By Replacement of Halogeno Substituents

The replacement of (mainly nuclear) halogeno substituents by alkyl or aryl groups has been used extensively in recent years. Such replacement can be achieved with a variety of reagents, as illustrated in the following classified examples  

6-Dichloro-3-iodopyrazine (93) gave only 2,6-dichloro-3-phenylethynylpyrazine (94) [PhC CH, Cul, PdCl2 (PPh3)2, Et3N, 20°C, 1 h 87% note preferential displacement of the iodo substituent].1455 Also other examples 10.93.96-201-234-252,817,838,1114,1537,1559,1588,1607,1747 

Note Replacement of halogeno substituents with heteroaromatics appears to be confined to the use of tt-excessive systems a few sugars have also been used. 

2-Chloro-3,6-dimethylpyrazine (97) and furan (98, X = O) gave 2-(furan-2-yl)-3, 6-dimethylpyrazine (99, X = O) [Pd(PPh3)4, AcOK, AcNMe2, reflux, 6 h 75%] the same substrate (97) with thiophene (98, X = S) likewise gave 2,5-dimethyl-3-(thien-2-yl)pyrazine (99, X = S) (77%) and appropriate heterocycles, in a broadly similar way, afforded products such as 2,5-dimethyl-3-(pyrrol-2-yl)pyrazine (99, X = NH) (25%), 2,5-dimethyl-3-(oxazol-5-yl)pyrazine (100, X = O), 2,5-dimethyl-3-(thiazol-5-yl)pyrazine (100, R = S) (61%), and 2-(3, 6-dimethylpyrazin-2-yl)benzothiazole (101) (43%).323 

2-Chloropyrazine gave 2-(ot-cyanobenzyl)pyrazine (105) [PhCH2CN, NaNH2, THF, N2, 20°C, 15 min substrate j, 20°C, 2 h 73%]69 or 2-acetonylpyrazine (106) [AcMe, KNH2, NH3 (liquid)—Et20 then substrate, N2, dark, 5 min 98% for more precise details, see original].766 

2-Chloro-3,6-dimethylpyrazine (97) and furan (98, X = O) gave 2-(furan-2-yl)-3, 6-dimethylpyrazine (99, X = O) [Pd(PPh3)4, AcOK, AcNMcj, reflux, 6 h 75%] the same substrate (97) with thiophene (98, X = S) likewise gave 2,5-dimethyl- 

2-Chloropyrazine gave 2-(a-cyanobenzyl)pyrazine (105) [PhCH2CN, NiiNIC, 

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