Quinolones, rearrangement

A review of Claisen rearrangements in aqueous solution has appeared. The synthesis of natural products utilizing tandem Diels-Alder additions with sigmatropic rearrangement processes has been reviewed, and a brief review of the regioselective synthesis of coumarins, quinolones and thiocoumarins with 3,4-fused pyran or furan ring systems by the Claisen rearrangement has been presented. ... 

DMAD get thermally converted to quinolones (66), through a Cope rearrangement. These quinolones give rise to tricyclic heteroaromatic compounds, namely, pyrano[3,4-6]quinoline-l,5-diones (67) and furo-[3,2-c]quinolines (68), depending on the reaction conditions (Scheme... 

With malonic acid they form 2-quinolone-4-carboxylic acids (166) by acid-catalyzed rearrangements of intermediates (165). 

A new approach to the synthesis of 4-alkoxy-l-methyl-2-quinolones has been described (Scheme 3).18 Irradiation of 4-alkoxy-2-methylquinoline 1-oxides (12) (prepared from 2-methyl-4-nitroquinoline 1-oxide) results in photo-rearrangement to give the 2-quinolones (13) as major products a mechanism (Scheme 3) has been proposed. The alkaloids (13 R = Me) and ravenine (13 R = CH2CH=CMe2), which have been synthesized by other means, were prepared in this way. 

An interesting and novel rearrangement of quinoline N-oxides was recently discovered. In synthesizing 2-heptyl-l-hydroxy-4(l//)-quinolone, Hammerschmidt et al. observed an unexpected rearrangement of 4-(alkoxycarbonyloxy)quinoline A+oxidcs 116 to 1-(alkoxycarbonyloxy)-2-heptyl-4(l//)-quinolones 117 <07S1517>. 

Rearrangements of allyloxyquinolines were carried out as early as 1924.14 2-Allyloxyquinoline was prepared by reacting 2-chloroquino-line with sodium allyloxide in allyl alcohol. The ether was rearranged by heating it to 325-329°. l-Allyl-2-quinolone was isolated as the product. Even attempted distillation of the starting ether at atmospheric pressure resulted in the formation of the quinolone. The l-allyl-2-... 

In their work on antimalarial compounds, Saltzer et al.4 also effected similar rearrangements. In every instance, the products were assumed to be the corresponding 3-allyl-4-quinolones (see Table II). 

Allyl and crotyl ethers were prepared from 3-propyl-4-quinolones by two different approaches. Displacement of 4-chloro-3-propyl-quinoline by the sodium salt of the two alcohols gave the ethers (1) as clean products, whereas reacting 3-propyl-4-hydroxyquinoline with allyl bromide in the presence of sodium ethoxide afforded not only the allyl ether but also the 1-allylquinolone (2). The products were well-characterized by their ultraviolet spectra and infrared bands. Rearrangement of the ethers at 200° without solvent gave quantitative yields of the corresponding l-allyl-3-propyl-4-quinolones (2). 

Further support for this observation was secured from a study of the rearrangement of the two ethers 3-allyl-4-methallyloxyquinoline and 4-allyloxy-3-methallylquinoline. The quinolone product obtained in quantitative yields in both cases was found by infrared spectral analysis to be a 1 1 mixture of the two possible structures (3 and 4). 

A novel quinolone-ring fused oxepine 56 (n = 1), reported by Joseph et al., was accessed by a ring-closing metathesis reaction on the precursor 55, which was made in turn from 53 via 54, and a Claisen rearrangement on the last compound. An aza analogue of 56 (n = 1) was made in a similar direct approach <03SL2089>. 

Cycloaddition of but-l-yne to the quinolone (58a) gave the head-to-tail [2 + 2] adduct (59). This approach was coupled with a ring-opening reaction to provide a synthesis of quinolones bearing a substituent at C-3. For example, the cycloadduct (60), obtained from the quinolone (58b) and 2-methylbut-3-yn-2-ol, was transformed into edulinine (61). The photocycloaddition of allene to the quinolone (58b) affords the two [2 + 2] adducts (62, 59.6%) and (63, 9.7%). Diketene has also been used in cycloadditions to quinolones (58c) and (58d). The addition process is selective in that cycloaddition to (58c) yields the adduct (64) whereas (58d) affords (65). In the latter case, the cycloadduct is accompanied by the rearranged product (66). These adducts were used in further chemical transformations. 

Rearrangement also occurs when balfourodine is treated with methyl sulfate, isobalfourodine methosulfate being formed. When the alkaloids or the methosulfate are treated with strong alkali, angular dihydrofuro-and dihydropyrano-2-quinolones (LIU, LIV) are formed because of the occurrence of stereochemical inversions in some of these transformations both (-f-)- and (— )-forms of the rearrangement products can be obtained IS). Similarly, Beyerman and Rooda 122) have shown that Lunasia II is isomerized by alkali to LIV. The structures of these i/i-alkaloids were assigned by correlation of the UV-spectra with those of model compounds. 

Under controlled photolytic conditions, the rearranged oxidized product 273 was isolated from acetonitrile solution, and its structure was confirmed by X-ray analysis (Figure 19). Extensive photolysis led eventually to formation of di- and trimethyloxindoles, 13 and 14, a quinolone derivative, 265, and, in the case of spirooxazines, naphthoxazole 268. In the case of the two spiropyrans included in the study, 2-hydroxyl-l-naphthaldehyde and 5-nitrovanillin were also formed. It is... 

Adducts (114) are formed on irradiation of the quinolone (115) with cyclopentene, cyclohexene, and 2,3-dimethylbut-2-ene. Kaneko et al. have studied the addition of diketene to the quinolinone (116) to yield the adduct (117). The rearrangement of the cyclobutanol (118) can be brought about by irradiation in the presence of HgO/12- ... 

Tabernaemontana divaricata (double flower variety) provided an unusual minor alkaloid, voaharine (178), whose structure was established by X-ray analysis [137]. Voaharine is exceptional in being in all probability a tryptamine and jccologanine derived alkaloid but possessing a 3-quinolone instead of an indole chromophore. Voaharine is probably derived from voaphylline (180) (which is also present in the plant) via oxidation and rearrangement and represents the first instance of a 3-quinolone-type alkaloid obtained from Tabernaemontana. Besides these, and the known alkaloids N-methylvoaphylline (181), pachysiphine (tabersonine-P-epoxide) and apparicine, as well as two new bisindoles (vide infra), the plant also provided several new alkaloids of the aspidosperma-type including (-)-mehranine (179), voafinine (182), N-methylvoafinine (183), voafinidine (184) and voalenine (185) which were obtained in minute amounts [138-140]. 

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