Ketenimines amides

Ketenimines are usually prepared from carboxyHc acid derivatives such as amides and imino chlorides via elimination and from nitriles via alkylation with alkyl haHdes under strong basic conditions (21,64). 

DCC, and l-methyl-2-chloropyridinium iodide (Mulcaiyama s reagent). Analogously, amides can be dehydrated with P2O5, pyridine, and AI2O3 to give ketenimines ... 

Both carbodiimides and ketenimines are reported to add to N-sulfinylsulf amides to give 3-imino- and 3-alkylidene-l,2,4-thiadiazetidine 1-oxides, (Scheme 135) (73BCJ2156, 75BCJ3259). The adducts were identified from both IR and NMR spectra and from hydrolysis products. 

The spiro-triazoline (380) can be converted into both the ketenimine (381) and the cyclobutanimine (382) (74JOC63). Triazolines formed by cycloaddition of azides to norbor-nene lead to munerous interesting norbornane derivatives (of. 78bsf(2)48s). 5-Hydroxytriazo-lines (383) afford the ring-contracted amide (384) by thermal dehydration (67mi411oo). 

In each case an intermediate, 5, can be isolated In contrast to the aminosilane reaction (see also Ref. 24), a Ge or Sn amide does not form the 0-M derivative, analogous to 5 . Addition of Et2AlNMe2 to a ketenimine leads to compound 6 (Ar = Ph or p-MeCgH4) , by a double insertion process ... 

The presence of two hydrogen atoms at the nitrogen in the amines permits subsequent prototropic isomerization with the formation of ketenimines. By way of contrast, reactions with primary phosphines lead to halogen-substitution products with retention of the bond and P-H bonds. The reaction of ketenimines with water in the presence of a catalytic amount of HCl proceeds smoothly and leads to a high yield of the corresponding amide. 

Ketenimines from carboxylic acid amides CHCONH C C N ... 

At-Tosylhydrazones, R R C=NNHTs, undergo a palladium-catalysed amidation with isocyanides (CN-R ) via a ketenimine intermediate in the presence of water. This allows access to amides, R R HC-CONHR , from carbonyl compounds via a one-carbon extension. ... 

NaH has been recommended for the benzylation of carbohydrates Direct esterification of phenols occurs quite readily if the resulting water is removed by means of a Dean-Stark trap A simple preparation of ketenimines from amides and a convenient synthesis of azoxy compounds, including aromatic-aliphatic ones have been published. 

Isoxazolium salts Trialkyloxonium salt Amidinium salts Ketenimines Diazomethane K-methyldiazotate Hexamethylenetetramine Azo compounds T riazenes p-Nitrobenzene-diazonium sulfate Sulfanilic acid, diazotized HCONH2, CHsC0NH2 Dimethylacylamines HC0N(CHs)2, CHsC0N(CHs)2 1-Benzyl-1,4-dihydro-nicotinamide N,N -Diethylnicotin-amide C0(NH )2, (CHs)2NCON(CHs)2 Phenyl isocyanate Carbodiimides Dicyclohexylcarbodi-imide, Di-p-tolyl-Antipyrine Imidazole 1-Acylimidazole N,N -Carbonyldi( azoles ) N, N -Carbonyldi-imidazole... 

The reactivity of ketenimines such as 146 is related to substituent R. Ketenimines were isolable when R was phenyl or alkyl. In contrast, ketenimines wherein R was halogen, thienyl, phenylthio, methylthio, or methylsulfonyl were sufficiently reactive to afford iminoethers (147) at -78°C in the presence of excess lithium methoxide. The trimethyl-chlorosilane-quinoline procedure satisfactorily converted all these substituted iminoethers to amides in good yields. The overall sequence proved amenable for use with cephalosporin acids, by prior protection of the carboxyl group as a silyl ester. Extension of this method to the penicillin series permitted the preparation of 6a-methoxyketenimine 149 and 6a-methoxyimino ether 150 from the corresponding methyl 6p-(2-chlorophenyl)acetamido and fi -dichloroacetamidopenicillanates, respectively. No further transformations of these substances were reported. 

A modification of the original Sankyo approach involves bromination of ketenimine (157 at -20 to -30°C (Saito et al., 1976). The putative intermediate (159) gives a 7a-methoxyketenimine 160 (55%) after reaction with methanolic lithium methoxide at -78°C. Analogously 164 was obtained from 162 via 7a-methoxyketenimine 163. The ketenimines could be prepared from their corresponding amides by reaction with PCI5 followed by silica gel chromatography and were readily identifiable by their characteristic IR absorption at 2000 cm . ... 

Keteniminium salts undergo [2-1-2] cycloaddition reactions with unreactive olefins, such as ethylene, cyclopentene, cyclohexene and styrol to give cyclobutane ammonium salts 23, which are readily hydrolyzed to give cyclobutanones 24. Likewise, reaction with acetylene derivatives affords cyclobutenylidene ammonium salts 25, which are also readily hydrolyzed to give the cyclobutenones 26. Some of the [2-1-2] cycloadducts obtained from keteniminium salts and olefines are shown in Table 4.17. The keteniminium salts are easily synthesized from suitable dimethylamides and phosgene, or trifluoromethanesulfonic acid anhydride. The reaction of the amide with phosgene generates a chloro compound 21, which is in equilibrium with the ketenimine salt 22. 

The amide 35 in which the aromatic ring is deactivated by a bromine atom has been found to undergo dehydration and cyclization, thus affording a mixture of the ketenimine 37 and small amounts of the 3,4-dihy-droisoquinoline 36 (71JCS(C)1796) (Scheme 18) (81HC139). 

Hydrogen chloride dimethyl sulfoxide Oxidative solvolysis in dimethyl sulfoxide a-Hydroxycarboxylic acid amides from ketenimines... 

Scheme 6 Reaction pathways of copper(I)-catalyzed multicomponent polymerization of diynes 9, sulfonyl azides 10, and diamines 11 or diols 12 A triazole intermediate, B ketenimine species, C N-sulfonyl amide...

A three-component reaction for the synthesis of functionalized benzimidazoles from terminal alkynes, o-aminoanilines, and / -tolylsulfonyl azide is developed by Wang and coworkers (Scheme 8.52). The C(sp)-H bond of alkyne was activated in this reaction via Cul-catalyzed azide-alkyne cycloaddtion (CuAAC) reaction which could lead to the formation of a ketenimine intermediate by the release of N2- The benzimidazoles could be obtained by intramolecular nucleophilic addition and subsequent elimination of amide intermediate with 2% H2SO4 under reflux conditions [91]. They also developed another protocol for the synthesis of substituted benzimidazole derivatives via a sequential three-component cascade reaction from sulfonyl azides, alkynes, and 2-bromoanilines using Cul as catalyst. Similarly, the C-H bond of alkyne was activated at the process of copper-catalyzed azide-alkyne cycloaddtion (CuAAC) reaction [92]. 

Lu, Wang et al. developed an efficient preparation of dihydropyrimidin-4-ones from readily available AT-(prop-2-yn-l-yl)amides and sulfonyl azides using Cul as catalyst (Scheme 8.108). This cascade reaction includes copper-catalyzed alkyne-azide cycloaddition, formation and intramolecular nucleophilic addition of ketenimine, and subsequent rearrangement. The C(sp)-H bond was activated through copper-catalyzed alkyne-azide cycloaddition process in this reaction [182]. 

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