transamidation of the ester occurs with the di-protic outer nitrogen atom. Only one nucleophilic nitrogen atom remains in the cyclization product and reacts exclusively with carbonyl compounds. 

The process involving aHyl alcohol has not been iadustriaHy adopted because of the high production cost of this alcohol However, if the aHyl alcohol production cost can be markedly reduced, and also if the evaluated cost of hydrogen chloride, which is obtained as a by-product from the substitutive chlorination reaction, is cheap, then this process would have commercial potential. The high temperature propylene—chlorination process was started by SheH Chemical Corporation ia 1945 as an iadustrial process (1). The reaction conditions are a temperature of 500°C, residence time 2—3 s, pressure 1.5 MPa (218 psi), and an excess of propylene to chlorine. The yield of aHyl chloride is 75—80% and the main by-product is dichloropropane, which is obtained as a result of addition of chlorine. Other by-products iaclude monochioropropenes, dichloropropenes, 1,5-hexadiene. At low temperatures, the amount of... 

Methane, chlorine, and recycled chloromethanes are fed to a tubular reactor at a reactor temperature of 490—530°C to yield all four chlorinated methane derivatives (14). Similarly, chlorination of ethane produces ethyl chloride and higher chlorinated ethanes. The process is employed commercially to produce l,l,l-trichloroethane. l,l,l-Trichloroethane is also produced via chlorination of 1,1-dichloroethane with l,l,2-trichloroethane as a coproduct (15). Hexachlorocyclopentadiene is formed by a complex series of chlorination, cyclization, and dechlorination reactions. First, substitutive chlorination of pentanes is carried out by either photochemical or thermal methods to give a product with 6—7 atoms of chlorine per mole of pentane. The polychloropentane product mixed with excess chlorine is then passed through a porous bed of Fuller s earth or silica at 350—500°C to give hexachlorocyclopentadiene. Cyclopentadiene is another possible feedstock for the production of hexachlorocyclopentadiene. 

Addition Chlorination. Chlorination of olefins such as ethylene, by the addition of chlorine, is a commercially important process and can be carried out either as a catalytic vapor- or Hquid-phase process (16). The reaction is influenced by light, the walls of the reactor vessel, and inhibitors such as oxygen, and proceeds by a radical-chain mechanism. Ionic addition mechanisms can be maximized and accelerated by the use of a Lewis acid such as ferric chloride, aluminum chloride, antimony pentachloride, or cupric chloride. A typical commercial process for the preparation of 1,2-dichloroethane is the chlorination of ethylene at 40—50°C in the presence of ferric chloride (17). The introduction of 5% air to the chlorine feed prevents unwanted substitution chlorination of the 1,2-dichloroethane to generate by-product l,l,2-trichloroethane. The addition of chlorine to tetrachloroethylene using photochemical conditions has been investigated (18). This chlorination, which is strongly inhibited by oxygen, probably proceeds by a radical-chain mechanism as shown in equations 9—13. 

Dichloroethane is produced by the vapor- (28) or Hquid-phase chlorination of ethylene. Most Hquid-phase processes use small amounts of ferric chloride as the catalyst. Other catalysts claimed in the patent Hterature include aluminum chloride, antimony pentachloride, and cupric chloride and an ammonium, alkaU, or alkaline-earth tetrachloroferrate (29). The chlorination is carried out at 40—50°C with 5% air or other free-radical inhibitors (30) added to prevent substitution chlorination of the product. Selectivities under these conditions are nearly stoichiometric to the desired product. The exothermic heat of reaction vapori2es the 1,2-dichloroethane product, which is purified by distillation. 

Although the nature of the general polar effect suggested by Kamernitzsky and Akhrem " to account for axial attack in unhindered ketones is not clear, several groups have reported electrostatic interactions affect the course of borohydride reductions. Thus the keto acid (5a) is not reduced by boro-hydride but its ester (5b) is reduced rapidly further, the reduction of the ester (6b) takes place much more rapidly than that of the acid (6a). Spectroscopic data eliminate the possibility that in (5a) there is an interaction between the acid and ketone groups (e.g. formation of a lactol). The results have been attributed to a direct repulsion by the carboxylate ion as the borohydride ion approaches. " By contrast, House and co-workers observed no electrostatic effect on the stereochemistry of reduction of the keto acid (7). However, in this compound the acid group may occupy conformations in which it does not shield the ketone. Henbest reported that substituting chlorine... 

It may not be appropriate to compare the thermal stability characteristics of VC/VAc copolymer to that of a VC homopolymer (PVC). The copolymerization would involve different kinetics and mechanism as compared to homopolymerization resulting structurally in quite different polymers. Hence, copolymerization of VC with VAc cannot be regarded as a substitution of chlorines in PVC by acetate groups. To eliminate the possibility of these differences Naqvi [45] substituted chlorines in PVC by acetate groups, using crown ethers (18-crown-6) to solubilize potassium acetate in organic solvents, and studied the thermal stability of the modified PVC. Following is the mechanism of the substitution reaction ... 

