Enamino nitriles

Polyquinolines have also been obtained by a post-polymerization thermal treatment of poly(enamino nitriles) (93). The resulting polymers show excellent thermal stabiUty, with initial weight losses occurring between 500 and 600°C in air (tga) under nitrogen, initial weight loss occurs at about 600°C and there is a 20% weight loss up to 800°C. 

Conventional conversion of amide, lactam, imide, and urea carbonyl groups into enaminones, enamino esters, or enamino nitriles requires prior activation of the carbonyl groups either by alkylation to imino ethers, followed by reaction with activated methylene groups, or by thiation, e.g. with P2S5, to thiocarbonyl groups followed by alkylation (and possibly also oxidation), and, again, subsequent reac-... 

In another approach (Scheme 92) enamino nitriles 249 serve as starting materials for pyrimidine syntheses. After transformation with triethyl orthoformate to 2-ethoxymethylenimino-3-carbonitriles (250), these are cyclized with semicarbazide to pyrano[2,3-d]pyrimidin-3-yl ureas (251). Dichlorotri-phenylphosphorane reacts in a second cyclization to give l,2,4-triazolo[l,5-... 

The well-known Thorpe-Ziegler condensation reaction (Ref. 2) involves the nucleophilic addition of a carbanion to an electrophilic center. Starting from adiponitrile, enamino nitrile 9 is recovered. Catalytic hydrogenation of this compound gives trans AMCPA as the major isomer (scheme 4) ... 

With enamino nitrile 9 intramolecular hydrogen bonding cannot take place so a rapid isomerization occurs between 13a and 13b giving rise to the trans AMCPA as the major isomer after hydrogenation. Isomerization to 13b is reinforced also by the slower rate of hydrogenation of a nitrile group than an aldimine one. 

Only few reports deal with a para photocycloaddition as the major reaction path. Recently, however, several cinnamide derivatives like 21 were efficiently transformed into the corresponding para adducts 22 (Sch. 6) [37]. Yields higher than 90% could be achieved. The para photocycloaddition is also observed with naphthalene derivatives like 1-acetylnaphthalene 23 and captodative enamino nitriles as 24 [38]. Other captodative substituted alkenes [39] as well as the fluorinated uracil derivative 26 [40] are transformed in the same way. Especially in the cases of 21 and 23, the... 

Polysubstituted dihydropyridines were also considered as targets. Condensation of LI with enamino ester 9.16 and enamino nitrile 9.17 under standard Hantsch conditions only proved successful for the latter, furnishing the pyridine library L6 (1280 members). Oxidation of the initially formed dihydropyridines is presumably favored due to the highly conjugated system formed (Fig. 9.12). Hantsch condensation with cyclic enamino esters 9.18 and 9.19a-f was also successful, providing respectively the bicyclic libraries L7 (1280 members) and L8 (7680 members. Fig. 9.12). 

The acylation of RLi or RMgBr by nitriles (cyanides) is an effective way to make ketones (Chapr and here we see the cyanide version of an intramolecular Claisen ester condensation. One cy-makes an enolate , which attacks the other. The resulting imine tautomerizes to the coni. . enamino nitrile. 

Names, P., Balazs, B., Toth, G., Scheiber, P. Synthesis effused heterocycles from 3-enamino nitrile and carbonyl compounds. Synlett... 

Photolysis of 4-amino-iV-methylthiazolium salts gives enamino nitriles by isomerization and hydration of the hitherto unknown quasi-aromatic 2-imino-2-dihydroazete intermediates. 

Yet another reaction used in the synthesis of 2,7-naphthyridine derivatives involves intramolecular cyclization of enamino nitriles under the action of acid catalysts. Thus compound 153 underwent cyclization to form 1-hydroxy-2,7-naphthyridine 154, used in the synthesis of sedative agent 155 (1988USP4859671). 

Analogous cyclization of enamino nitrile 156 in PPA afforded benzo[c][2,7]nap-hthyridine 157, which was converted into perlolinium chloride 158 (herbaceous alkaloid perloline 159) (1985CZ139). 

