Conversion to Other Heterocycles

CHEMICAL REACTIONS Reactions of the carboxyl group Esters formation and reactions Acyl chlorides formation and reactions Decarboxylation Miscellaneous reactions Reactions of the pyrone carbonyl group Reactions of the pyrone ring Reactions of the benzene ring Conversion to other heterocycles... 

The diazotization of amino derivatives of six-membered heteroaromatic ring systems, particularly that of aminopyridines and aminopyridine oxides, was studied in detail by Kalatzis and coworkers. Diazotization of 3-aminopyridine and its derivatives is similar to that of aromatic amines because of the formation of rather stable diazonium ions. 2- and 4-aminopyridines were considered to resist diazotization or to form mainly the corresponding hydroxy compounds. However, Kalatzis (1967 a) showed that true diazotization of these compounds proceeds in a similar way to that of the aromatic amines in 0,5-4.0 m hydrochloric, sulfuric, or perchloric acid, by mixing the solutions with aqueous sodium nitrite at 0 °C. However, the rapidly formed diazonium ion is hydrolyzed very easily within a few minutes (hydroxy-de-diazonia-tion). The diazonium ion must be used immediately after formation, e. g., for a diazo coupling reaction, or must be stabilized as the diazoate by prompt neutralization (after 45 s) to pH 10-11 with sodium hydroxide-borax buffer. All isomeric aminopyridine-1-oxides can be diazotized in the usual way (Kalatzis and Mastrokalos, 1977). The diazotization of 5-aminopyrimidines results in a complex ring opening and conversion into other heterocyclic systems (see Nemeryuk et al., 1985). 

The quaternary salts of selenium-nitrogen heterocycles are labile to nucleophiles and can be converted to other heterocyclic systems by ring expansion [82, 103], An example is conversion of 1,2,4-selenadiazolium trifluoromethane sulfonate (67) into 1,3,5-selenadiazine (68) (Scheme 17) [104], 2,3-Dimethyl-1-benzo-l, 3-selenazolium tetrafluoroborate is readily condensed with aromatic aldehydes to 2-styrylselenazole [105] or treated with sodium hydride to give 3-methyl-2-methylene-2,3 -dihydro-1 -benzo-1,3 -selenazole [106],... 

Many synthetic methodologies have been described for the conversion of isatins to other heterocyclic systems. This chemistry can be generalised as one of the following strategies ... 

Many thiophenes are prepared by processes involving a ring transformation, that is, conversion of other heterocyclic compounds to thiophenes. Several syntheses of this type have already been described however, there are still many syntheses that should be independently treated here. 

The route exploiting nitrile sulfides is used nowadays, affording isothiazoles of type 542 and 543 whose substitution at the 4- and 5-positions depends on the substitution on the dipolarophiles (see Section 4.05.9.2.2). Even the conversion of substituted furans into isothiazoles of type 563 is a known and still topical procedure (see Section 4.05.10.2). A much simpler procedure than the previously reported ones has been described <2001J(P1)1304>, and was applied to a number of macrocyclic isothiazoles <2002CC232> and extended to other heterocycles <1997J(P1)3189, 1997CC1493>. 

Conversion of azlactones to other heterocyclics 1,2,4-Triazines from 4-alkylidene-5-oxazolones... 

Four-membered Ring Nitrogen Heterocycles.— The synthesis of azetidine and its derivatives by akylation of an external or an internal amine is well known, and two more examples were reported in 1980. Interest in simple alkyl substituted azetidines now lies in studies on their stereo-preferences, and conversions to other important systems. That said, two photochemical investigations surprisingly turned up such systems as unexpected major products. Pete et while extending their work on 2-amino-cyclohex-2-enones examined the consequence of N-sulphonylation on their photochemical behaviour, and instead of getting aziridines as the principal products, they obtained azetidines (Scheme 35). These reactions were not as clean as the earlier ones, and aryl migration... 

The reductive alkylation of DAP with acetone led to high conversions and selectivity to the dialkylated product over Al, Bl, and BS2 catalysts. The ASl catalyst, which typically has lower activity than the Al or Pt-based catalysts showed greater formation of heterocycles. These results indicate that a more active catalyst, a shorter reaction time, a higher operating temperature, or sterically hindered amines/ketones will help minimize the formation of the heterocycles. Similar high selectivities were obtained with DAP-MIBK reaction over BSl and BS2 catalysts with no heterocycles being formed. However, over Al, the undesired heterocyclic compound was over 15%. This indicates that the reaction between diamines and ketones has a significant potential to form heterocyclic compounds unless the interaction between these is kept to a minimum by the use of a continuous flow reactor as proposed by Speranza et al. (16) or by other methods. 

Biodesulfurization (BDS) is the excision (liberation or removal) of sulfur from organosul-fur compounds, including sulfur-bearing heterocycles, as a result of the selective cleavage of carbon-sulfur bonds in those compounds by the action of a biocatalyst. Biocatalysts capable of selective sulfur removal, without significant conversion of other components in the fuel are desirable. BDS can either be an oxidative or a reductive process, resulting in conversion of sulfur to sulfate in an oxidative process and conversion to hydrogen sulfide in a reductive process. However, the reductive processes have been rare and mostly remained elusive to development due to lack of reproducibility of the results. Moderate reaction conditions are employed, in both processes, such as ambient temperature (about 30°C) and pressure. 

The synthesis of the polycyclic 5-5-6-5 derivative 81 was realized by nucleophilic substitution of the 5,6-dichloro[ 1,2,5]oxadiazolo[5,4-7]pyrazine 79 with 5-aminotetrazole 80 (Scheme 17). This conversion took place at room temperature and the product 81 was isolated in moderate 36% yield. Many other heterocyclizations with N,N, N,0-, /V,.Y-bidentate nucleophiles gave the corresponding reaction in up to 93% yield <1997CHE1352>. 

The low selectivity affects the synthetic interest of homolytic arylation from two points of view. The first concerns the position of substitution generally all the free positions are substituted, giving very complex mixtures of isomers. Thus, for example, quinoline gives all the seven possible isomers in appreciable amounts.This is in contrast to all the homolytic substitutions described in the previous sections, which lead to exclusive attack at the 2- and 4-positions. The other aspect concerns the conversions of the heterocyclic compounds, which are always very low, usually lower than 1%. If the conversions are high, the mixture of the reaction products becomes much more complex. Thus with quinoline it can be easily foreseen from the partial rate factors (Table IX) that not only all the possible 21 diphenylquinoline isomers, but also... 

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