2-Thiophenecarboxaldehyde: Adsorption & Synthetic/Analytical Applications

2-Thiophenecarboxaldehyde is a colourless to pale yellow liquid possessing a pungent odour at ambient temperatures. It reacts readily with multifunctional groups such as hydroxyl, amino, and thiol groups. 2-Thiophenecarboxaldehyde finds extensive application in organic synthesis, serving as an intermediate in numerous significant synthetic reactions. It may also function as a precursor material for optical applications and is employed in fields such as optoelectronic devices and organic light-emitting diodes (OLEDs).

The Adsorption Structure of 2-Thiophenecarboxaldehyde

Recently, many research groups have been studying structures of biomolecules adsorbed onto semiconductor surfaces in connection with the development of bio-related applications. The Ge(100)-2 × 1 reconstructed surface provides an excellent model of a semiconductor surface because the Ge(100)-2 × 1 reconstructed surface displays zwitterionic character. The zwitterionic dimers of the Ge(100)-2 × 1 reconstructed surface act as Lewis bases and acids, which facilitate the adsorption of molecules with multifunctional groups. Recent studies have shown that thiol groups react with Ge(100)-2 × 1 reconstructed surface under photo-excitation with 510 nm light. This reaction is useful as a photo-induced thiol detector. In terms of developing the other thiol detection applications, we have examined sulfur-containing compounds to understand how these molecules behave on the Ge(100)-2 × 1 reconstructed surface at room temperature. 2-Thiophenecarboxaldehyde (TPCA) is a good test molecule as a detector because its molecular structure is relatively simple and sensitive. Contrary to what is known about the Diels-Alder reaction which occurs in aqueous state, TPCA is expected to form several cycloaddition structures under UHV conditions through reactions involving the 2-Thiophenecarboxaldehyde diene and the dimer of the Ge(100)-2 × 1 reconstructed surface atoms. Beyond exposure of 0.25 mL, the stable [4 + 2] cycloaddition adducts were observed. Here, we sought to compare the adsorption structures of thiophene and 2-Thiophenecarboxaldehyde on the Ge(100)-2 × 1 reconstructed surface using high-resolution photoemission spectroscopy (HRPES) and density functional theory (DFT) calculations.[1]

We investigated the adsorption geometries and the exposure-dependent bonding states of TPCA molecules adsorbed onto the Ge(100)-2 × 1 reconstructed surface using HRPES and DFT calculations. The HRPES data suggested that the 2-Thiophenecarboxaldehyde molecules adsorbed onto the Ge(100)-2 × 1 reconstructed surface in three possible adsorption structures. The S-dative bonded structure was prevalent at low (15 L TPCA) exposure levels. The [4 + 2] cycloadduct structure, which includes stronger bonds, was prevalent around 100 L 2-Thiophenecarboxaldehyde. The [2 + 2]-C=O cycloadduct structure was prevalent at 900 L TPCA, and this structure was not observed in previous studies of thiophene adsorbed onto the Ge(100)-2 × 1 reconstructed surface. Oxygen atoms are strongly electronegative and can form a [2 + 2]-C=O cycloadduct structure more easily than the carbon atoms of thiophene can form a [2 + 2]-C=C cycloadduct structure on the Ge(100)-2 × 1 reconstructed surface. The electronegativity of oxygen could explain why oxygen atoms adsorb at the down dimer on the Ge(100) surface, which has a relatively positive charge. Ge(100)-2 × 1 reconstructed surfaces display zwitterionic properties that allow oxygen atoms to adsorb onto Ge(100) down dimers. The energies of the proposed adsorption structures were predicted using DFT calculations.