Because of the participation of the enamine double bond in the resonance of the aromatic ring of heteroaromatic /J-enamino esters, the group frequency character of the individual bands is low. Thus the El band is essentially vc=Q. Similarly, jS-enamino nitriles do not exhibit coupled vibrations since the nitrile absorption does not participate.24,61... 

The syntheses, properties, and chemistry of heteroaromatic /J-enamino nitriles have been reviewed extensively.166 Therefore, this section deals mainly with partially saturated heterocyclic /3-enamino nitriles in addition, some further reactions of heteroaromatic / -enamino nitriles are briefly described. 

In the IR spectra, the partially saturated heterocyclic /S-enamino nitriles do not exhibit the normal group frequencies that the corresponding esters display. The comparison of the 13C-NMR spectra of nitriles 299,300,302, and 305 with those of the esters 8,71, and 72 reveal for the nitriles a greater high-field shift of 27 ppm (Table III). As a consequence, it is concluded that in the enamino nitriles the double bond is more polarized than that of the corresponding esters several canonical forms can be discussed (Scheme 85). This difference in polarization (8, 71, and 72 versus 299, 300, 302, and 305) leads to several significant differences in the chemical behavior, which are briefly discussed in the following sections. 

The enamino nitriles 299, 300, and 302 react smoothly with various isocyanates to afford heterocondensed 4-amino-2-oxopyrimidines (306).172... 

In contrast to the broad applicability of heterocyclic / -enamino esters, the corresponding enamino nitriles with imido esters, phenylazide, or diamines, thermally as well as photochemically, give no reasonable products. 

Dihydro-4/7-l,3-oxazines (269) can be prepared in two steps first the addition of allenyl nitriles and 3-aminopropanol to give enamino nitriles (268), and then treatment of these products with a catalytic amount of sodium ethoxide at 200-250°C (Scheme 77) <81H(16)1889>. 

J-Enamino nitriles also serve as suitable substrates for aza-annulation reactions with various acrylate derivatives, and both acyclic and cyclic enamino nitriles have been used in this process for the construction of alkaloid skeletons. As illustrated in equation 80, substituted pyridone 390 was prepared in good yield through aza-annulation of enamino nitrile 389 with acryloyl chloride (64).57,59... 

Cyclic (S-enamino nitriles have been successfully employed in heterocycle synthesis through aza-annulation with both methyl acrylate and acrylonitrile. Monocyclic P-enamino nitrile 400 underwent aza-annulation with methyl acrylate in the presence of NaH to give 401, which was reduced with diborane to give 402 and 403 in a ratio of 5 1 (Scheme 34)." Quinolizidine 402 was carried on directly to ( )-epilamprolobine (404), or alternatively, epimerized with NaH to 403 and transformed into ( )-lamprolobine (405). 

In the first step of this synthesis, the pyrimidine derivative (123) was prepared from an enamino-nitrile and trichloroacetonitrile, then this compound was treated with phenylisothiocyanate to give (124) in 75% yield (Equation (38)) <82JCS(Pi)2667>. 

Another type of bicyclic 2-pyridones 31 results from the SnCL-promoted cyclocondensation of (3-enamino nitriles with malonates [88] ... 

A second route to 78 was first attempted from 79 0,91 Unlike 75 above, 79 did not cyclize in the Dieckmann reaction, so it was converted to the corresponding dinitrile 80 for Ziegler-Thorpe ring closure. This cyclization was successful, and exposure of the resulting enamino nitrile to acid hydrolysis and then Jones oxidation yielded ketolactone 81. In this case the carbene insertion failed. These differences in the fates of closely related carbenes presumably reflect changes in dynamic conformation as a function of specific structure. In contrast to the carbene insertion, the thermal reaction in the presence of palladium-on-carbon used previously on 77 did succeed with 81, giving directly a modest yield of 78. 

A related route reacted enamino-nitrile I.I7S with phosgene (another carboxyl surrogate) to give 7.27d. 5 Methanolysis of the acid chloride gave methyl 3-amino-... 

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