Of benzopyrans

Nabitan (39) is a cannabis-inspired analgesic whose nitrogen atom was introduced in order to improve water solubility and perhaps to affect the pharmacological profile as well. The phenolic hydroxyl of benzopyran synthon is esterified with 4-(l-piperidino)butyric acid under the influence of dicyclohexyl carbodi mi de. In addition to being hypotensive and... 

Jones, R. M. Selenski, C. Pettus, T. R. R. Rapid syntheses of benzopyrans from o-OBOC salicylaldehydes and salicyl alcohols a three-component reaction. J. Org. Chem. 2002,67, 6911-6915. 

Over the years, many spiropyran structures have been prepared. The pyran component consists of benzopyran or naphthopyran and the heterocyclic part consists of indoline, benzothiazoline, benzoxazoline, benzoselen-azoline, phenanthridine, acridine, quinoline, benzopyran, naphthopyran, xanthene, benzodithiole, benzoxathiole, and saturated heterocyclic rings such as pyrolidine and thiazolidine. 

Application of an organocatalytic domino Michael addition/intramolecular aldol condensation to the preparation of a series of important heterocycles has recently received much attention [158] with methods being disclosed for the preparation of benzopyrans [159-161], thiochromenes [162-164] and dihydroquinolidines [165, 166]. The reports all use similar conditions and the independent discovery of each of these reactions shows the robust nature of the central concept. A generalised catalytic cycle which defines the principles of these reports is outlined in Fig. 10. Formation of iminium ion 102 is followed by an intermolecular Michael addition of an oxygen, sulfur or nitrogen based nucleophile (103) to give an intermediate... 

Nicolaou, K.C. Pfefferkom, J.A. Barluenga, S. Roecker, A.J. Cao, G.-Q. (2000C) Natural product-like combinatorial libraries based on privileged structures. 3. The libraries from libraries principle for diversity enhancement of benzopyran libraries. J. Am. Chem. Soc., 122, 968-76. 

Analysis of the stems of Encella ventorum from Baja California showed the presence of a number of benzopyran and benzofuran derivatives and two stereo Isomers of a novel euparln-encecalln (XII) dimer (25). A closely related euparln-encecalln dimer (XIII), was previously Isolated from farlnosa (26). Although the dimer Is not photoactive, preliminary studies Indicate that It Is a feeding deterrent to Hellothls zea. 

The synthetic strategies used for the preparation of pyrans on insoluble supports have mainly been hetero-Diels-Alder reactions of enones with enol ethers and ringclosing olefin metathesis (Table 15.33). Benzopyrans have been prepared by hetero-Diels-Alder reactions of polystyrene-bound o-quinodimethanes with aldehydes. The required quinodimethanes were generated by thermolysis of benzocyclobutanes, which were prepared in solution [308]. Other solid-phase procedures for the preparation of benzopyrans are the palladium-mediated reaction of support-bound 2-iodo-phenols with 1,4-dienes (Entry 5, Table 15.33) and the intramolecular Knoevenagel... 

A household microwave oven operating at 2450 MHz was used at its full power, 650 W. A neat mixture of benzopyran derivative 1 or 3 (1 mmol) and hydrazine (1.2-3 mmol) in a 10-mL glass beaker was thoroughly mixed for about 5 min, then it was placed in an alumina bath inside the household microwave oven and irradiated. Maximum temperature reached in the alumina after 10 min was about 150 °C. After cooling, methanol (ca. 4 mL) was added to the mixture and the separated solid was filtered off and washed with a small amount of methanol to give the products 2 and 4. 

In order to meet the objective of a completely tissue-specific antiestrogen, a long series of benzopyran derivatives was synthesized with... 

The palladium(n) catalyzed cyclization of ortho-allylic phenols can lead to a mixture of benzopyran and benzofuran products. The palladium(ll) catalyzed cyclization of ortho-allylic phenols, which bear a variety of substituents on both the aryl ring and the allyl group, in the presence of KHCO3 in DMSO-water (9 1) affords 2//-chromenes exclusively (Equation 15) <1998SL522>. Lower yields of 2//-chromenes are obtained when electron-withdrawing groups are... 

His research interests include the chemistry of benzopyrans and benzothiopyrans and various aspects of color chemistry. These have resulted in the development of a range of photochromic naphthopyrans which are in commercial use in ophthalmic lenses, security materials, and novelty items. 

Nicolaou KC, Pfefferkorn JA, Cao GQ, Selenium-based solid-phase synthesis of benzopyrans. I Applications to combinatorial synthesis of natural products, Angew. Chem., Int., Ed. Engl., 39 743-739, 2000. 

Analogous reactions have been performed in similar benzo- and naphthopy-rane series [101]. Oxidation of benzopyrane derivatives YIII/174 with chromic acid/acetic acid, chromic acid anhydride/acetic acid anhydride, Jones reagent, or ozone gave only complex mixtures of products. Only raefa-chloroperoxyben-zoic acid in dichloromethane was successful (VIII/175 as naphthoketolactones with n = 4, 5, 6 in 70, 49, and 60% yield). 

Fig. 139. Synthesis of benzopyrans and benzoxazincs from phenolic Mannich bases.

In addition to the widely reported techniques of amide bond formation, transesterification, and hydrolysis, enzymic enantioselective oxidation is also used in the synthesis of single isomer drugs. Patel described the elficient oxidation of benzopyran (75), an intermediate in thesynthesisof potassium channel openers (123). The transformationwas ef-fected w i t h a cell suspension of MortiereUa raman-niana with glucose over a 48-h period, the isolated product (77) was obtained in a 76%yield with an optical purity of 97%and a chemical purity of 98%, as shown in Pig. 18.32. 

Nicolaou, K C, Pfefferkom, J A, Cao, G-Q, Selenium-based soUd-phase synthesis of benzopyrans I applications to combinatorial s3mthesis of natural products, Angew. Chem. Int. Ed., 39, 734-739, 2000. 

Nicholas reaction. The intramolecular version has been applied to the synthesis of benzopyran system. ... 

Figure 8. Assumed partial reaction profile for the enantiomerizations of benzopyrans and benzo-1,4 oxazines. D is an electron-donating group. R is methyl or hydrogen or forms a second heterocyclic ring with D. X = CH, N. The two transition states are symbolized by only one of the possible resonance formulas in both cases, i.e., the charges drawn are not localized.

Remarks Pertaining to All Types of Benzopyrans and Benzo- 1,4-oxazines... 

The titled reactions are employed for synthesis of benzopyrane derivatives. Thus, the racemic cordiachromene 202 (from the cannabinoid class) was prepared starting from 6-methylhept-5-en-2-one 200 using the Claisen rearrangement of the intermediate propargyl ether 201 in an overall yield of 50% (equation 93) . 

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