Pyridine 2-bromo-5-cyano

The greenish-blue dye (117) (82) is prepared in a similar fashion, replacing bromo with cyano by using cuprous cyanide, pyridine, and 2-methoxyethanol as solvent at 85°C. 

Ethyl substitution at the imidazole 5-position (469) was found to increase potency over the unsubstituted analogue (468), while methyl substitution (470) had a slightly deleterious effect on binding (Table 6.41). Chloro (491), bromo (492), cyano (493) and fluoromethyl (494) substitution at this position were all well tolerated (Table 6.43). Introduction of a chloro-substituted pyridine (475) in place of the more usual / -chlorophenyl group (470) resulted in a slight loss of affinity for the CBi receptor, as did replacement of the p-chloro group of (470) with bromo (471), fluoro (472) and in particular, met-hoxy (473). Trifluoromethyl substitution (474) however, was well tolerated. 

Bromo substituents in the 6- and 6 -positions of 2,2 -bipyridines are particularly reactive, being readily converted to amino,cyano, ° al-koxyl, hydrazino, chloro, and hydrogen groups and by way of the corresponding lithio derivatives to carboxyl, methyl, aldehyde or alkylcarbonyl, and other groupings. 6,6 -Dibromo-2,2 -bi-pyridine also reacts with the disodium derivatives of polyethylene glycols to give crown ethers akin to 100, and 6,6 -bis(chloromethyl)-2,2 -bi-pyridine " and the derived 6,6 -bis(mercaptomethyl)-2,2 -bipyridine... 

Nucleophilic substitution reactions have been less extensively investigated. The exchange reaction of 4-bromo-6,7-dimethyl-7,6-borazarothieno[3,2-c]pyridine with copper(I) salts in HMPT at 150-180 °C gives the chloro, iodo and cyano derivatives in good yields (e.g. equation 52). 

In the photostimulated reaction of SCH2C02Et ions with 2-bromo-3-cyano or 3-bromo-4-cyano pyridines, the substitution product formed is deprotonated, and the anion formed reacts with the cyano group to give ultimately the ring closure substitution products 304 (90%) and 305 (98%), respectively. The yields are high, because in these cases fragmentation of the radical-anion intermediates does not take place288. 

Displacement of the chloro substituent from pyrazines by the cyano group has not been satisfactorily accomplished (866), but many cyanopyrazines have been prepared from the bromo analogues. Karmas and Spoerri (866) prepared 11 cyanopyrazines with mono-, di-, or trialkyl or phenyl substituents from the corresponding bromo compounds and cuprous cyanide in refluxing dry 4-picoline, but the procedure was not suitable for the preparation of 2-cyanopyrazine (866). It was prepared in 29% yield when the reaction was performed in pyridine (866). Another preparation of 2-cyano-3-phenylpyrazine from the bromo analogue has also been reported (1024). 

When the reaction with propargyl alcohol is run in an amine solution at elevated temperature, the alkynylated product first formed is further transformed by a cyclization reaction with the pyridine nitrogen 3-piperidinoindolizine (35) is formed (36% yield) in piperidine at 80°C. Corresponding cyclization products result from the reaction with 1-bromoisoquinoline or 2-bromoquinoline with propargyl alcohol (80BCJ3273). Alkynylation (38) of 2-chloro-, 3-bromo-, and 4-iodopyrimi-dines, which are vicinally substituted by a cyano, carbamoyl, or ethoxy-carbonyl group, has been effected with phenylacetylene by heating the... 

Fig. 11-1. Intramolecular electronic effects in the adsorption of meta- and para-% ih-stituted pyridines on (a) alumina and (b) silica (15,24). 1, 4-amino 2, 3, 4-dimethyl 3, 4-methyl 4, 4-ethyl 5, 3-methyl 6, pyridine 7, 3-hydroxy 8, 4-chloro 9. 4-aldehyde 10,3-acetyl 11,3-iodo 12,3-aldehyde 13, 3-chloro 14, 3-bromo 15. 4-cyano 16, 3-cyano 17, 3,5-dichloro. [The plots do not include points for the compound 3-aminopyridine see discussion of Ref (/5).]...

---