Glutarimide formation

That the methyl group in the less substituted isomer of the enamine (20) is axial was borne out by the work of Johnson et al. (18) in the total synthesis of the glutarimide antibiotic //-dehydrocycloheximide (24). The acylation of the morpholine enamine of 2,4-dimethylcyclohexanone (25) with 3-glutarimidylacetylchloride (26), followed by the hydrolysis of the intermediate product (27) with an acid buffer, led to the desired product in 35 % yield. The formation of the product in a rather low yield could most probably be ascribed to the relatively low enamine-type aetivity exhibited by the tetrasubstituted isomer, which fails to undergo the acylation reaction, and also because in trisubstituted isomer one of the CHj groups is axial. Since the methyl groups in the product are trans to each other, the allylic methyl group in the less substituted isomer of the enamine should then be in the axial orientation. 

Acrylamide polymers in aqueous solution undergo thermal hydrolysis and cyclic imide formation. Acrylate, acrylamide and cyclic imide functional groups were detected when a poly(acrylamide) is heated at 150°C in water. The formation of intramolecular imide has been reported in literature. Moradi-Araghi, Hsieh and Westerman reported the formation of cyclic imide in acid, neutral and slightly basic media at 90° C.7 In acidic media, imide formation is favored. In neutral and basic media, both hydrolysis to acrylate and imide formation do occur, but hydrolysis is the dominant reaction. We speculate the high conversion of amine to amide is the result of transamidation, amidation and the nucleophilic addition of the amine to the glutarimide intermediate (Reaction 1). 

Irradiation of a tert-butyl alcohol solution of 6-ethoxy-4,5-dihydro-2(3H> pyridone (14) under conditions similar to those described for 12 gives two products, tert-butyl N-(ethoxyethylidene)carbamate (27) in 15% yield and glutarimide in 23% yield18. There is no indication of formation of the cyclobutyl analogue of 13. In aprotic solvent, ethoxyvinyl isocyanate (28) and glutarimide (29) are the major photoproducts formed. The gaseous byproducts from the irradiation of 6-propoxy-... 

The quantum yields of formation of tert-butyl N-(ethoxycyclopropyl)carbamate (13) from irradiation of 12 and of tert-butyl N-(ethoxyethylidene)carbamate (27) and glutarimide (29) from irradiation of 14 are moderately high and are shown in Table 2. The effect of the triplet quencher c/s-piperylene on the quantum yields has been examined. Over the concentration range 0.01—0.1 OM c/s-piperylene, no ap-... 

Comparing the structure of the monomer with that of the polymer as shown in Table I, we see that the polymerization of the / -carboxy-methyl caprolactam must involve isomerization of the monomer ring system. This isomerization may be described by several possible processes, all of which are characterized by reaction between the amide and acid group of the / -carboxymethyl caprolactam. Based upon the results of our studies on the structure of this polymer (5) we may eliminate confidently those processes according to which the formation of the glutarimide moiety results either by intrachain cyclization or by trans-cyclization of certain intermediate polymer structures. The former would involve a polymer formed by a conventional ring opening polymerization ... 

Expanding the range of application of chiral lithium amides led to desymmetrization of various glutarimides. Thus the use of 67 enabled the formation of 96 in up to 97% ee and as single diastereoisomer with a trans arrangement of the newly installed substituents (Scheme 67)107. 

Cyclization of aspartic acid and asparagine to form aspartimides, and to a lesser extent of glutamic acid and glutamine to form glutarimide is an acid- and base-catalyzed common side reaction in peptide synthesis (see also Section 2.2.2). In SPPS it is particularly troublesome when Asp-Gly, Asp-Ala, and Asp-Ser sequences are present,but also with Asp-Asn.P P Piperidine-catalyzed aspartimide formation can be very rapid,and in this context DBU is even worse than piperidine.P The formation of aspartimide is reduced by the addition of HOBt or 2,4-dinitrophenol, but more efficiently it is reduced by protecting the aspartyl amide bond with the 2-hydroxy-4-methoxybenzyl (Hmb) group (see Section 2.3.2).P 1... 

A construction of functionalised glutarimides relies on the doubly nucleophilic dianion that can be generated by C- and N-deprotonation, from a 2-tosyl-acetamide. Regioselective reduction to a piperidone can be achieved via formation of the stabilized enolate. 

In contrast to the AGT/j8-CyD complex, the NOE effect decreased for the H-5 protons and remained almost unchanged for H-3 protons when irradiating the protons in the meta position instead of the protons in the ortho position of the aromatic ring of AGT in the (+)-AGT/y-CyD complex (Fig. 6.6b). These data support a complex formation from the narrower primary side of y-CyD with the amino group ahead (Fig. 6.7b). The glutarimide ring is apparently less involved in the complex formation in this case. However, the involvement of the methyl group in complex formation by a still unknown mechanism cannot be completely excluded. Thus, as shown with this example, combined application of CE and a ROESY experiment may indicate the principal differences in the structure of analyte-CyD complexes in solution. 

The HR of A -protected glutamic acid esters 206 proceeds smoothly under electrochemical conditions to afford carbamates 207. The use of the cosolvent trifluoroethanol prevents formation of the cyclized glutarimide, which is a major byproduct (or only product) with conventional (basic) conditions using bromine and sodium methoxide or by running the electrochemistry in methanol. The several trifluoroethyl carbamates (e.g., 203) that were prepared in these electrochemical HR studies react with primary and secondary amines in the presence of sodium hydride to form unsymmetrical ureas. ... 

The use of [IrH5(PPr 3)2] 987 as catalyst for the selective C-C bond cleavage of mono- and dinitriles has been reported. This compound behaves as an ambiphilic catalyst for bringing about the one-pot three-component assemblage of alkenes, nitriles, and water resulting in the formation of glutarimides. ... 

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