Ketene aminals

Irradiation of 3,5-disubstituted isoxazoles in alcoholic solvents gave reaction products such as acetals incorporating the reaction solvent. The use of triethylamine in acetonitrile media produced ketene-aminals by reductive ring cleavage. The reductive ring cleavage product was also obtained by irradiation of the isoxazole in alcohol in the presence of copper(II) salts (Scheme 3) (76JCS(P1)783). 

Analogously, the reactions of ketene aminals with ketene or dimethyl ketene gave y-amino-a-pyrones and the linear acylation products, respectively 422). 

The formation of four-membered-ring sulfones and a-sulfonyl amides has also been applied to the reaction of methanesulfonyl chloride with ketene aminals and acetals (470-473). 

In context with the formation of peraminosubstituted 1,4,5,8-tetraazaful-valenes of type 85 it must be mentioned that the bis-vinylogous compounds 94 can be easily prepared by reaction of acetamidine with bisimidoylchlo-rides derived from oxalic acid (96S1302). In the course of a complex reaction a cyclic ketene aminal was produced it immediately underwent an oxidative dimerization to yield deeply colored TAFs. Tlieir high chemical stability can be compared with that of indigoid dyes and manifests itself, for example, by the fact that they are soluble in hot concentrated sulfuric acid without decomposition. Tire same type of fulvalene is also available by cy-... 

The synthesis of this ring system was achieved by the reaction of the ketene aminal 79 with 3-morpholino-l-ethyl-l,2,4-triazinium tetrafluoro-borate 78 to give 80 (89IZV494). Cyclization of 78 with the bifunctional nucleophile 81 gave the pyrrolo[3,2-e][l,2,4]triazinones 82 (88TL1431). This reaction represents the first example of orthocyclization onto the 1,2,4-triazine ring by the addition of dienophiles at C-5,6 (Scheme 20). 

A new entry to the 2,3-dihydroimidazo[l,2-c]pyrunidine system 18 is the reaction of N-acylimidates with imidazoline ketene aminals under focussed microwave irradiation <96SC453>. 

The cycloaddition between a nitrilimine 319 and an aroyl substituted heterocyclic ketene aminal 318 has been found to be stepwise, involving an initial nucleophilic addition of 318 to 319 followed by intramolecular cyclocondensation of the intermediate 320 providing fully substituted pyrazole 321 (Eq. 36) [92]. When Ar was the 2,4-dinitrophenyl group, the intermediate 320 was isolable and required forcing conditions (xylene, reflux, 10 h) to undergo cyclization ... 

Compound 133 was synthesized by the one-pot intermolecular cyclization of ketene aminal 132 with alkyl isothiocyanate (Equation 15) <1995BML1541, 1997BML651, 2002BMC1275>. 

New heterocyclic ketene aminals have been obtained in yields ranging from 60 to 94% [89] starting from ethyl lff-perimidine-2-acetate or acetonitrile and isocyanates (Scheme 8.63). 

Focused irradiation of N-acylimidates mixed with imidazolidine ketene aminals provides a new means of access to 2,3-dihydroimidazo-[l,2-c]-pyrimidines [90] (Scheme 8.64). 

Several approaches to the 1,2,3-triazole core have been published in 2000. Iodobenzene diacetate-mediated oxidation of hydrazones 152 led to fused 1,2,3-triazoloheterocycles 153 <00SC417>. Treatment of oxazolone 154 with iso-pentyl nitrite in the presence of acetic acid gave 1,2,3-triazole 155, a precursor to 3-(W-l,2,3-triazolyl)-substituted a,P-unsaturated a amino acid derivatives <00SC2863>. Aroyl-substituted ketene aminals 156 reacted with aryl azides to provide polysubstituted 1,23-triazoles 157 <00HC387>. 2-Aryl-2T/,4/f-imidazo[43-d][l,2,3]triazoles 159 were prepared from the reaction of triethyl AM-ethyl-2-methyl-4-nitro-l//-imidazol-5-yl phosphoramidate (158) with aryl isocyanates <00TL9889>. 

