Theoretical Study of Ammonolysis of Monobactams: Kinetic Role of theN-Sulfonate Group

Díaz, Natalia; Suárez, Dimas; Sordo, T. L.

doi:10.1002/1522-2675(200201)85:1<206::aid-hlca206>3.0.co;2-l

Cited by 5 publications

(1 citation statement)

References 37 publications

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“…This plus the experimental accessibility has resulted in extensive investigations of the rotational isomerism and barriers in the amide bond . 2‐azetidinones are of particular interest due to their inclusion in the β‐lactam antibiotics penicillins and cephalosporins, and many investigations have been devoted to the development of these β‐lactam antibiotics . They are also important precursors in numerous reactions as they are easily converted into unsaturated ketones and 2‐piperidones .…”

Section: Introductionmentioning

confidence: 99%

A theoretical and NMR lanthanide‐induced shift (LIS) investigation of the conformations of lactams.

Abraham

Filippi

Petrillo

et al. 2017

Magnetic Reson in Chemistry

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Molecular mechanics (MM) with MMFF94 and MMX force fields and ab initio (RHF/6-31G*,RHF/6-311G**, and B3LYP/6-311G**) calculations are used with lanthanide-induced shift (LIS) to investigate the conformations of N-methyl-2-pyrrolidone 1, N-methyl-2-piperidone 2, ε-caprolactam 3, γ-valerolactam (1,5-dimethyl-2-pyrrolidone) 4, 2-azetidinone 5, 4-methyl azetidinone 6, 4-phenyl azetidinone 7, and N-methyl-4-phenyl azetidinone 8. The Yb(fod) paramagnetic induced shifts of all the H and C nuclei are measured and the corresponding diamagnetic complexation shifts obtained by the addition of Lu(fod) . The complexation model (two-, three-, or four-site) used depends on the relative rates of the processes involved. The amide inversion is the same order as that of the 5- and 6-membered lactam rings and much faster than the lanthanide complexation and the inversion of the 7-membered ring. Both MM and ab initio calculations give an envelope conformation for 1 with C-4 out of the ring plane in agreement with the LIS analysis. For the piperidone ring of 2, the half-chair is calculated as the most stable form. The LIS analysis confirms this but cannot exclude a small amount (<2%) of the boat conformation. For 3, the LIS analysis gives a minimum for 90:10% chair to boat conformation, and 4 exists in two envelope conformations with the C -Me ps-eq and ps-ax in an eq/ax ratio of 94:6%. In 2-azetidinone 5, the ab initio calculations gave both ring and nitrogen planar, but the MMFF94 calculations give a butterfly ring and pyramidal nitrogen. The LIS analysis for 5 gave good agreement (Rcryst 0.46%) for the MMFF94 geometry with endo NH but the planar ab initio geometries worse agreement (Rcryst = 1.1%). For 4-methyl-2-azetidinone 6, the MMFF94 geometry gave good agreement (Rcryst 0.96%) with two butterfly conformations with axial and equatorial methyl groups in 1:1 ratio. All the planar geometries gave worse agreement (Rcryst >1.5%). In 4-phenyl azetidinone 7, the MMFF94 geometry with 60% of the axial conformer gave Rcryst 1.2% but the other geometries Rcryst >1.5%. In contrast the N-methyl-4-phenyl-2-azetidinone 8 gave good agreement for all the geometries. The butterfly conformation gave Rcryst 1.1% for 80% of the axial conformer and the planar geometries Rcryst 0.98%. The LIS results confirm the ab initio and MM optimised geometries, but the conformer energies at times differ from the calculated values. They also differ considerably from the corresponding values for the lactones studied previously, and possible reasons for this are discussed.

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Section: Introductionmentioning

confidence: 99%

A theoretical and NMR lanthanide‐induced shift (LIS) investigation of the conformations of lactams.

Abraham

Filippi

Petrillo

et al. 2017

Magnetic Reson in Chemistry

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A Combined Theoretical and Experimental Research Project into the Aminolysis of β‐Lactam Antibiotics: The Importance of Bifunctional Catalysis

Díaz¹,

Suárez²,

Sordo³

et al. 2003

Eur J Org Chem

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This paper reports the results of experimental work on the aminolysis of penicillin (6-APA) and monobactam (aztreonam) antibiotics by propylamine or ethanolamine. In general, aztreonam is slightly more reactive than 6-APA, despite the common assumption that the amide bond should be less activated in monobactams. Intriguingly, when ethanolamine acts as the nucleophile, the corresponding rate law has a kinetic term proportional to [RNH 2 To complement the experimental observations, the rate-determining free energy barriers in aqueous solution for various mechanistic pathways were computed by standard quantum chemical methodologies. From previous theoretical work it was assumed that the aminolysis of β-lactams proceeds

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Specificities of application of the supermolecule method to the calculation of reaction mechanisms in a protonodonor medium. Ethylene carbonate aminolysis in methanol

Zabalov

Тигер

2017

Theor Chem Acc

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Theoretical Study of Ammonolysis of Monobactams: Kinetic Role of theN-Sulfonate Group

Cited by 5 publications

References 37 publications

A theoretical and NMR lanthanide‐induced shift (LIS) investigation of the conformations of lactams.

A theoretical and NMR lanthanide‐induced shift (LIS) investigation of the conformations of lactams.

A Combined Theoretical and Experimental Research Project into the Aminolysis of β‐Lactam Antibiotics: The Importance of Bifunctional Catalysis

Specificities of application of the supermolecule method to the calculation of reaction mechanisms in a protonodonor medium. Ethylene carbonate aminolysis in methanol

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