O O R OH R O R 1 R = Cl 2 R = Br 3 R = Me 16 R = OMe 4 R = Cl 5 R = Br 6 R = Me 7 R = Cl 8 R = Br 9 R = Me HO Me HB Me HA Me Me OH R HO Ph Ph O R 10 R = Cl 12 R = Br 13 R = Me HB HA HO R Ph O R 11 R = Cl 14 R = Br 15 R = Me 17 R = OMe HB Ph Ph Ph O Ph Ph HA 123 16 + O R 23 R = Cl 24 R = Br 25 R = Me H1 H3 H2 O R H4 Me Me Me Me O R 26 R = Me 27 R = OMe O Me Me Me Me H4 H5 H1 H2 H3 R 10 15 8 3 78 2 J. CHEM. RESEARCH (S), 1998 J. Chem. Research (S), 1998, 2–3 J. Chem. Research (M), 1998, 0101–0114 Preparation of Some 6-Substituted 2,2-Dimethyl- and 2,2- and 2,4-Diphenyl-naphtho[1,2-b]pyrans W.David Cotterill, Muhammad Iqbal and Robert Livingstone* Department of Chemical and Biological Sciences, The University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK 6-Chloro-, 6-bromo-, and 6-methyl-2,2-dimethyl-, and -2,2- and -2,4-diphenyl-naptho[1,2-b]pyrans are prepared from the appropriate 4-substituted 2H-naphtho[1,2-b]pyran-2-ones and either methylmagnesium iodide or phenylmagnesium bromide; some related compounds and derivatives are also prepared and dimerisation of cylized products from the methylmagnesium iodide reactions affords dimers including a relative of isolapachenole through addition reactions of the intermediate carbonium ion.Decomposition of the respective Grignard complex obtained from 6-chloro-, 6-bromo- and 6-methyl-2H-naphtho[1,2- b]pyran-2-ones (1, 2 and 3) and methylmagnesium iodide with an aqueous solution of ammonium chloride afforded the corresponding 3-(4-chloro-, 4-bromo- and 4-methyl- 1-hydroxynaphthalen-2-yl)-1,1-dimethylprop-2-en-1-ols (4, 5 and 6), all of which decomposed on standing. The structure of the diols 4, 5 and 6 was supported by 1H NMR spectral data. The diols 4, 5 and 6 were dehydrated and cyclized in boiling acetic acid to furnish the 6-chloro- and 6-bromo- 2,2-dimethyl-2H-naphtho[1,2-b]pyrans (7 and 8) and the 2,2,6-trimethyl-2H-naphtho[1,2-b]pyran (9), respectively.Treatment of 6-chloro-2H-naphtho[1,2-b]pyran-2-one (1) with phenylmagnesium bromide, followed by decomposition of the Grignard complex with aqueous ammonium chloride solution, yielded a gum, which on boiling in acetic acid furnished 6-chloro-2,2-diphenyl-2H-naphtho[1,2-b]pyran (10) and 6-chloro-2,3-diphenyl-4H-naphtho[1,2-b]pyran (11). Compounds 10 and 11 were thus formed via the initial 1,2- and 1,4-addition of the Grignard reagent to the 6-chloronaphthopyran- 2-one (1). Similarly 6-bromo- and 6-methyl- 2H-naphtho[1,2-b]pyran-2-ones (2 and 3) afforded the respective 6-substituted 2,2-diphenyl-2H-naphtho[1,2-b]pyrans (12 and 13) and the 2,4-diphenyl-4H-naphtho[1,2-b]pyrans (14 and 15).Decomposition of the Grignard complex from 6-methoxy-2H-naphtho[1,2-b]pyran-2-one (16) gave a dark red gum, which on boiling in acetic acid afforded a small yield of 6-methoxy-2,4-diphenyl-4H-naphtho[1,2-b]pyran (17). The structures of the above compounds were supported by 1H NMR spectral data.Treatment of 6-chloro- and 6-bromo-2,2-dimethyl-2Hnaphtho[ 1,2-b]pyrans (7 and 8) in acetic acid with a few drops of sulfuric acid gave, after 2 days standing, the dimers 6 - c h l o r o / b r o m o - 3 , 4 - d i h y d r o - 2 , 2 - d i m e t h y