The aroyl-substituted heterocyclic ketene aminals 482 react with 4-chlorophenyl azide to give polysubstituted 1,2,3-triazoles 483 and imidazo[ 1. Z-r 1.2,4]triazoles 39 (Equation 112) <2000HAC387>. Polysubstituted 1,2,4-triazoles are formed by the nucleophilic attack of the ct-carbon of the azide. Then, through the cyclocondensation and aromatization sequences, the fused heterocycles resulted by a 1,3-dipolar addition at first, and then through a Dimroth rearrangement and deamination of chloroaniline <1992JOC184>. 

An interesting pyrrolo[l,2-tf]pyrimidine was described as the product of the reaction of the heterocyclic ketene-aminals 236 that was synthesized by cyclocondensation of ketene dithioacetals 237 and 1,3-diamino propane. These compounds reacted with diethyl oxomalonate that behaves as an hetero-enophile, yielding the corresponding products 238 in acceptable to good yield (Scheme 31). A mechanism that involves an aza-ene reaction, via adduct 239 which isomerizes to ketene aminal 240 to produce the lactam ring of 238, has been proposed <1999J(P1)321>. 

Treatment of the cyclic ketene aminal 267 with diethyl azodicarboxylate results in formation of the reduced ring system 268 (Equation 52), probably via an initial aza-ene reaction, followed by fragmentation and ring closure <2002T7791>. 

Ketene Acetals, Ketene Mencaptals, and Ketene Aminals. 99... 

As with other ketene aminals, inclusion of the donor groups in 5- or 6-membered rings (43 to 45) lowers the C=C barriers (60). The data for 44 and 45 are difficult to reconcile with a high C=C barrier for 42. 

In the first DNMR studies of push-pull ethylenes, a strong effect of solvent polarity on the C=C barriers was noted. Thus Kende et al. (64) found AG = 18.0 kcal/mol for 46a in N,/V-dimethylformamide (dielectric constant e = 38) and 19.4 kcal/mol in Ph20 ( = 4). Similar observations have been made by many other workers, and they have been seen as a strong support for a zwitterionic transition state. Kessler et al. (140) observed reasonably linear correlations between AG for two ketene aminals and the solvent polarity parameter T (141) with variations in AG of ca. 2.5 kcal/mol over T values between 25 and 46. Similarly, Shvo et al. (78) found linear correlations between log km and the polarity parameter Z (141) for three compounds from Table 12. 

Saczewski and colleagues reported a similar pathway when the A-aryl-A-(4,5-dihydro-l//-imidazol-2-yl)hydroxylamine hydrochlorides 37 were refluxed in acetone in the presence of acetylenic derivatives 38 carrying electron-withdrawing substituents (equation 10). However, when 37 free bases were used, the adducts rearranged at room temperature, producing only the ketene aminals 39 in poor yields (equation 11). 

Nitrile imines also undergo nucleophilic attack by enamines [e.g., the ketene aminals (386) that react to give the pyrazoles 388 (221)]. The intermediate adduct... 

Eine zweifachc Cyclisicrung zum Bcnzimidazol- und zum Pyrimidin-Ring wird bei der Reaktion von Tri-ethoxy-methan mit dem Keten-aminal I beobachtet52 ... 

Triazines are generally more reactive in [2 + 4] cycloaddition in comparison with 1,2,3-tria-zines. The wide variety of dienophiles can be employed enamines, enaminones, vinyl silyl ethers, vinyl thioethers, cyclic ketene jV,O-acetals, /V-phenylmaleimide, 6-dimethylaminopentafulvene, 2-alkylidene-imidazolidines (cychc ketene aminals), cyclic vinyl ethers, arynes, benzocyclopropene, acetylenes, and alkenes like ethylene, (Z)-but-2-ene, cyclopentene, cyclooctene and bicyclo[2.2.1]hept-2-ene, hexa-1,5-diene, cycloocta-1,5-diene, diallyl ether, cyclododeca-l,5,9-triene,... 

The reaction of ketene aminals 240 and methyl propiolate for 2 days gave addition products 241 in near-quantitative yields (Scheme 18). During the heating of addition product 241 (R = H) in methanol for 16 hours, first cis-trans isomerization then ring closure occurred to give tetrahy-dropyrido[l,2-a]pyrimidin-6-one 242 (R = H) (86H2247). When the reac-... 

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