Cefixime using 2-thiophenecarboxaldehyde as derivatizing reagent

Cefixime [(6R,7R,E)-7-(2-(2-aminothiazol-4-yl)-2-(carboxymethoxyimino)acetamido)-8-oxo-3-vinyl-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid], is considered as an important and active member of third generation cephalosporin. The cefixime exists in off white crystals, melts over 250–220 °C and soluble in alcohol. 2-Thiophenecarboxaldehyde (2-TCA) 2 (also known as thiophene 2 carbaldehyde) is an aldehyde compound which is used for condensation process and an intermediate to manufacture pharmaceuticals, aroma compounds and pesticides. Alexandru et al. have utilized the 2TCA for condensation of alkylazulenes, however there is no any report for 2-TCA to be used as derivatizing agent for drug specially cefixime. 2-Thiophenecarboxaldehyde is a yellow colored liquid having 198 °C boiling point soluble in alcohol and other organic solvents, heterocyclic ring bearing aldehyde which condenses with amine to produce imine derivatives. Generally amine reacts with primary aromatic amine or aliphatic amine to form N-substituted products known as imine derivative and Schiffs base or azomethines reaction may be carried out by heating a mixture of amine and aldehyde in equal molar proportions alone or with a diluent or medium such as acetic acid or alcohol.[2]

In current study, a simple new method has been developed in which 2-thiophenecarboxaldehyde was used first time for derivatization of cefixime and simultaneous separation of three components i.e. Cefixime, 2-TCA and imine derivative was carried out in a very short time by HPLC–DAD. The LOD and LOQ of imine derivative were obtained within the range of 0.132–0.401 μg ml−1 consequently; these data were also compared with that of underivatized cefixime, and the results revealed the increased sensitivity and selectivity of derivative. The results were further confirmed by standard addition technique. Imine derivative was confirmed by comparison of peak height, retention time and spectral changes with cefixime drug and 2-Thiophenecarboxaldehyde reagent and also reconfirmed by extracting out from mixture using n-hexane solvent. Furthermore, HPLC method was validated according to ICH international guidelines which revealed that method was rapid, linear, accurate, sensitive precise, stability indicating and applicable for determination of imine derivative of cefixime.

Interaction of 2-thiophenecarboxaldehyde and its monohydrated complex

The rotational spectrum of 2-thiophenecarboxaldehyde was investigated by using supersonic jet Fourier transform microwave spectroscopy. The measurements were extended to the 34S, 33S, 13C, and 18O isotopologs for the cis conformer, as well as to the 34S and 13C isotopologs for the trans conformer, leading to an accurately structural determination of the two observed conformers. The unchanged experimental Pcc values upon isotopic substitution indicate effective planar geometries of the two conformers. The ring structures of thiophene are slightly different between the cis and trans conformers. Two isomers of the monohydrated complex of 2-thiophenecarboxaldehyde, formed between a cis or trans monomer with water stabilized by an O—H⋯O hydrogen bond (HB) and an additional (C=O)CH⋯O(H2O) or (Cring)CH⋯O(H2O) HB, respectively, were observed in jet expansion. The noncovalent interactions attributed to the stabilization of the monomer and the monohydrated complex are revealed by quantum chemical methods. The interaction energy for trans-w-1 is 4 kJ mol−1 larger than that of cis-w-1, attributed to the relative stronger CH⋯O HB. The relative abundance of the two conformers of the 2-thiophenecarboxaldehyde monomer and the two isomers of the complex was estimated in the jet.[3]

References

[1]Lee M, Shin M, Lee H. Coverage dependent variation of the adsorption structure of 2-thiophenecarboxaldehyde on the Ge(100)-2 × 1 reconstructed surface. Molecules. 2013 Aug 26;18(9):10301-11. doi: 10.3390/molecules180910301. PMID: 24064446; PMCID: PMC6270542.

[2]Maheshwari ML, Memon AA, Memon S, Memon FU, Mughal UU, Dayo A, Memon N, Ghoto MA, Khan Leghari M. Optimization of HPLC method for determination of cefixime using 2-thiophenecarboxaldehyde as derivatizing reagent: A new approach. Saudi Pharm J. 2015 Sep;23(4):444-52. doi: 10.1016/j.jsps.2015.01.016. Epub 2015 Jan 16. PMID: 27134548; PMCID: PMC4834682.

[3]Li, Wenqin et al. “Molecular structure and non-covalent interaction of 2-thiophenecarboxaldehyde and its monohydrated complex.” The Journal of chemical physics vol. 151,16 (2019): 164307. doi:10.1063/1.5126126

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