3.4- Dihydro-2//-l-benzopyrans

Keywords Acetals, Acylals, Allylations, Bismuth(III), 3,4-Dihydro-2//-l -benzopyrans, Ene reactions, Epoxide-olefin cyclizations, Piperidines, Tetrahydro-quinolines, THP ethers... 

Scheme 3 Bismuth(III) triflate-catalyzed synthesis of substituted 3,4-dihydro-2//-l-benzopyrans...

Baumy et al. (27) determined the binding constants for two 3,4-dihydro-2//-l-benzopyran derivatives of /3-CD. These binding constants were then used to calculate the optimal concentration of chiral selector for the enantioseparation of the two compounds. The calculation of the optimal concentration of the chiral selector was performed according to Eq. (18). Good agreement was found between the calculated and experimentally observed optimum concentrations for the two compounds. 

Under similar conditions a low asymmetric induction is reported for the cyclization of the 2-[( )-pentenyl]phenol 3, which gives the 2,2-disubstituted 3,4-dihydro-2//-l-benzopyran 4 in 80% yield but only 10% ee60. 

Hammarstrom, E. et ah. Synthesis of novel 5-substituted 3-amino-3,4-dihydro-2//-l-benzopyran derivatives and their interactions with the S-HTi receptor, J. Med. Chem., 43, 2837, 2000. 

Chroman (3,4-dihydro-2//-l-benzopyran) is derived from 3,4-dihydro-2if-pyran by annulation of a benzene ring. Its structural isomer is the isochroman 1. 2-Phenylchroman 2 is known as... 

Thionyl chloride is one of the most common and effective reagents to effect cyclodehydration of 2-acylamino ketones. For example, Litak and Kauffman refluxed 446 in SOCI2 and isolated 4-[2-(3,4-dihydro-2//-l-benzopyran-6-yl)oxazol-5-ylpyridine 447 in excellent yield (Scheme 1.123). Both 447 and 441 were starting materials for reactive fluorescent stains to be used in fluorescence microscopy. Reck and Friedrichsen refluxed 448 in SOCl2/chloroform and prepared 4-(methoxy-carbonyl)-2-methyl-5-oxazoleacetic acid methyl ester 449 (Scheme 1.123). This material was a precursor of the novel diene 4-methoxy-2-methyl-furo[3,4-ti]ox-azole-6-carboxylic acid methyl ester 450. 

C H,jN 555S-29-2) see Isoaminile 6-methyl-4-phenyl-3,4-dihydro-2H-l-benzopyran-2-one (C (jH 402 40546-94-9) see Tolterodine... 

A mixture of 66.13 g (0.159 mol) of methyl (R,S)-6-acetyl-3,4-dihydro-7-[5-[(methylsufonyl)oxy]pentyloxy]-2H-l-benzopyran-2-carboxylate, 30.99 g (0.159 mol) of l-[2,4-dihydroxy-3-propylphenyl)ethanone, 33.07 g (0.239 mol) of pulverized potassium carbonate, 5.16 g (15.9 mmol) of tris(3,6-dioxahepyl)amine in 900 mL of toluene was stirred under Ar at reflux for 6 h and then at room temperature overnight. The mixture was poured into 300 mL of water and the organic phase was separated, washed with brine, dried and evaporated to give 84.3 g of methyl (R,S)-6-acetyl-7-[5-(4-acetyl-3-hydroxy-2-propylphenoxy)pentoxy]-3,4-dihydro-2H-l-benzopyran-2-carboxilate. Crystallization from MeOH (0°C, 18 h) gave 66 g (81% yield), m.p. 77-80°C. 

A stirred solution of 55.82 g (0.109 mol) of methyl (R,S)-6-acetyl-7-[5-(4-acetyl-3-hydroxy-2-propylphenoxy)pentoxy]-3,4-dihydro-2H-l-benzopyran-2-carboxylate in 725 mL of MeOH was treated with 4.45 g (0.111 mol) of NaOH in 20 mL of water and the mixture was stirred at reflux for 1.25 h. It was cooled, concentrated to a volume of ca 360 mL, diluted with 310 mL of ether and left at 0°C overnight. The product was collected by filtration, dried in to give 45.76 g of (R,S)-6-acetyl-7-[[5-(4-acetyl-3-hydroxy-2-propylphenoxy)pentyl]oxy]-3,4-dihydro-2H-H-benzopyran-2-carboxylic acid sodium salt (Ablukast) as the monohydrate. A further 12.27 g of product was obtained from the mother liquor to give a total yield of 99%. 

Chemical Name 1,3-Propanediamine, N-((3,4-dihydro-2H-l-benzopyran-2-yl)methyl)-N,-(l,4,5,6-tetrahydro-2-pyrimidinyl)-, dihydrochloride, (2R)-... 

To a stirred and heated +80°C mixture of 3,4-dihydro-2H-l-benzopyran-2-carboxylic acid and methylbenzene were added dropwise thionyl chloride during a period of 85 min. Upon complete addition, stirring was continued for 2 h at 80°C. After cooling to room temperature, the reaction mixture was evaporated. The residue was taken up in methylbenzene and the solvent was evaporated again, yielding (R)-3,4-dihydro-2H-l-benzopyran-2-carbonyl chloride. 

A mixture of 20.0 g (-)-(R)-3-[[(3,4-dihydro-2H-l-benzopyran-2-yl)methyl]amino]propanenitrile and 300 ml of methanol was hydrogenated in the presence of 5.0 g of Raney Nickel. After the calculated amount of hydrogen was taken up, the catalyst was filtered off and the filtrate was evaporated, yielding 21.0 g (100%) of (-)-(R)-N-[(3,4-dihydro-2H-l-benzopyran-2-yl)methyl]-l,3-propanediamine as crude residue. 

CN. [2R [R [R (S )n]-a,a -[iminobis(methylene)]bis[6-fluoro-3,4-dihydro-2H-l-benzopyran-2-methanoll... 

Zur Herstellung von 2-(2,2-Dimethyl-3,4-dihydro-2H-l-benzopyran-8-yl)- (78% Schmp. 127-128°) und 2-(6-CMor-2,2-dimethyI-3,4-dihydro-2H-l-benzopyran-8-yl)-l,3-benzothiazol (Schmp. 146-147°) s.Lit.189 ... 

Methyl-l,4(2H,3H)-phthalazinedione (33) with the epoxide, 2,2-dimethyl-la, 7b-dihydro-2H-oxireno[c][l]benzopyran-6-carbonitrile (33a), gave 4-(6-cyano-3-hydroxy-2,2-dimethyl-3,4-dihydro-27/-[l]benzopyran-4-yloxy)-2-methyl-l(2i7)-phthalazinone (34) (pyridine, EtOH, reflux, 14 h 20%)." ... 

---