l - 4 - ( 6 - c h l o r o / b r o m o - 2 , 2 - d i m e t h y l - 2 H- n a p h t h o [ 1 , 2 - b] p y r a n - 3 - y l ) - 2 H - naphtho[1,2-b]pyrans (23 and 24), respectively. The same treatment of 2,2,6-trimethyl-2H-naphtho[1,2-b]pyran (9) furnished a mixture (ca. 1:1) of two dimers, separated by fractional crystallization. They were identified as 3,4-dihydro- 2 , 2 , 6 - t r i m e t h y l - 4 - ( 2 , 2 , 6 - t r i m e t h y l - 2 H- n a p h t h o [ 1 , 2 - b] p y r a n - 3-yl)-2H-naphtho[1,2-b]pyran (25) and 6,6a,6b,7,8,14bh e x a h y d r o - 6 , 6 , 8 , 8 , 1 4 , 1 6 - h e x a m e t h y l d i b e n z o [ h, h p] c y c l o - penta[1,2-c:5,4,3-dpep]bis[1]benzopyran (26).The structure of dimer 26 was verified by comparing its 1H NMR spectrum and mass spectrum with those of isolapachenole (27),1 the dimer of 6-methoxy-2,2-dimethyl-2H-naphtho[1,2-b]pyran (lapachenole). The mechanism for the formation of dimers 23, 24 and 25 is probably similar to that for the dimerization of 3,3,10-trimethyl- 3H-naphtho[2,1-b]pyran.2 It is, therefore, proposed *To receive any correspondence.O R 7 R = Cl 8 R = Br 9 R = Me Me Me O R Me Me + 28 O R Me Me O R Me Me H + 29 23 24 25 H+ –H+ AcO R 21 R = Cl 22 R = Br OH Me Me OO Me O Me Me HB HA OH OH Me HB HA 18 19 20 J.CHEM. RESEARCH (S), 1998 3 that the olefinic bond of the pyran ring of a molecule of the naphthopyran is protonated to give carbonium ion 28, which reacts with another molecule of the naphthopyran to afford carbonium ion 29. This then loses a proton to form the respective dimers 23, 24 and 25. The dimerization of lapachenole (6-methoxy-2,2-dimethyl- 2H-naphtho[1,2-b]pyran) under acidic conditions affords only isolapachenole (27) (85%),3 due to the activating effect of the methoxy group at the 6-position of the monomer.With the weaker activating methyl group at the 6-position, dimer 26 (49%), similar in structure to isolapachenole, and dimer 25 (35%) are formed. However, with the deactivating halogeno group at the 6-position in compounds 7 and 8 only the respective dimer 23 (79%) or 24 (69%) is formed. Treatment of the diols 4 and 5 in pyridine with acetic anhydride resulted in the acetylation of the more nucleophilic phenolic OH to give the monoacetates, 3-(1-acetoxy- 4-chloro/bromo-2-naphthyl)-1,1-dimethylprop-2-en-1-ol (21 and 22, respectively).To complete the series of dimethylnaphthopyrans, 2,2-dimethyl-2H-naphtho[2,3-b]pyran (20) was prepared. Decomposition of the Grignard complex from 2Hnaphtho[ 2,3-b]pyran-2-one (18) and methylmagnesium iodide with aqueous ammonium chloride solution yielded 3-(3-hydroxy-2-naphthyl)-1,1-dimethylprop-2-en-1-ol (19), which on boiling with acetic acid gave 2,2-dimethyl-2Hnaphtho[ 2,3-b]pyran (20). Techniques used: IR and 1H NMR, MS References: 15 Figures: 2 Tables 1–4: 1H NMR data Received, 16th June 1997; Accepted, 17th September 1997 Paper E/7/04178K References cited in this synopsis 1 W. D. Cotterill, R. Livingstone, K. D. Bartle and D. W. Jones, Tetrahedron, 1968, 24, 1981. 2 W. D. Cotterill, S. A. Fairbank, R. Livingstone and R. Peace, J. Chem. Res., 1994, (S) 254; (M) 1489. 3 R. Livingstone and M. C. Whiting, J. Chem. Soc., 1955, 3631.