Heterocyclic compounds halide reactions

The low-temperature generation of o,o -dibromobiphenyI from BuLi and o-BraCgH4 can be effected in yields of up to 75% (376). The reactions of o,o -dilithiobiphenyl with various organometallic halides (Scheme 6) provide an example of the utility of dilithio reagents in heterocyclic compound formation. Reaction of organoboron derivatives... 

Piperazinothiazoies (2) were obtained by such a replacement reaction, Cu powder being used as catalyst (25. 26). 2-Piperidinothiazoles are obtained in a similar way (Scheme 2) (27). This catalytic reaction has been postulated in the case of benzene derivatives as a nucleophilic substitution on the copper-complexed halide in which the halogen possesses a positive character by coordination (29). For heterocyclic compounds the coordination probably occurs on the ring nitrogen. 

Hartwig and Buchwald have developed a new methodology for arylation of amines or phenols with aryl halides and palladium catalysts.17 This reaction provides a very useful strategy for the preparation of various heterocyclic compounds such as phenazines, as shown in Scheme 9.4.18... 

The formation of arylzinc reagents can also be accomplished by using electrochemical methods. With a sacrificial zinc anode and in the presence of nickel 2,2-bipyridyl, polyfunctional zinc reagents of type 36 can be prepared in excellent yields (Scheme 14) . An electrochemical conversion of aryl halides to arylzinc compounds can also be achieved by a cobalt catalysis in DMF/pyridine mixture . The mechanism of this reaction has been carefully studied . This method can also be applied to heterocyclic compounds such as 2- or 3-chloropyridine and 2- or 3-bromothiophenes . Zinc can also be elec-trochemically activated and a mixture of zinc metal and small amounts of zinc formed by electroreduction of zinc halides are very reactive toward a-bromoesters and allylic or benzylic bromides . ... 

A number of nitrogen- and sulfur-containing heterocyclic compounds are effective corrosion inhibitors (62MI11502), the imidazolines and the benzotriazoles being particularly important types. The imidazolines are derived from ethyleneamines by reaction with fatty acids the free bases (53), the fatty acid salts (54), and various derivatives obtained by reaction with anhydrides, isocyanates or alkyl halides (55) are effective inhibitors. 

Many successful regioselective syntheses of heterocycles, however, are more complex than the examples given so far. They employ condensation of two different carbonyl or halide compounds with one nitrogen base or the condensation of an amino ketone with a second difunctional compound. Such reactions cannot be rationalized in a simple way, and the literature must be consulted. 

The reaction of aryl and alkenyl halides with the Reformatsky reagent 237 in polar solvents affords a-arylacetates [105], Iodides of heterocyclic compounds such as pyridine, quinoline and pyrimidine react smoothly with Reformatsky reagents. The cross-coupling of 237 with 4-iodo-2,6-dimethyl- and 2-iodo-4,6-dimethylpyrimidine (236) occurs smoothly to form 238. But no reaction of 5-iodo-2,4-dimethylpyrimidine (239) takes place [106],... 

Halides are second only to carboxylic acids in their versatility in organic synthesis. Functional group transformations into alkenes, alkynes, amines, aldehydes, alcohols, ethers, hydrocarbons, ketones and other groups may be performed with ease in high yield. However, the major synthetic importance of halides arises from the ease by which compounds that contain this functionality may be used in carbon-carbon bond-forming reactions and in the preparation of heterocyclic compounds. 

Under microwave irradiation, carbazole reacted remarkably fast with a number of alkyl halides to give Af-alkyl derivatives of carbazole (82) (Bogdal et al., 1997). The reaction was carried out with high yields by simply mixing carbazole with an alkyl halide, which was adsorbed on potassium carbonate. A facile synthesis of a series of A-alkylpyrrolidino fullerenes (83) by phase transfer catalysis without solvent under microwave irradiation has been described by De la Cruz et al. (1998), while Adamczyk and Rege (1998) have illustrated the dramatic rate acceleration for A-sulfopropylation of heterocyclic compounds using 1,3-propane sultone under microwave irradiation affording the A-sulfopropylated compounds in 68-95% yield. 

The pKa of the methylene protons of 7 is close to that of cyanacetic ester. Thus, it was interesting to compare the reactions of these two species. We found that 7 can be acylated by various carboxylic acid halides, leading to compound 11. According to IR and NMR data 11 exists mostly as the enol-form, due to the influence of the carboranyl substituent, which strongly stabilizes conjugated double bonds.13 Compound 11 is a useful synthon for the preparation of heterocyclic compounds. It can be methylated, chlorinated and acylated twice ( compound 13). Compound 13 gives an adduct with phenylhydrazine (scheme 6). 

Carboranyl acid halides can be very easy prepared. We have studied the acylation of malononitrile and acetoacetic ester by methylcarboranyl carboxylic acid chloride (15). The reaction with malononitrile leads to the compound 17a, which exists also as a enol form, similar to compound 13. Compound 17a can be methylated to give compound 17b, a novel synthon for the preparation of wide range of heterocyclic compounds (Scheme 7). 

Recently, Buchwald and Hartwig have developed the palladium-catalyzed coupling reaction of aryl halides with amines (Scheme 165), and they have extended this reaction to the intramolecular version to give a variety of the aza-heterocyclic compounds 547 (Scheme 166).231 This methodology has provided a wide variety of alkaloids, such as indoles,232 inda-zoles,233 benzimidazoles,234 benazepines,235 phena-zines,236 carbapenems,237 the mitomycin ring system,238 a-carbolines,239 and polyheterocycles.240 Pharmacologically active natural products, such as (—)-asperlicin (550) (Scheme 167),241 dehydrobufotenine (553) (Scheme 168),242 and makaluvamine C... 

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