The anionic moiety can substitute chlorines in PVC by an Sn mechanism [Eq. (31)]. The reaction can also take place by an Sn mechanism. This would involve the formation of a cationic center on the polymer backbone... 

The exocyclic methylene C —C double bond can be reduced to give the corresponding methyl-substituted chlorin.25... 

Sensitivity for fluorine-substituted < chlorine-substituted < broaine-substituted < iodine-substituted coapounds... 

An elastomer made by substituting chlorine and sulphonyl chloride groups into polyethylene. The material is best known by the trade name Hypalon, which is the DuPont trade mark for their brand of chlorosulphonated polyethylene. 

Zitko, V. 1992. Patterns of 2,3,7,8-substituted chlorinated dibenzodioxins and dibenzofurans in aquatic fauna. 

The a-selectivity for carbon radical addition to propadiene (la) is retained on substituting chlorine or fluorine for hydrogen in radicals of the type CX3 (X=F, Cl), no matter whether the reaction is conducted in the liquid or in the gas phase (Table 11.4) [14, 49-51]. /3-Selective addition to allenes becomes progressively more important for the CC13 radical with an increase in number of methyl substituents [14, 47]. For example, treatment of optically active (P)-(+)-2,4-dimethylpenta-2,3-diene [(P)-(lc)] with BrCCl3 affords a 59 41 mixture of a- and /3-monoadducts [47]. The a-addition product consists of a 20 80 mixture of E- and Z-stereoisomers, whereas the product of /3-addition exclusively exhibits the Z-configuration. The fraction of 2,4-dimethylpenta-2,3-diene (P)-(lc) that was recovered from this reaction mixture had completely retained its optical activity. These results indicate that the a-and the /3-CCl3 addition proceed under kinetic control. If one of the addition steps were reversible, at least partial racemization would inevitably have taken place. 

Thus, ketone enolates easily substitute chlorine in position 2 of the electrophilic nucleus of pyrazine (1,4-diazabenzene), and even in the dark, the reaction proceeds via the Sj l mechanism (Carver et al. 1981). It is expected that the introduction of the second chlorine in the ortho position to 4-nitrogen in the electrophilic nucleus of pyrazine promotes the ion-radical pathway even more effectively. However, 2,6-dichloropyrazine in the dark or subjected to light reacts with the same nucleophiles by Sr.,2 and not S nI mechanism (Carver et al. 1983). The authors are of the opinion that two halogens in the pyrazine cycle facilitate the formation of a-complex to the extent that deha-logenation of anion-radicals in solution and a subsequent nucleophilic attack of free pyrazine radical become virtually impossible. Thus, the reaction may either involve or exclude the intermediate a-complex, and only special identification experiments can tell which is the true one. 

Many of the substitution reactions of 2,3 -bipyridine have been conducted using anabasine (12 R = H) as starting material, which presumably is dehydrogenated to 2,3 -bipyridine prior to substitution. Chlorination of anabasine (as the hydrochloride) at 220-230°C affords 5-chloro-2,3 -bipyri-dine. Isoanabasine [2-(3-piperidyl)pyridine] behaves similarly on chlorination. 2,3 -Bipyridine is fully chlorinated to octachloro-2,3 -bipyridine by... 

Commerciol Dichlorohydrin consists of the above two isomers, the proportions of which depend on method of prepn d 1.36-1.39, bp 175-80°, flash p 74°, Glycerol was the main source for the prepn of glycerol chloro-hydrins until the process for direct substitutive chlorination of propylene to allyl chloride paved the way for synthesis by chlorohydrination of allyl chloride. In the synthesis from glycerol, excess HCI is used in the presence of 4% acetic acid. The reaction is run at 130° to yield 90% of product which is mainly the a,y-form. Synthesis from propylene yields a mixt of approx 70% a,/8-form 8c 30% a,y-form. Addn of HCI to epichlorohydrin, CH2 CHCH> Cl, at... 

Chloro-N-methyl-N-(trichloromethyl)aniline is fluorinated with antimony(III) fluoride in the absence of catalysts while catalysis with antimony(V) chloride is required to substitute chlorine atoms by fluorine in the trichloromethyl group of 4-chloro-A -(trichloromethyl)-/V-(trifluoromethyl)aniline (8).86,87... 

Nitronium tetrafluoroborate in the presence of pyridine poly(hydrogen fluoride) (PPHF) can be used to substitute chlorine or bromine in adamantanes and other hydrocarbons (see Table 21).90... 

For alkyl substituents, electrophilic substitution (chlorination, bromination, acetylation, trifluoroacetylation, formylation, hydrogen exchange) of 2-alkylthiophenes happens mainly... 

Triazine is resistant to electrophilic substitution. Chlorination requires vigorous conditions, and yields are low bromination is a more efficient process (Scheme 6). The reagents employed in the attempted sulfonation or nitration preferentially hydrolyze the ring (63AG(E)309). Recently, Korolev and Mal tseva have reported that 1,3,5-triazine is protonated and hydrated to form the cation shown in equation (2) (75ZOR2613). 

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