Amidines enamines

Formally analogous to the foregoing Grignard additions are the intramolecular condensations of amides with aromatic systems, found in the Bischler-Napieralski reaction 101), which is of particular interest in isoquinoline and indole alkaloid syntheses (102). Condensations of amidines with reactive methylene compounds also led to enamines (103-106). 

A similar strategy has been used to prepare pyrimidines, as well as pyra-zoles and isoxazoles by reacting the enamine intermediate with a variety of bidentate nucleophiles [78]. Microwave irradiation of a cyclic 1,3-diketone 49 and acetal 45 in water generated the corresponding enaminoketone 50 in situ which reacted with amidines, substituted hydrazines or hydroxylamine in only 2 min in a one-pot process to give 4-acylpyrimidines, pyrazoles or isoxazoles, respectively (Scheme 20). 

Azines have been prepared by initial condensation of diethoxyphosphinyIhydrazine anions with aldehydes or ketones (Scheme 9). Phosphoryl azides undergo 1,3-dipolar cycloaddition to 2-tetralone enamines to give triazolines, possibly en route to amidines. A full paper on the addition of diethyl dibromophosphoramidate to alkenes(leading to the synthesis of 2-bromoalkylamines) has appeared. ... 

The formimidoyl group can be transferred onto either amines, alcohols or CH-active compounds without use of a catalyst, providing amidines or aldimines and enamines, respectively [31... 

For the preparation of the anticipated heterocyclic library compounds (Scheme 6.257), solutions of the prepared enamine synthons were split and diluted with an appropriate solvent, and 1.2 equivalents of a dinucleophile (hydrazine, hydroxylamine, amidines see Scheme 6.257 for more complex building blocks) was added. Subsequent exposure to microwave conditions in acetic acid/DMF mixtures... 

N-Chlor-amidine konnen an Enamine unter Bildung von Imidazolen addiert werden136-138. Die Umsetzung verlauft iiber 4-Amino-4,5-dihydro-imidazole als Zwischenprodukte, die in einigen Fallen auch isoliert werden konnen137,139. 

N,N-Disubstituierte N -(4-Methyl-benzolsulfonyl)-amidine, die sich z.B. durch Cycloaddition von 4-Methyl-benzolsulfonyl-azid an Enamine und spontane Folgereaktionen herstellen lassen, konnen mittels Lithiumalanat direkt zu tert. Aminen reduziert werden1. 

Enamines contain electron-rich double bonds and thus react readily with azides (in many cases at room temperature). Only one addition product is formed, namely a 5-amino-A2-triazoline, a result of electronic control.22 -223 Thus l-(p-nitrophenyl)-4-ethyl-5-morpholino-A2-triazoline (44) arises from the addition of p-nitrophenyl azide to 1-morpholino-l-butene (43). The addition products rearrange by heating into amidines (45).224... 

Enamines react with aryl azides to give 5-arnino-A -triazo-lines which can be thermolyzed to amidines (see preceding... 

Sulfonyl azides react rapidly (at room temperature) with enamines, and here, too, no triazolines are isolated. The reaction products nevertheless can be easily explained when an intermediate triazoline is postulated. The hypothetic triazoline can then decompose in three different ways leading either to amidines and nitrogen, or to amidines and diazoketones, or to triazoles and sulfonamines.226-241-270-272 A typical example of each mode of decomposition is given in Scheme IX. 

An entire series of heterocyclizations is based on a-cyano-/3,/3-bis(acetyl)enamines (84JOC4696). When treated with weak bases, compounds 28 give amidine intermediates (29), which undergo cyclization yielding five-membered ring derivatives (30). The subsequent hydrolysis of 30 affords high yields of pyrrolinones (31). 

A reverse variant of this reaction is the interaction of enamines with amidines in the presence of an equimolar amount of bromine. Bromine at-... 

A series of special linkers and cleavage strategies has been developed for the release of amines from insoluble supports (Table 3.23). These include the attachment of amines as triazenes, enamines, aminals, amidines, sulfonamides, sulfinamides, hydrazines, or amides. 

Thioamides are suitable intermediates for the preparation of amidines, thiazoles, and thiophenes. Thioamides have mainly been prepared on insoluble supports by C-acylation of enamines or C,H-acidic compounds with isothiocyanates (Entries 1-3,... 

Although the addition of arylsulfonyl azides to enamines usually leads to amidines by loss of nitrogen from the intermediate triazoline adduct, when an electron-withdrawing substituent is present in the -position of the... 

An unusual course of thermolysis occurs in 5-amino- and 5-alkoxytri-azolines, which are formed only as intermediates in the reaction of enamines and enol ethers with azides bearing electron-withdrawing groups it involves cleavage of the N-l/N-2 as well as the C-4/C-5 bonds of the triazoline ring to yield diazoalkanes and imines with one fewer carbon than in the triazolines (amidines and imino ethers) (Scheme 144)233.250 272 431-433 in a cycloelimination reaction, the reverse of diazoalkane-imine cycloaddition. The intermediate formation of a diazonium zwitterion is suggested,233,247 but whether the thermolysis occurs in a one- or two-step reaction is not established. 

It turns out that we must protect the phenol as its methyl ether 127 and that 126 is best used as an amidine-ester rather than the double enamine. The synthesis is then quite short. We have barely scratched the surface of aromatic heterocyclic synthesis in this chapter but the encouraging message is that cyclisation is easy and that cyclisations to form aromatic compounds are the easiest of all. Disconnect with confidence ... 

Bifunctional nucleophilic reagents, such as ketones, enamines, / -diketones and their derivatives, amidines, thioureas, thioamides, dithiocar-bamates, and others, are very often employed in cyclizations with azine derivatives, resulting in the formation of annelated five-membered cycles (84UK1648 85KGS1011). The structure of all these 1,3-dinucleophiles feature a double bond conjugated with an anionic center or with a heteroatom bearing the lone pair of electrons (Scheme 5). 

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