Missing Link in the Homologous Series of Lactams: The X-ray Structure of Valerolactam

Abstract

Lactams are an important class of heterocyclic compounds and are widely used for industrial and pharmaceutical purposes. Even decades after initial lactam syntheses, research on their physical and chemical properties is still rewarding. It delivers valuable information on the reactivity of lactams and their conformational behavior. For the small- and medium-sized parent lactams, the X-ray structures have been well-known, except for the “missing link”, the six-membered valerolactam. An X-ray structure of valerolactam is described here for the first time, stimulating a comparative discussion of the homologous lactam series. The experimental solid state conformation of valerolactam differs significantly from the calculated and energy-minimized ones reported in the literature. The amide bond length in valerolactam is more or less equal to that in other lactams. A comparison with the structure of cyclohexene revealed striking similarities arising from the partial C–N double bond in valerolactam caused by amide resonance.

Does the Exception Prove the Rule? A Comparative Study of Supramolecular Synthons in a Series of Lactam Esters

“…The ester moiety is in a clear equatorial position (Figure 6a). As observed for the parent valerolacta m (CSD code: HIQJOJ) 11 (Fig. 6c).…”

“…The ester moiety is in a clear equatorial position (Figure a). As observed for the parent valerolactam (CSD code: HIQJOJ) two molecules of 5 form an R 2 2 (8) amide dimer via N–H···O hydrogen bonds (Figure b). The dimerized lactams are connected via C–H···O interactions between C4 and the carbonyl oxygen forming bands in the direction of the b axis.…”

“…(Details on the X-ray structure of the resulting diacid are given in the Supporting Information.) However, structural and hydrolytic studies for the unsubstituted parent lactams have shown that it is not differences in the amide bond length that are responsible for their varying hydrolytic behavior. , In fact, the formation of the tetrahedral intermediateconnected to the overall conformation of the lactam and potential substituentswas shown to be rate-determining, not so much the fission of the C–N bond. So it cannot be ruled out that also the axial or equatorial position of the N α substituent has an influence on the rate of lactam hydrolysis.…”

“…Ethyl 1-methyl-2cyclohexanonecarboxylate (9) was synthesized from ethyl 2-cyclohexanone-carboxyla te, methyl iodide and potassium carbonate according to a literature procedure. 45 Methyl 47 (10) and ethyl 7-cycloheptanonecarboxylate 48 (11) were synthesized from cycloheptanone using the respective dialkylcarbonate and sodium hydride. The synthesis of caprolactam ester 12 has been described earlier.…”

“…As observed for open amides, lactams also possess partial C–N double bond character, which goes in hand with resonance stabilization. While the amide bond lengths for small- and medium-sized lactams (ring sizes 4–9) are rather consistent, their hydrolytic stability is not with the four and six membered rings being hydrolyzed significantly faster …”