277- Benzopyran-3-carboxaldehydes

A mixture of 2 ml of morpholine, 3 ml of dimethylformamide and 10 ml of water was heated to 60°C and under stirring the equal molecular quantity of 6-isopropyl-4-oxo-4H-l-benzopyran-3-carbonitrile was added for 5 minutes. The mixture was heated at that temperature for one hour and the resultant precipitate was filtered, rained with water recrystallized from acetic acid and washed with chloroform. By the above procedure was obtained 2-amino-6-isopropyl-4-oxo-4H-l-benzopyran-3-carboxaldehyde melting at 206°-208°C. A mixture of 4 ml ethyl cyanoacetate, 50 ml of ethanol, 5 ml of piperidine and the equal molecular quantity of 2-amino-6-isopropyl-4-oxo-4H-l-benzopyran-3-carboxaldehyde was refluxed for 30 minutes and, after cooling, the crystalline precipitate was filtered and washed with chloroform. By above procedure was obtained ethyl-2-amino-7-isopropyl-l-azaxanthone-3-carboxylate, melting after recrystallization from ethanol at 243°-244°C. A mixture of 10 ml of acetic acid and 10 ml of 55% sulfuric acid the equal molecular quantity and 2-ethyl-amino-7-isopropyl-l-azaxanthone-3-carboxylate was stirred at 130°C for 4 hours and, after water was added, the precipitate was collected by filtration and recrystalllized from dimethylformamide to give the 2-amino-7-(l-methylethyl)-5-oxo-5H-[l]benzopyrano[2,3-b]pyridine-3-carboxylic acid, melting point 300°C. 

El-Shaaer, H., Foltinova, R, Lacova, M., Chovancova, J., and Stankovicova, H. 1998. Synthesis, antimicrobial activity and bleaching effect of some reaction products of 4-oxo-4//-benzopyran-3-carboxaldehydes with aminobenzothiazoles and hydrazides. II Farmaco, 53 224-32. 

The reaction of salicylaldehydes with a,P-unsaturated aldehydes in aqueous dioxane and under sonification affords a mixture of 2//-[l]benzopyran-3-carboxaldehydes and a tricyclic hemiacetal. The former is considered to arise from the 1,4-addition of a phenolate ion and the latter by a vinylogons aldol reaction. The choice of base controls the relative amounts of the two products, with Na2C03 favouring the chromene and NEts the chroman. <05ASC555>. 

Treatment of 4-(l-aryl-l-hydroxymethyl)-2,2-dimethylchromenes with PBrs at 0 °C produces the 4-arylidenechroman e.g. 13 <05TL8849>. The cannabinoid ring system has been obtained from 27f-[l]benzopyran-3-carboxaldehydes by conversion to the 3-vinyl derivative and a subsequent thermal DA reaction with methyl vinyl ketone <0581888>. 

The Sommelet reaction has been widely extended to heterocycles, which are important to medicinal chemists. With yields ranging from 50% to 57%, aldehydes of pyridine, isoquinoline, and thiazole were prepared from the corresponding heteroarylmethyl bromides.27 5-Benzyloxy-3-bromomethyl-benzo[i]thiophene (30) was converted to 3-carboxaldehyde 31 in 40% yield.28 Thiazole 32 was the core structure in another Sommelet reaction to give 33 although in poor yield.29 In contrast, a different thiazole substrate 34 gave aldehyde 35 in 49% yield.30 Benzopyrans are also tolerated by the Sommelet reaction conditions.31,32 For example, substrate 36 was converted to aldehyde 37 in 58% yield.32... 

Oxo-4//-l-benzopyran 3-carboxaldehyde (Use of Pyrophosphoryl Chloride) 2-Bromocyclohex-l-ene-l-carboxaldehyde (Use of PBr to Produce a 2-Bromoenal)... 

