5.6.7.8- Tetrahydrobenzo pyrans

When malononitrile was utilized, due to its higher acidity (pA 11.5) with respect to dimedone (pAa 12.0), the reaction could be carried out in a three-component manner by adding the reagents all at once the corresponding tetrahydrobenzo[ ]pyrans were isolated in 77-99% yield. 

Tetrahydrobenzo[ ]pyrans exhibit many important biological and pharmacological properties. Hosseini-Sarvari and Shaflee-Haghighi (2012) documented the synthesis of tetrahydrobenzo[ ]pyrans (81) by one-pot three-component reaction of arylaldehydes (15), active methylene compounds (79), and 1,3-diketones (80) in the presence of nano-ZnO in an aqueous medium (Scheme 9.23). 

S. Balalaie, M. Baraijanian, A. M. Amani, B. Movassagh, Synlett 2006, 263-266. (S)-Proline as a neutral and efficient catalyst for the one-pot synthesis of tetrahydrobenzo[ ]pyran derivatives in aqueous media. 

The bark acids obtained from the various parts of Calophyllum species (Gut-tiferae) possess mostly a phloroglucinol ring system (106). An acid with a very complex structure, carozeylanic acid (126) (gum, [a]o +12.6°), was found in the bark of C. lankaensis (= C. zeylanicum), C. thwaitesii, and C. walkeri (105, 106). This acid composes nearly 80% of the acid fraction in each case. The structure of carozeylanic acid is (2/ ,3/ )-2,3-dimethyl-5-hydroxy-6-(3-methylbutyl)-6-(3,7-dimethyl-octa-3,6-dienyl)-8-(2-carboxyl-l-phenylethyl)-2,3,6,7-tetrahydrobenzo-pyran-4,7-dione (126), a cyclohexadienone system fused to a 2,3-dimethylchro-mone ring. 

A one-pot synthesis of highly functionalized tetrahydrobenzo pyrans has also been reported by Devi and Bhuyan (2004) via sodium bromide catalyzed cyclocondensation of aryl aldehydes, aliphatic nitriles, and dimedone imder solvent-free microwave irradiation conditions. It was observed that the activity of cyanoacetamide is poor as compared to malononitrile and ethyl cyanoacetate. 

A novel mycotoxin, diplosporin, is produced by a toxigenic strain of Dip-lodia macrospora Earle, a fungus isolated from Zambian corn (Chalmers et ai, 1978). The structure 50 [(5S,630-6-ethyl-5-hydroxy-3-hydroxymethyl-5,6,7,8-tetrahydrobenzo[/ ]pyran-4-one] was assigned to this metabolite on the basis of physicochemical data and especially and NMR data. 

Starting from l.l-dichloro-7b-ethoxy-2-methyl-1,1 a,2,7-tetrahydrobenzo[/)]cyclopropa[prepared from the corresponding benzothiopyran by addition of dichlorocarbene, the three 1-benzothiepins 6a-c are formed upon treatment with strong bases, i.e. sodium methoxide or ethoxide in dimethyl sulfoxide.73 The optimal yield of each 1-benzo-thiepin compound depends on the molar equivalents of base, as follows from different ring-opening mechanisms. 

R = CN, C02Et, CONH2 Scheme 6.245 Multicomponent condensation in the synthesis of tetrahydrobenzo[b]pyrans. 

Ranu BC, Banejee S, Roy S (2008) A task specific ionic liquid, [bmim][OH]-promoted efficient, green and one-pot synthesis of tetrahydrobenzo[i)]pyran derivatives. Indian J Chem 47B 1108-1112... 

A range of tetrahydrobenzo[f>]pyrans were synthesized in good yields under solvent-free conditions by grinding a-cyanocinnamonitriles or /i-cyano-/i-carbethoxy styrene and 1 in the presence of TEBA (06SC2363). 

Michael addition of 1 to dimethyl acetylene dicarboxylate in the presence of sodium methoxide, potassium fluoride, or aluminum trioxide gave 435 (R = Me) via an intermolecular cyclocondensation (89MI87). Regioselective cycloaddition of propargylic alcohol and dimedone in the presence of thiolate-bridged diruthenium complex afforded the tetrahydrobenzo[fr]pyran 451 (04JOC3408). 

Reaction of N-methyl-2-pyrrolidine diethylacetal with 2-aminomethy-lene-dimedone 457 (R = Rr = H or Me) afforded the dienediamine 459, which on heating in dilute hydrochloric acid gave 7,7-dimethyl-3-(/ -methylamino)ethyl-5,6,7,8-tetrahydrobenzo[t>]pyran-2,5-diones 460 (87KGS1477). 

Sodium bromide-catalyzed three-component cydocondensation of aryl aldehydes, alkylnitriles, and dimedone to give excellent yields of tetrahydrobenzo[b]pyrans [209]. 

Hosseini-Sarvari, M. and Shafiee-Haghighi, S. 2012. Nano-ZnO as heterogeneous catalyst for three-component one-pot synthesis of tetrahydrobenzo[b]pyrans in water. Chem. Hetero. Comp. 48 1307-1313. 

A variety of tetrahydrobenzo[(i]pyran derivatives (9) were synthesized in good yields via three-component condensation reaction between aryl/alkyl aldehydes, malononitrile, and dimedone in ethanol-water media using both homogeneous and heterogeneous catalysts (Scheme 26) [125,128-131],... 

SCHEME 26 Synthesis of tetrahydrobenzo[fc]pyran derivatives 9 in ethanol-water media [125,128-131]. 

S.B. Bandgar, B.P. Bandgar, B.L. Korbad, J.V. Totre, S. Patil, Uncatalyzed reactions in aqueous media three-component, one-pot, clean synthesis of tetrahydrobenzo[fc]pyran derivatives, Aust. J. Chem. 60 (2007) 305-307. 

A. Mobinikhaledi, M.A.B. Fard, Tetrabutylammonium bromide in water as a green media for the synthesis of pyrano[2,3-d]pyrimidinone and tetrahydrobenzo[6]pyran derivatives, Acta Chim. Slov. 57 (2010) 931-935. 

D. Tahmassebi, J. A. Bryson, S.l. Binz, l,4 Diazabicyclo[2.2.2]octane as an efficient catalyst for a clean, one-pot synthesis of tetrahydrobenzo[fc] pyran derivatives via multicomponent reaction in aqueous media, Synth. Commun. 41 (2011) 2701-2711. 

A. Davoodnia, S. AUameh, S. FazH, N. TavakoH-Hoseini, One-pot synthesis of 2-amino-3-cyano-4-arylsubstituted tetrahydrobenzo[b]pyrans catalysed by silica gel-supported polyphosphoric acid (PPA-Si02) as an efficient and reusable catalyst, Chem. Pap. Slovak Acad. Sci 65 (2011) 714-720. 

A. Mobinikhaledi, N. Foroughifar, M.A.B. Fard, Eco-friendly and efficient synthesis of pyrano[2,3-d] pyrimidinone and tetrahydrobenzo[i ] pyran derivatives in water, Synth. React. Inorg. Met.-Org. Nano-metal Chem. 40 (2010) 179-185. 

H.A. Oskooie, M.M. Heravi, N. Karimi, M.E. Zadeh, Caro s acid-sflica gel an efficient and versatile catalyst for the one-pot synthesis of tetrahydrobenzo[fc]pyran derivatives, Synth. Commun. 41 (2011) 436-440. 

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