Elsevier

Journal of Molecular Structure

Volume 1049, 8 October 2013, Pages 149-156
Journal of Molecular Structure

Aromatic aldehyde-catalyzed gas-phase decarboxylation of amino acid anion via imine intermediate: An experimental and theoretical study

https://doi.org/10.1016/j.molstruc.2013.06.046Get rights and content

Highlights

  • Using MS/MS and DFT to study decarboxylation of amino acid anion catalyzed by aromatic aldehyde.

  • Decarboxylation of α-amino acid anion is determined by direct dissociation of adjacent Csingle bondC bond.

  • Dissociation of Csingle bondC bond is promoted by conjugation between α-carbon, Cdouble bondN bond and benzene ring.

  • Decarboxylation of non-α-amino acid anion proceeds via a SN2-like transition state.

  • Dissociation of Csingle bondC bond and attacking of carbanion to Cdouble bondN bond or benzene occur synchronously.

Abstract

It is generally appreciated that carbonyl compound can promote the decarboxylation of the amino acid. In this paper, we have performed the experimental and theoretical investigation into the gas-phase decarboxylation of the amino acid anion catalyzed by the aromatic aldehyde via the imine intermediate on the basis of the tandem mass spectrometry (MS/MS) technique and density functional theory (DFT) calculation. The results show that the aromatic aldehyde can achieve a remarkable catalytic effect. Moreover, the catalytic mechanism varies according to the type of amino acid: (i) The decarboxylation of α-amino acid anion is determined by the direct dissociation of the Csingle bondC bond adjacent to the carboxylate, for the resulting carbanion can be well stabilized by the conjugation between α-carbon, Cdouble bondN bond and benzene ring. (ii) The decarboxylation of non-α-amino acid anion proceeds via a SN2-like transition state, in which the dissociation of the Csingle bondC bond adjacent to the carboxylate and attacking of the resulting carbanion to the Cdouble bondN bond or benzene ring take place at the same time. Specifically, for β-alanine, the resulting carbanion preferentially attacks the benzene ring leading to the benzene anion, because attacking the Cdouble bondN bond in the decarboxylation can produce the unstable three or four-membered ring anion. For the other non-α-amino acid anion, the Cdouble bondN bond preferentially participates in the decarboxylation, which leads to the pediocratic nitrogen anion.

Introduction

Decarboxylation is a chemical reaction that releases carbon dioxide. Specifically, the loss of a carboxyl group is normally described as the direct conversion of its conjugate base, a carboxylate, to carbon dioxide and a carbanion, followed by protonation of the carbanion. Due to their importance, the reactions of this kind have received a great deal of attention in chemistry and biochemistry [1], [2], [3], [4], [5], [6], [7], [8], [9].

Amino acids play central roles both as building blocks of proteins and as intermediates in metabolism. Decarboxylation of the amino acids is one of the effective methods for obtaining a number of important amino compounds which are versatile substances in the synthesis of biologically active compounds [10], [11], [12], [13], [14]. Therefore, the investigation into the decarboxylation of the amino acids seems to be of great significance. Early research mainly focuses on the radical-induced decarboxylation of amino acids [15], [16], [17]. It is evident that this process is important for biological systems considering many well-established enzymatic or metabolic pathways of radical generation “in vivo”. Chemically, decarboxylation appears to be initiated by oxidative attack. Recently, carbonyl-induced decarboxylation of amino acids has attracted a lot of interest. Wolfenden’s group has reported the ability of acetone to promote the decarboxylation of 2-aminomalonate [18]. Of various methods available, the decarboxylation of tryptophan in the presence of ketone catalyst is the simplest way to the synthesis of tryptamine, which is a very important starting material in the synthesis of various indole alkaloids [13].

Certain progress has been made in the carbonyl-catalyzed decarboxylation of amino acids, however, to the best of our knowledge, most of the investigations concentrate in the liquid reactions. The rate of the decarboxylation is determined by the catalyst and pH value of the solution. However, the carbonyl-catalyzed decarboxylation of amino acids in the gas phase has received considerably less attention. This makes us decide to explore the gas-phase decarboxylation reactions of the amino acids with the assistance of aromatic aldehyde from both experimental and computational perspective, as is shown in Scheme 1. α-Amino acids, such as l-alanine l-phenylalanine and etc, and non-α-amino acids, such as β-alanine, γ-aminobutyric acid and ε-aminocaproic acid, have been selected as the object of study. Herein, two items should be emphasized. First, as this work focuses on the gas-phase decarboxylation of amino acid anion via imine intermediate, only aromatic aldehyde has been selected as the catalyst. The reason is that the use of aliphatic aldehyde probably leads to the problem of obtaining additional intermediates (enamines) which would complicate the mechanistic study of the reactions involved. Secondly, the tandem mass spectrometry in the negative ion mode has been used to study the decarboxylation of the amino acid anion.

It is well known that the Cdouble bondN bond widely exists in the organocatalyses [19], [20], [21], because the formation of the Cdouble bondN bond can effectively increase the electrophilicity of the corresponding carbonyl. In this paper, the influence that the Cdouble bondN bond and benzene ring exert on the dissociation of the Csingle bondC bond adjacent to the carboxylate and the nature of the decarboxylation will be explored by tandem mass spectrometry technique and DFT calculations.

Section snippets

Material

l-alanine, l-phenylalanine, β-alanine, γ-aminobutyric acid, ε-aminocaproic acid, benzaldehyde, cinnamaldehyde, 4-methoxybenzaldehyde and 4-(dimethylamino)-benzaldehyde were obtained from the Sigma-Aldrich Company. These chemical reagents with >95% purity have been used without further purification.

Mass spectrometry

The mass spectral data were acquired on a LCQ ion trap mass spectrometer from ThermoFinnigan (San Jose, CA, USA) equipped with an electrospray ionization (ESI) interface operated in the negative ion

Results and discussion

Several typical amino acids have been selected as the objects of the investigation. Thereinto, l-alanine and l-phenylalanine represent α-amino acids, while non-α-amino acids contain β-alanine, γ-aminobutyric acid and ε-aminocaproic acid. The examination of the direct decarboxylation of these amino acid anions without any catalyst has been performed first. The deprotonated amino acids can be prepared by electrospray ionization of a 3:1 (v/v) acetonitrile/water solution containing these amino

Conclusions

On the basis of the tandem mass spectrometry (MS/MS) technique and DFT calculations, the present paper has carried out the experimental and theoretical investigation into the decarboxylation of the amino acid anion catalyzed by the aromatic aldehyde. The following conclusions can be made from our results:

  • 1.

    Whether for α-amino acid or non-α-amino acid anion, both MS/MS experiments and DFT calculations show that the aromatic aldehyde can effectively promote its decarboxylation.

  • 2.

    The decarboxylation

Acknowledgement

The author gratefully acknowledges financial support from the start-up costs to introduce research personnel of Zhejiang Gongshang University (1110XJ2010044, 1110XJ2110044).

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