Direct Synthesis of Amides from Amines and Carboxylic Acids under Hydrothermal Conditions

Abstract

Hydrothermal systems provide a unique habitat for the subsurface biosphere, and possibly, for the origin of life. Amides are fundamental to hydrothermal organic geochemistry and deep subsurface biology research, in large part because of their involvement in metabolism, such as in the forms of peptides and proteins, and also because of their participation in the deep nitrogen cycle and their potential role in the origin of life. Hydrothermal chemistry of amides is also of great interest to astrobiology research because it may reveal potential formation pathways of peptides and biomolecules in the space outside Earth. Here, we describe a nonmineral-catalyzed synthetic pathway for amide synthesis under hydrothermal conditions (250 °C and 40 bar, P sat). We find that a suite of amides (12 examples) are readily synthesized through a direct condensation between amines and carboxylic acids, with an amide yield of up to 90% over a timescale of hours. Time-series hydrothermal experiments were performed to obtain apparent rate constants for amide synthesis. The observed hydrothermal rate constants were significantly larger for certain amines (e.g., 0.2 h–1 for benzylamine) than for others (e.g., 0.05 h–1 for cyclohexylamine), which suggests a strong substitution effect on amide formation. An amine acylation mechanism is proposed, and also consistent with previous studies. Furthermore, amide formation is found to be strongly inhibited in high or low pH solutions (e.g., pH <2 or >12), which further supports that the condensation reaction should occur between the neutral amine and acid. Our finding of a feasible and selective hydrothermal pathway for amide bond formation may provide new insights into understanding peptides and biomolecule synthesis in relevant hydrothermal environments.

Anaerobic oxidation of aldehydes to carboxylic acids under hydrothermal conditions

“…Hydrothermal experiments were conducted in sealed fused silica tubes under an aqueous condition of 200 C and 15 bar (P sat , calculated using SUPCRT92) 22 in the absence of O 2 , following a previously developed method. 17,23,24 We started our investigation by examining the oxidation of benzaldehyde (compound 1) under hydrothermal conditions using various Cu(II) and Fe(III) salts, including CuCl 2 , CuSO 4 , Cu(OAc) 2 , Cu(NO 3 ) 2 , FeCl 3 , Fe 2 (SO 4 ) 3 , and Fe(NO 3 ) 3 (Table 1). In pure water without additives, only 4% of benzaldehyde reacted at 200 C aer 24 h, forming benzoic acid with a yield of 3% (entry 1).…”

Impact of Phyllosilicates on Amino Acid Formation under Asteroidal Conditions

“…Two main reasons can be proposed for these observations. First, the formose and Maillard-like reactions compete with the nucleophilic addition of an amine to a CA to produce amides. − The formation of amides has been observed on non-targeted GC–MS analyses of HMT + CA experiments, reported in Supporting Information (see Supporting Information). Aliphatic amides are formed after two days of experiments (Figures SI4, SI5, Table SI4).…”

“…Two main reasons can be proposed for these observations. Firstly, the formose and Maillard-like reactions compete with the nucleophilic addition of an amine to a carboxylic acid to produce amides [60][61][62] . The formation of amides has been observed on non-targeted GC-MS analyses of HMT+CA experiments, reported in supplementary text (see SI).…”

Hydrothermal Transformations of Alcohols with Copper(II) and Iron(III) Salts

“…Hydrothermal experiments were conducted following protocols developed from previous work. ,, In short, liquid alcohols were injected into fused-silica glass tubes (6 mm OD and 2 mm ID) using a gas-tight microsyringe, and 0.3 mL of copper or iron salt solution (0.2 molal in deionized and deoxygenated water) was subsequently added. The final alcohol concentration in solution was made to be 0.1 molal.…”

“…Transformations of organic matter in Earth’s hydrothermal systems are relevant to many important geological processes, such as crude oil and petroleum formation, sedimentary organic transport and deposition, and deep carbon cycling in the oceanic crust. − Degradation of pre-existing organic matter and generation of new organic molecules under hydrothermal conditions could also provide food and energy for the deep biosphere. , Some remarkable and unexpected formation pathways of biomolecule precursors such as peptides and amides in hydrothermal fluids have been reported, − which could be relevant to prebiotic synthesis and origin-of-life processes on Earth and other habitable planetary environments . Among these hydrothermal organic transformations, the interconversions that link alkanes to carboxylic acids through alkenes, alcohols, and ketones/aldehydes (Scheme ) are of particular interest. ,, Identifying the pathways and mechanisms of these hydrothermal organic interconversions is thus critical to understand the origin and fate of organic compounds in the deep subsurface.…”