Reissert salts

This French group (145) has also been able to divert the usual Diels-Alder cycloaddition pathway of Reissert salts with oleftnic esters to a 1,3-dipolar cycloaddition pathway by the addition of triethylamine. In addition, mtinchnone imine 243 can be trapped with dipolarophiles to furnish 244 (146). No Diels-Alder cycloadducts derived from the oxazolium salt were detected. In contrast, fumarate... 

Benzoyl-1,2-dihydro-1-cyanoisoquinoline was treated with fluoro-boric acid in glacial acetic acid to give the Reissert salt 56 reactions of the latter with EPP, DMAD, and ethyl tetrolate were examined. With EPP, the initial bridged compound 58 was isolated as a moderately stable crystalline compound, and was the first example of an isolated... 

Reactions of quinoline Reissert compounds were less satisfactory than those of the corresponding isoquinolines. The hydrochloride of 64 with DMAD gave 65 in only 7% yield in methylene chloride ethanol, and 10% in DMF. From a study of the mechanism of the 1,3-dipolar addition of Reissert salts to arylpropiolate esters, McEwen et a/.499 concluded that a concerted cyclization was more probable than a two-step process. 

Azine approach. Reissert compounds such as (222) on treatment with acid form transient cyclic intermediates containing the 3,4-fused oxazole ring. When the acid is tetrafluoroboric acid, the Reissert salt (223) can be isolated (73JA2392). 

Several stable Reissert salts (19 X = CIOJ have been reported, " and reactions with alkynes and alkenes have been studied. 

In summary, it appears that Reissert salts undergo 1,3-dipoIar addition reactions with reactive acetylenic 1,3-dipolarophiles to give compounds of type 24 and undergo complex condensation-rearrangement reactions with olefinic dienophiles to give products of the type 25. 

Many of the papers dealing with the synthesis and reactions of Reissert compounds routinely include spectral data. These data are consistent with the structures assigned and with previously reported spectral data for Reissert compounds. It should be noted that comparisons of data of this type was used to assign the structures 4 and 5, which were assigned to the Reissert compounds from 1,7- ° and 1,6-naphthyridine. A detailed spectral study of Reissert salts led to the assignment of structure 19. 

Treatment of the compounds 78 with various alkyl halides in the presence of sodium hydride results in 1-alkylation as with normal Reissert com-pounds. ° Acylation has also been reported under these conditions. Under a variety of conditions, however, 78 does not react with benzaldehyde. Acid hydrolysis of 80 gave tetrahydroquinaldic acid, while acid hydrolysis of the alkylated dihydroisoquinoline-Reissert compounds gave the amino acids 81. By first complexing the alkylated dihydroisoquinoline-Reissert compound with zinc chloride in ether and then hydrolyzing the complex, the nitrile was hydrolyzed to an acid, but the amide group was left intact. The perchlorate salts of dihydroisoquinoline-Reissert compounds have also been prepared, and sodium borohydride reduction proceeds in the same manner as reduction of the Reissert salt to... 

A Reissert compound has been prepared from 9-methoxyellipticine and both it and 10 give a fluoroborate salt of the type 19. The Reissert compound of 6,7-dimethoxyphthalazine has been used to prepare an azapa-paverine. The oxoaporphine alkaloid subsessiline has been synthesized using the Reissert compound of 5,6,7-trimethoxyisoquinoline. The reaction of vanillin Schiff bases with benzoyl cyanide yields open-chain analogs of Reissert compounds. a-Acylaminonitriles, which can be considered as open-chain Reissert compounds, have been converted to open-chain analogs of Reissert salts (5-imino-3,5-dihydrooxazole derivatives). - ... 

Nucleophilic addition of 1005 to an 7V-acyliminium ion, e.g., a Reissert salt, and oxidation of the resulting adduct affords a 2-(heteroaryl)oxazole 1019. Acylation of a nitrogen heterocycle 1016 with ethyl chloroformate generated the intermediate Reissert salts 1017 in situ (Scheme 1.272). Addition of 1005 to 1017 gave adducts 1018, which produced 1019 after oxidative deacylation with o-chloranil. Examples of 2-(heteroaryl)oxazoles prepared from thiazole, benzothia-zole, pyridine, quinoline, and isoquinoUne are shown in Table 1.77. Donodni and co-workers summarized their early work on preparation and reaction of 2-(trimethylstannyl)oxazoles and 2-(trimethylsilyl)oxazoles. 

Iyer and co-workers invoked the presence of an open-chain bis-Reissert salt to explain the facile conversion of 1049 to 1051 (Scheme 1.279). Thus cyclization of 1049 with perchloric acid generated the bis-oxazoUum perchlorate 1050, which was isolated and completely characterized spectroscopically. The predominant tautomer in solution was 1050, based on H NMR. Hydrolysis of 1050 then produced the bis amino acid 1051, a known metabolite of the antitubercular drug ethambutol, 1052. ... 

This group " also diverted the usual Diels-Alder cycloaddition pathway of Reissert salts with olefinic esters to a 1,3-dipolar cycloaddition pathway by the addition of triethylamine. Thus treatment of munchnone imine 364 with ethyl acrylate and triethylamine affords the 1,3-dipolar cycloaddition product 366 (30%) as the major product, formed by fragmentation of cycloadduct 365 (Fig. 4.121). The Diels-Alder product (not shown) is formed in 15% yield. Similar products to 366 are formed with dimethyl and diethyl maleate and fumarate. Laude and coworkers " also were able to trap munchnone imine 367 with dipolarophiles to furnish 368 (Fig. 4.122). No Diels-Alder cycloadducts derived from the oxazolium salt were detected. In contrast, fumarate and acrylate esters give only Diels-Alder cycloadducts from the tautomeric oxazolium salt (not shown). However, benzo-quinones and 1,4-naphthoquinone react in a 1,3-dipolar fashion with munchnone imine 372 derived from Reissert compound 369 to give 373 (Scheme 4.11). " Diels-Alder cycloadducts derived from oxazolium salt 371 were not observed. In a... 

TABLE 1.77 2-(HETEROARYL)OXAZOLES FROM 4-METHYL-2-(TRIMETHYLSILYL) OXAZOLE AND REISSERT SALTS, 226... 

---