Chlorination heterocycles

In aromatic heterocycles, chlorine is replaced by hydrogen in catalytic vapor phase hydrogenation over palladium on charcoal at 280 °C. 3,5-Dichlorotrifluoropyridine affords 2,4,6-trifluoropyridine in 75% yield. ... 

Each component is made by lithiation of a heterocycle. Chlorine-directed lithiation of the commercially available quinoline 127 goes at C-3 and reaction with formaldehyde gives the primary alcohol15128. Reaction with PBr3 replaces both OH and Cl with Br to give 125. 

Another example of the analogy between pyrazole and chlorine is provided by the alkaline cleavage of l-(2,4-dinitrophenyl)pyrazoles. As occurs with l-chloro-2,4-dinitrobenzene, the phenyl substituent bond is broken with concomitant formation of 2,4-dinitrophenol and chlorine or pyrazole anions, respectively (66AHC(6)347). Heterocyclization of iV-arylpyrazoles involving a nitrene has already been discussed (Section 4.04.2.1.8(i)). Another example, related to the Pschorr reaction, is the photochemical cyclization of (515) to (516) (80CJC1880). An unusual transfer of chlorine to the side-chain of a pyrazole derivative was observed when the amine (517 X = H, Y = NH2) was diazotized in hydrochloric acid and subsequently treated with copper powder (72TL3637). The product (517 X = Cl, Y = H) was isolated. 

A stable chloroiminium chloride (173) has been isolated from the chlorination of the heterocyclic enamine (174) (42). 

The halogen atom in benz-chloro substituted quinazolines is very stable (as in chlorobenzene), whereas the halogen atoms in positions 2 and 4 show the enhanced reactivity observed with halogen atoms on carbon atoms placed a and y to heterocyclic ring nitrogens. The chlorine atom in position 4 is more reactive than in position 2, and this property has been used to introduce two different substituents in the pyrimidine ring. ... 

In comparing the reactivity at different positions in a heterocycle, a poly-substituted derivative is sometimes used with the idea that selective reaction of the same leaving group at different positions in a single molecule gives the most clear-cut answer. However, in a polychloroazine, the mutual activation of the chlorines by one another is not identical (unless the molecule is symmetrical, in which case the... 

Nitro and azido. In benzene derivatives, the nitro group is said to rival fluorine and exceed chlorine in replaceability. The reactivity of the nitro group in heterocycles is also very high, and this... 

The 2-position is largely unreactive toward electrophiles, but nucleophilic substitution occurs there with some facility, especially in acidic medium. The protonated species is about 20 times more reactive than the neutral molecule (70BSF2705). Exhaustive chlorination in the presence of antimony trichloride gave pentachlorobenzothiazole (64GEP1168911). Direct chlorination of the parent heterocycle with aluminium or ferric... 

The double substitution of both chlorine atoms in the complex of o-dichlor-obenzene can, under certain conditions, lead to the formation of complexes of heterocycles [99, 100, 104] Scheme XX ... 

Despite the relative simplicity of the kinetics of molecular chlorination, there has so far been only one measurement of the rate coefficient with a heterocyclic compound and the need for more work in this area is indicated. Marino265 found that chlorination of thiophene by chlorine in acetic acid at 25 °C gave the second-order rate coefficient of 10.0 1.5, so that thiophene is 1.7 x 109 times as reactive as benzene in this reaction and this large rate spread is clearly consistent with the neutral and hence relatively unreactive electrophile. 

Several benzothiazinone analogs have been synthesized in an attempt to introduce hetero substituents at the a-carbon center in these heterocyclic compounds. The required a-halo-benzothiazinone intermediate 148 was prepared by chlorination with sulfiiryl chloride. This material was used successfully in an Arbuzov reaction to prepare the phosphonate diester 149,... 

Variations in the manufacturing process of 2,4,5-trichloro- and pentachlorophenol (but not 2,4-dichlorophenol) have sometimes resulted in contamination of the product by small amounts of heterocyclic impurities (4,5). Of these, the chlorinated dibenzo-p-dioxins such as TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) have received much scientific and public attention because of their real or potential toxicity 6, 7), [Chick edema factor, a curious toxicological problem to poultry producers for several years, has been shown to be composed of chlorodibenzo-p-dioxins (8).]... 

Dichloroethylphosphine has been shown to react with methyl vinyl ketone to form 2-ethyl-5-methyl-A -l,2-oxaphospholen-2-oxide (25), which has been converted to (26) by chlorination in the presence of base. The same phosphine adds to methyl acrylate in the presence of acetic acid to give the phosphine oxide (27). Further examples have appeared of the reactions of the phenylhydrazones of methyl ketones with phosphorus trichloride to produce the heterocycles (28). 

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