Oxo-4H-l-benzopyran-3-carboxaldehyde (Use of Pyrophosphoryl Chloride). To a stirred solution of o-hydroxyacetophenone (25 g, 0.184 mol) in 80 mL of DMF, 80 mL of (Cl2P0)20 was added dropwise at —20° during about 10 minutes. The mixture was stirred at room temperature for 13 hours, and decomposed by ice-water. The resulting precipitate was collected by filtration, washed with H2O and then EtOH, and recrystallized from acetone to afford the benzopyrancarboxaldehyde (19.6 g, 61%) as colorless crystals, mp 152-153° (lit. 152°). From the ethanol washings a small amount (430 mg) of tranr.A (2-hydroxybenzoyl) 2-(4-oxo-4//-l-benzopyran-3-yl)ethylene, mp 177-179° (from acetone) was isolated. 

An earlier investigation (23) demonstrated that the Vilsmeier-Haack reaction of the ArCOCHj type compounds gives the monoformylated compounds or the corresponding P-chloro-vinyl aldehydes. It was found, however, that in the case of o-hydroxyacetophenones, the methyl group was doubly formyl-ated by a Vilsmeier reagent to give our first target compounds, 4-oxo-4H-l-benzopyran-3-carboxaldehydes ( ) in one step ( 1, J ). The reason why double formylation took... 

The second target, 4-oxo-4H-l-benzopyran-3-carboxylic acids (3) were obtained by Jones oxidation of or hydrolysis of the 3-carbonitrile derivatives ( ) described below (14). The third target, 3-(4-oxo-4H-1-benzopyran-3)acrylic acids (4) were synthesized generally by the Knoevenagel reaction of 3-carboxaldehydes (2) with malonic acid ( 1 ). In the meantime, it was found that the 3-carboxaldehydes ( ), which were able to function as P-dialdehyde compounds, were attacked by amide groups in some cases, to give 2(IH)-pyridone derivatives after condensation with malonic acid derivatives. Thus, condensation of 2 with malonodiamide in pyridine gave initially acrylamide derivatives which were converted into 3-carbamoyl-5-(2-hydroxybenzoyl)-2(IH)-pyridones ( ) (24) ... 

Ng bubbled overnight through acrolein and then through a fritted disk into a mixture of salicylaldehyde and aq. NaOH 2H-l-benzopyran-3-carboxaldehyde. Y 85%. - Similarly with methyl vinyl ketone 3-acetyl-2H-l-benzopyran. Y 72%. F. e. s. CD. deBoer, J. Org. Chem. 59, 2426 (1974). 

Dihydro-5,7-dihydroxy-8-methyl-4-oxo-2-pheny 1-4//-1 -benzopyran-6-carboxaldehyde,... 

Dihydro-2,5,7-trihydroxy-6-methyl-4-oxo-2-phenyl-2i/-benzopyran-8-carboxaldehyde, see F-20027... 

Obtained (17% yield) by adding a solution of 4-OXO-4)/-1 -benzopyran-3-carboxaldehyde in acetic acid to a preheated (70-80°) mixture of acetylacetone in acetic acid containing a catalytic amount of concentrated hydrochloric acid [5949]. 

The enantioselective intramolecular formal 2+4-cycloaddition of acrylates and a, -unsaturated imines (99) catalysed by chiral phosphines (100), derived from amino acids, produced A-heterocycles (101) (Scheme 31). Chiral dirhodium(II) carboxamidates (102) catalysed the hetero-Diels-Alder reactions between 2-aza-3-silyloxy-l,3-butadienes and aldehydes to yield all cw-substituted l,3-oxazinan-4-ones in high yields and high enantioselectivity (98% ee)P The nickel-catalysed 4 + 2-cycloaddition of a, -unsaturated oximes with alkynes yielded 2,3,4,6-tetrasubstituted pyridine derivatives. The reaction of isoquinoline, an activated alkyne, and 4-oxo-4//-l-benzopyran-3-carboxaldehyde (103), in ionic solvents, produced 9a//,15//-benzo[a][l]benzopyrano[2,3-/t]quinolizine derivatives (105) via the zwitterion (104) selectively and in good yields (Scheme 32).The Diels-Alder cycloaddition of ethyl 3-(tetrazol-5-yl)-l,2-diaza-l,3-butadiene-l-carboxylates with -rich heterocycles, nucleophilic olefins, and cumulenes formed 3-tetrazolyl-l,4,5,6-tetrahydropyridazines regioselectively. The silver-catalysed formal inverse-electron-demand Diels-Alder... 

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