Protonation of γ‐Butyrolactone and γ‐Butyrolactam

Abstract Abstract: γ‐Butyrolactone and γ‐butyrolactam were reacted in the superacidic systems XF/MF5 (X=H, D; M=As, Sb). Salts of the monoprotonated species of γ‐butyrolactone were obtained in terms of [(CH2)3OCOH]+[AsF6]−, [(CH2)3OCOH]+[SbF6]− and [(CH2)3OCOD]+[AsF6]− and the analogous lactam salts in terms of [(CH2)3NHCOH]+[AsF6]−, [(CH2)3NHCOH]+[SbF6]− and [(CH2)3NDCOD]+[AsF6]−. The salts were characterized by low temperature Raman and infrared spectroscopy and for both protonated hexafluoridoarsenates, [(CH2)3OCOH]+[AsF6]− and [(CH2)3NHCOH]+[AsF6]−, single‐crystal X‐ray structure analyses were conducted. In addition to the experimental results, quantum chemical calculations were performed on the B3LYP/aug‐cc‐pVTZ level of theory. As in both crystal structures C⋅⋅⋅F contacts were observed, the nature of these contacts is discussed with Mapped Electrostatic Potential as a rate of strength.


Introduction
Many natural products include a γ-butyrolactone or γ-butyrolactam moiety as structural element. [1,2] Especially the γbutyrolactone motif is present in about 10 % of all natural products. [3][4][5] In total syntheses, a common strategy to synthesize the γ-butyrolactone motif is the Baeyer-Villinger oxidation. [2,6] Herein, an ester is formed from a ketone by using peroxyacids or peroxides. The Beckmann rearrangement instead, which is used to obtain γ-butyrolactam motifs, is the rearrangement of an oxime into an amide under ring expansion. [2,7] Another synthesis strategy for both cyclic compounds is the catalyzed cyclodehydration of the corresponding hydroxyl acid, [8] respectively amino acid. [9] Interestingly, in case of γ-butyrolactone, both, the lactonization [8] and the hydrolysis, [10] are acid-catalyzed (see Equation 1).
Since both cyclic compounds are abundant in natural products and their protonated species can occur in syntheses or metabolic cycles, they are of great interest. However, so far, only NMR-spectroscopic investigations of protonated γ-butyrolactone and protonated γ-butyrolactam are reported. [11,12] Under acidic conditions, a ring opening reaction can occur, which prompted us to investigate the reaction behavior of both compounds in superacidic media.

Protonated γ-Butyrolactone
In Figure 1, the Raman and infrared spectra of [(CH 2 ) 3 Table S1, all observed and calculated frequencies are listed (see Supporting Information). In consequence of the C 1 symmetry of the starting material, [13] no higher symmetry, such as the ideal C s , is expected for the protonated species. We assumed C 1 symmetry with 33 fundamental vibrations, active in Raman and infrared spectra, for the cation.
A first evidence for a successful protonation is given by the ν(OH) vibration in the infrared spectra of (1) and (2), which occurs at 3528 cm À 1 (1) and 3460 cm À 1 (2), respectively. In the corresponding Raman spectra, no lines are observed, because of the poor polarizability of the OH stretching vibration. Contrariwise, the OD stretching vibration of [(CH 2 ) 3 OCOD] + [AsF 6 ] À (3) is detected at 2239 cm À 1 (Ra) and 2307 cm À 1 (IR). The redshift is in good agreement with the Teller-Redlich rule for an H/D isotopic effect. [14] Considering the constitution of the synthesized cation, the ring breathing vibration at about 880 cm À 1 (Ra, IR) indicates the preservation of the ring structure. Changes in vibrational spectra are observed for the CO stretching vibrations. Due to the protonation, the former CO double bond is weakened and the ν(CO) occurs at 1523 cm À 1 (Ra) (1), at 1522 cm À 1 (IR) and 1526 cm À 1 (Ra) (2) and at 1510 cm À 1 (IR and Ra) (3).
Compared to the neutral compound, [15] this redshift amounts up to 260 cm À 1 . In contrast, the former CO single bond, belonging to the lactone moiety, is strengthened and the  corresponding stretching vibration is detected at 1684 cm À 1 (IR) and 1613 cm À 1 (Ra) (1), at 1616 cm À 1 (IR) and 1637 cm À 1 (Ra) (2) and at 1607 cm À 1 (IR) and 1619 cm À 1 (Ra) (3). The blue shift is up to 306 cm À 1 compared to γ-butyrolactone. [15] The other CO stretching vibration of the ring skeleton is detected at about 960 cm À 1 (IR, Ra) for the protonated species (1 and 2) and at about 1000 cm À 1 for the deuterated one (3). The δ(COH), respectively the δ(COD), is observed in the range between 1084 cm À 1 and 1089 cm À 1 for (1) and (2) and at 912 cm À 1 (IR) and 916 cm À 1 (Ra) for (3). More vibrations, which are assigned to the AsF 6 À , respectively the SbF 6 À anion, are observed than were expected for an ideal O h symmetry. Here, in the Raman spectra more than three lines and in IR spectra more than two bands are detected. The increased number of vibrations indicates a lowered symmetry of the structure of the anions.
For protonated γ-butyrolactam, C 1 symmetry with 36 IR and Raman active vibrations, is expected. The assumption of retaining the ring structure is confirmed by the ring breathing vibration at about 900 cm À 1 (Ra, IR).

