A Versatile Novel Synthesis of Benzofuran and Related Compounds. II. The Vilsmeier Reaction of a-Phenoxyacetophenones

Abstract

A novel synthesis of 2-benzoylbenzofurans by the Vilsmeier reaction of a -phenoxyacetophenones are described.We have recently reported a versatile synthesis of 2-benzofurancarborylic acid derivatives by the Vilsmeier reaction of phenovyacetonitrilesl.In t h i s raction, 2-cyano group of benzofuran was partly converted to a mixture of amide, imide, and carboxcylic acid and this complex mixture made the subsequent purification troublesome.Further development of this synthesis was proceeded by using a-phenoxyacetophenones as substrate, which were easily available by the condensation of corresponding phenols and a -bromoacetophenone in t h e presence of K ~C O ~~.As shown in Scheme 1, t h e Vilsmeier reaction of a -(3,5dimethoxyphenoxy)scetophenone (I)'~ with dimethylformamide (DMF) and POCi3 afforded 2-benzoylbenzofurana ( I I a end IIb) and formylated compound (111).Usually, coupling constant (J3,7) is observed in ca. 1 Hz in nmr s p e c t r e o f 3 benzofuran derivatives, however, J3,5 does not .While proton of C-3 coupled with that of C-7 by 0.9 Hz in compound IIa, that o f C-3 appeared as sharp singlet in compound IIb.Thus the position o f formyl group of IIb was determined at C-7.Similar reactions w e r e carried out by using a -(3-methoxyphenoxy)-(IVa), a -(3ethoxyphenoxy)-(IVb), and a -(3-diethy1eminophenaxy)~cetophenone (IVc).The results are summarized in Scheme 1 and Table I.In the case of the reaction of IVe, chlorovinylformyl derivative ( V I ) and formylated compound (VII) w e r e 2 -B e n e o y l -4 , 6 -d i m e t h o x y -7 -b e n ~0 f ~r a ~~a r b 1 d e h y d e (IIb) Anal.Calcd.for C18H1405: C. 69.67; H, 4.55.found: C, 69.72; H, 4.46.Ir v m e x : 1675, 1632 (C=O) em-'; nmr (CDC13): 4.05 ( b r a, 2 x O W , 6H), 6.36 ( 8 , 5-H, lH), 7.49, 8.20 (each m, beneoyl-H, 3H, 2H), 7.62 (s, 3-H, lH), 10.49 ( s , CHO, 1H); uv A m e x : 231 nm (log a 3.52), 264 (3.39).293 (3.64), 344 (3.72); ns m/z: 310 (M').a -( 4 -F o r m y 1 -3 , 5 -d i m e t h 0 ~y p h e n o ~y ) a ~e t 0 p h e n 0 (111) Anal.Calcd.for C17H1605: C, 67.99; H, 5.37.Found: C, 67.81; 8, 5.27.Ir v m a x : 1105, 1670 (C=O) cm-l; nmr (CDC13): 3.86 (s, 2 x OMe, 6H), 5.33 (s, -OCH2-, 2H), 6.14 (s, phenoxy-2-and 6-H, 2H), 7.54, 7.98 (each m, benzoyl-H, 3H, 2H), 10.34 (s, CHO, LH); ms m/z: 300 ( M ' ) .2-Benzoyl-6-nethoxybenzofuran (Va) 4 Anal.Calcd.for C16H1203: C, 76.18; H, 4.80.