Benzopyranes 622 Subject

Despite these challenges, the area of K+ channel openers (PCOs) is emerging as an active area of drug design. Over the past 5-10 years, eight novel structural classes of PCOs have received systematic development benzopyrans (e.g., cromakalim, 7.27), cyanoguanidines (e.g., pinacidil, 7.28), thioformamides (e.g., aprikalim, 7.29), pyridyl nitrates (e.g., nicorandil, 7.30), benzothiadiazines (e.g., diazoxide, 7.31), pyrimidine sulphates (e.g., minoxidil sulphate, 7.32), tertiary carbinols, and dihydropyridines. These various classes have been subjected to analog preparation with compound optimization via structure-activity studies. 

We also discovered the ability of 2-azadienes of this sort to cycloadd to unactivated carbon—carbon double and triple bonds in an intramolecular fashion (89CC267) (Scheme 50) such a process appears to be one of the first examples of intramolecular [4 + 2] cycloadditions of simple 2-azadienes. Azadiene 216 was made from O-allyl salicylaldehyde 215 (R = allyl) and heated at 120°C in toluene to furnish the trans-fused tricyclic adduct 217 in excellent yield further dehydrogenation of 217 with DDQ afforded 5H-[ 1 ]-benzopyran[4,3-6]pyridine 218. On the other hand, when 0-(2-butynyl) salicylaldehyde 215 (R = 2-butynyl) was transformed into azadiene 219 and subjected to heating in a sealed tube at 150°C, pyridine 222 was isolated in very high yield. Its formation can be rationalized to occur via the expected Diels-Alder intermediate 220 thus, [1,5]-H shift in 220 would give rise to tautomer 221, which would suffer electro-cyclic ring-opening and aromatization to pyridine derivative 222. 

The aim of this review is to survey the advances in the chemistry of chrom-3-enes (2//-l-benzopyrans, chrom-/l -enes, a-chromenes) in the last decade. This subject was previously summarized by Wawzonek in 1951. A brief but clear treatment of chrom-3-ene chemistry can be found in Dean s book (1963), where a detailed account is given of all the natural products known at that time. A section of a recent book on the synthesis of natural compounds has been dedicated to chromenes. The present review will not deal with chrom-2-enes, nor with benzo-pyrylium salts, nor with ring-fused pyrano-heterocycles. The reader... 

A solution of 4-(dimethoxyphosphoryldiazomethyl)-3-phenyl-4/f-benzopyran (0.356 g, 1 mmol) and -al-lylchloropalladium dimer (15 mg, 0.04 mmol) in benzene (50 mL) was stirred at rt for 18 h. The reaction mixture was then concentrated at 30 °C under vacuum (15 Torr), and the oily residue was subjected to flash column chromatography (EtjO). Crystallization [EtjO/petroleum ether (bp 30 75°C)] afforded the title compound as colorless crystals yield 0.3 g (91%) mp 120°C. 

Conjugate addition products 322 and 323 have been subjected to hydro-genolysis in the presence of 10% Pd/C catalyst (Scheme 4.103). " 3-Substituted coumarins 324 were obtained in 50-66% yields from substrates 322 through fission of the benzyl ether and spontaneous cyclization via acyl substitution. Using compounds 323 as substrates, piperidinyl derivatives 325 were obtained in 45-61% yields, and the de-aminated derivatives 326 were also acquired in 9-21% yields. Such a synthetic method may enable the synthesis of multi-substituted coumarins (2//-l-benzopyran-2-ones), which are widely distributed in nature and many of which exhibit pharmacological activities. 

Enynylphosphine oxides were prepared and then subjected to carbocu-pration reactions to give dienylphosphine oxides, as shown in Scheme 29 Arylhydrazono-alkylphosphine oxides were converted to the corresponding azoalkene derivatives on treatment with iodic acid (Scheme 30). Otherwise unreactive chloroarylphosphine oxides have been shown to undergo Suzuki coupling on MW irradiation in the presence of a highly active palladium-catalyst (Scheme 31 Treatment of 2-fluoro-5-nitrobenzyl bromide with active methylene compounds, such as a p-keto phosphine oxide under suitable conditions led to 4/7-1-benzopyrans (Scheme 32)." ... 

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