2-Chroman

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 

NMR examination shows that the chroman system exists in a half-chair conformation. 

Reactions with electrophiles, e.g. SgAr processes, occur on the benzene moiety on C-6 as expected. 2,2-Disubstituted chroman-4-ones undergo ring opening by attack of alkali hydroxide on C-2 and formation of a, p-unsaturated o-hydroxyphenyl ketones 3. Acids bring about recyclization. Flavanones are ring opened by traces of alkali. 

Isochroman 1 undergoes substitution and ring-opening, provided suitable leaving groups are present on the reactive C-1 benzyl position. The transformations of the 1-bromo compound 4, which involve the carboxonium ion 5, serves as a characteristic example [40]  

The synthesis of chromans is possible according to several routes. 

Pyronine G (31) is obtained by the oxidation of the leuco compound 32 in acid medium 32 results from acid-catalyzed cyclocondensation of 3-dimethylaminophenol with formaldehyde  

Rotenone (33), the toxic principle from the roots of denis ediptica, is a natural insecticide. Its structure shows a unique combination of berrzarmulated dihydropyran, dihydro-4-pyrone, and dihydrofuran ring systems [69]. 

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It may be regarded as the parent of a number of important classes of compounds derived from the y-pyrone skeleton (e.g. flavone, xan-thone) and the important chroman derivatives called the tocopherols (vitamin E). 

Cycloaddition of COj with the dimethyl-substituted methylenecyclopropane 75 proceeds smoothly above 100 °C under pressure, yielding the five-membered ring lactone 76. The regiocheraistry of this reaction is different from that of above-mentioned diphenyl-substituted methylenecyclopropanes 66 and 67[61], This allylic lactone 76 is another source of trimethylenemethane when it is treated with Pd(0) catalyst coordinated by dppe in refluxing toluene to generate 77, and its reaction with aldehydes or ketones affords the 3-methylenetetrahy-drofuran derivative 78 as expected for this intermediate. Also, the lactone 76 reacts with a, /3-unsaturated carbonyl compounds. The reaction of coumarin (79) with 76 to give the chroman-2-one derivative 80 is an example[62]. 

Another structural type is chromenes. Centchroman [31477-60-8]is a pyrrolidinoethoxyplienyl chromane which is a potent antiestrogen with weak estrogenic activity. In India, it is used as a weekly contraceptive pih based on its reported abiUty to inhibit the uterine preparation for the attachment of the fertilized ova to the wall of the utems (see Contraceptives) (31). 

Cromakalim (137) is a potassium channel activator commonly used as an antihypertensive agent (107). The rationale for the design of cromakalim is based on P-blockers such as propranolol (115) and atenolol (123). Conformational restriction of the propanolamine side chain as observed in the cromakalim chroman nucleus provides compounds with desired antihypertensive activity free of the side effects commonly associated with P-blockers. Enantiomerically pure cromakalim is produced by resolution of the diastereomeric (T)-a-meth5lben2ylcarbamate derivatives. X-ray crystallographic analysis of this diastereomer provides the absolute stereochemistry of cromakalim. Biological activity resides primarily in the (—)-(33, 4R)-enantiomer [94535-50-9] (137) (108). In spontaneously hypertensive rats, the (—)-(33, 4R)-enantiomer, at dosages of 0.3 mg/kg, lowers the systoHc pressure 47%, whereas the (+)-(3R,43)-enantiomer only decreases the systoHc pressure by 14% at a dose of 3.0 mg/kg. 

Derivatives of ubiquiaones are antioxidants for foodstuffs and vitamins (qv) (217,218). Ubichromenol phosphates show antiinflammatory activity (219). Chroman o1 compounds inhibit oxidation of fats and can be used ia treatment of macrocytic anemias (220). Monosulfate salts of 2,3-dimethoxy-5-methyl-6-substitutedhydroquiaone have been reported to be inhibitors of Hpid oxidation ia rats (221). Polymers based on chloranilic and bromanilic acid have been prepared and contain oxygenated quiaones (63), which are derived from 1,2,3,4-benzenetetrol (222). 

Acrylic acid, -(3-benzo[f>]thienyl)-a -mercapto-reaction with iodine, 4, 764 Acrylic acid, o -cyano-y3-(2-thienyl)-ring opening, 4, 807 Acrylic acid, -formyl-in pyridazinone synthesis, 3, 46 Acrylic acid, furyl-rotamers, 4, 545 synthesis, 4, 658 Acrylic acid, 2-hydroxybenzoyl-chroman-4-one synthesis from, 3, 850 Acrylic acid, 5-(l-propynyl)-2-thienyl-methyl ester occurrence, 4, 909 Acrylonitrile... 

H-Benzo[a]carbazole, 4,4a,5,l 1,1 la,l Ib-hexahydro-synthesis, 4, 283 Benzo[b]carbazole, N-acetyl-photochemical rearrangements, 4, 204 Benzo[/]chroman-4-one, 9-hydroxy-2,2-dimethyl-synthesis, 3, 851 Benzochromanones synthesis, 3, 850, 851, 855 Benzochromones synthesis, 3, 821 Benzocinnoline-N-imide ring expansion, 7, 255 Benzocinnolines synthesis, 2, 69, 75 UV, 2, 127 Benzocoumarins synthesis, 3, 810 Benzo[15]crown-5 potassium complex crystal stmcture, 7, 735 sodium complex crystal stmcture, 7, 735 Benzo[ 18]cr own-6 membrane transport and, 7, 756 Benzo[b]cyclohepta[d]furans synthesis, 4, 106 Benzocycloheptathi azoles synthesis, 5, 120... 

Benzofurans, 4, 531-597, 657-712 chroman synthesis from, 3, 785 chromene synthesis from, 3, 753 chromone synthesis from, 3, 828 CNDO, 4, 536... 

Chroman, 6-hydroxy-2,2-dimethyl- C NMR, 3, 587 Chroman, 2-hydroxymethylene-synthesis, 3, 781... 

Chroman, 4-(p-hydroxyphenyl)-2,2,4-trimethyl-X-ray studies, 3, 622 Chroman, 2-methoxy-synthesis, 3, 806 Chroman, 5-methoxy-synthesis, 3, 778 Chroman, 7-methoxy-synthesis, 3, 778 Chroman, 8-methoxy-acylation, 3, 732 Chroman, 2-methoxy-2-methyl-synthesis, 3, 780 Chroman, 2-methyl-synthesis, 3, 785 Chroman, 5-methyl-reactivity, 3, 732 Chroman, 6-nitro-synthesis, 3, 784 Chroman, 4-phenyl-synthesis, 3, 783 Chroman, thio-metabolism, 1, 241 Chroman, 5,6-thio-2-substituted... 

Chroman-2-carboxylic acid, 2-hydroxy-4-oxo-ethyl ester synthesis, 3, 852... 

Chroman-2-carboxylic acid, 6-hydroxy-2,5,7,8-tetramethyl-as antioxidant, 3, 718 oxidation, 3, 725... 

Chroman-4-carboxylic acid, 6,7-dimethoxy-3-oxo-ethyl ester... 

Chroman-6-carboxylic acid, 8-hydroxy-2-methyl-4-0X0—see Rosellinic acid, 718 Chroman-2,7-dicarboxylic acid, 2,4,4-trimethyl-formation, 3, 733... 

Chroman-3,4-diol, 7-methoxy-2,2-dimethyl-conformation, 3, 631 Chroman-3,4-diols IR spectra, 3, 595 Chromanochromanones... 

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