Theoretical Calculations
All quantum chemical calculations were carried out on the B3LYP/aug-cc-pVTZ level of theory. In both crystal structures C···F contacts are observed. Usually, organic cations of hexafluoridometalates only possess hydrogen bonds as interionic interactions. In the case of protonated γ-butyrolactone and γbutyrolactam, we found C···F contacts. Such contacts, which differ from hydrogen bonds, have only rarely been observed. [24][25][26] To investigate the nature of these contacts, Mapped Electrostatic Potentials (MEP) of the free cations [(CH 2 ) 3 OCOH] + and [(CH 2 ) 3 NHCOH] + were calculated. The cation-anion contacts together with the respective MEPs are illustrated in Figures 7 and 8. MEP calculations together with Natural Population Analysis charges (NPA) for the neutral compounds as well as for the protonated species of γbutyrolactone ( Figure S1) and γ-butyrolactam ( Figure S2) are displayed in the Supporting Information.
hole [27] indicates that the positive charge is located at this atom. This assumption is confirmed by comparing the NPA charges of the neutral compound and the protonated species. For both γbutyrolactone and γ-butyrolactam, the same trend is observed. Due to the protonation, changes of the NPA charges are detected only for the OCO group, respectively the OCN group. For all other atoms NPA charges remain nearly unaffected. Compared to the respective neutral compound, the positive charge of the carbon atom is increased, while the negative charges of the O (or N) atoms are decreased. For electron deficient sp 2 -hybridized carbon atoms, especially carbonyl groups, investigations on their ability to develop interatomic contacts were performed. [28,29] The associated MEP value at the π-hole of [(CH 2 ) 3 OCOH] + (127.4 kcal/mol) is calculated to be more positive compared to the value of [(CH 2 ) 3 NHCOH] + (118.2 kcal/mol). The analysis predicts a stronger C···F contact in protonated γ-butyrolactone than in protonated γ-butyrolactam. This prediction is confirmed by the crystal structure of (1), exhibiting the formation of two C···F contacts (C1À F3: 2.875(3) Å and C1À F4ii: 2.957(3) Å), which are below the sum of the van der Waals radii. [18] In contrast, only one C···F contact (C1À F4Aii: 2.787(7) Å) is found in (4). The more positive MEP value of [(CH 2 ) 3 OCOH] + represents the ability to form two contacts, which are therefore slightly weaker than that in (4). Summarizing these results, it can be stated that in protonated γbutyrolactone, the localization of the positive charge on the sp 2 -hybridized carbon atom is even stronger than in protonated γ-butyrolactam.

Conclusions
In this work, the reaction behaviors of γ-butyrolactone and γbutyrolactam in the superacidic systems XF/MF 5 (X = H, D; &bk,M = As, Sb) were investigated. Only salts of the respective monoprotonated species were obtained and no ring opening reaction was observed. The salts were characterized by Raman and IR spectroscopy. In case of [(CH 2 ) 3 OCOH] + [AsF 6 ] À (1) and [(CH 2 ) 3 NHCOH] + [AsF 6 ] À (4), single-crystal X-ray analyses were performed. In both crystal structures C···F contacts between anion and cation, formed from the sp 2 -hybridized carbon atoms, were observed. In order to investigate the nature of these contacts, Mapped Electrostatic Potentials (MEP) of the cations were calculated. For both cations, regions of positive potential (π-holes) are located on the sp 2 -hybridized carbon atoms. The more positive π-hole MEP value was found for [(CH 2 ) 3 OCOH] + compared to [(CH 2 ) 3 NHCOH] + . Interestingly, this did not lead to the formation of a stronger C···F contact in (1), but to the formation of two weaker ones. In contrast, a stronger C···F contact is observed in (4), where the less positive MEP value is calculated for [(CH 2 ) 3 NHCOH] + .

Experimental Section
General Caution! The hydrolysis of AsF 5 , SbF 5 and the prepared salts (1-6) might form HF which burns skin and causes irreparable damage. Safety precautions must be taken while using and handling these materials.

Apparatus and Materials
The reactions were conducted in standard Schlenk technique using a stainless steel vacuum line. FEP/PFA reactors, closed with a stainless steel valve, were used to perform all reactions in superacidic media. The vacuum line, as well as the reactors, were dried with fluorine prior to use. Low temperature Raman spectroscopic  . Interatomic contacts are drawn as dashed lines. In the background of the cation, the MEP is illustrated with a color range of 81.6 kcal/ mol (red) and 125.5 kcal/mol (blue), isoval. = 0.0004. Symmetry codes: i = x, À 1 + y, z; ii = À 1 = 2 + x, 1 = 2 À y, À z; iii = À x, À 1 = 2 + y, 1 = 2 À z.