Formamide Dehydration Research Articles

Nucleophilic Cyanation of Enones and Imines with Formamide as the Cyano Source

AbstractA convenient cyano source for the nucleophilic 1,4‐addition to enones and 1,2‐addition to imines has been developed, by generating the cyano unit in situ. via the TCT‐assisted dehydration of formamide. This protocol distinguishes itself by transition‐metal/ligand free conditions, compatibility with 1,4‐/1,2‐addition, readily available substrates and versatile synthetic utilities of the cyanated products.

A More Sustainable Isocyanide Synthesis from N-Substituted Formamides Using Phosphorus Oxychloride in the Presence of Triethylamine as Solvent.

A simple, green, and highly efficient protocol for the synthesis of isocyanides is described. The reaction involves dehydration of formamides with phosphorus oxychloride in the presence of triethylamine as solvent at 0 °C. The product isocyanides were obtained in high to excellent yields in less than 5 min. The method offers several advantages including increased synthesis speed, relatively mild conditions, and rapid access to large numbers of functionalized isocyanides, excellent purity, increased safety, and minimal reaction waste. The new approach of synthesising dehydrative isocyanides from formamides is significantly more environmentally-friendly than prior methods.

Ni-Mediated Generation of “CN” Unit from Formamide and Its Catalysis in the Cyanation Reactions

The in situ generation of a “cyano” unit from readily available organic precursors is of high interest in synthetic chemistry. Herein, we report the first example of Ni-mediated dehydration of formamide to form “CN” and its subsequent catalytic applications in the hydrocyanation of alkynes and cyanation of aryl halides. Formamide can serve as a convenient source for the nitrile unit, in that it releases water as the only byproduct.

Synthesis of isocyanides through dehydration of formamides using XtalFluor-E

The formation of isocyanides from formamides using XtalFluor-E, [Et2NSF2]BF4, is presented. A wide range of formamides can be used to produce the corresponding isocyanides in up to 99% yield. In a number of cases, the crude products showed good purity (generally >80% by NMR) allowing to be used directly in multi-component reactions.

Decomposition Pathways of the Neutral and Protonated Formamide in Some Lower-Lying Excited States

Unimolecular decompositions of neutral (NH2CHO) and protonated (NH3CHO(+)) formamide, an active precursor of biomolecules in prebiotic chemistry, are investigated in the ground (S0) and first triplet (T1) and singlet (S1) excited states. Different decomposition channels including the homolytic bond dissociations, dehydration, decarbonylation, dehydrogenation, etc., are explored using coupled-cluster theory (CCSD(T)/CBS method) for both S0 and T1 states and RASPT2(18,15)/6-31G(d,p) computations for the S1 state. On S1 and T1 energy surfaces, formamide preferentially follows C-N homolytic bond cleavages forming NH2 + HCO radical pairs. Formation of HCN and HNC from dehydration of neutral and protonated formamide via formimic acid and aminohydroxymethylene isomers has higher energy barriers. A strong stabilization upon triplet excitation of the two latter isomers significantly facilitates the interconversions between isomers, and thus considerably reduces the energy barriers for dehydration pathways. The most probable pathways for HCN and HNC generation are found to be dehydration of formamide in the T1 state. Dehydration pathways from the neutral S1 and protonated T1 forms lead to stable complexes of HCN and HNC with water but are associated with large energy barriers. Overall, in the lower-lying excited states of either neutral or protonated formamide, dehydration is not competitive with homolytic C-N bond cleavages, which finally lead to formation of CO.

One-pot preparation of isocyanides from amines and their multicomponent reactions: crucial role of dehydrating agent and base

A novel one-pot practical approach for the preparation of isocyanide directly from amine and its reaction has been developed. It employs formylation of amine, dehydration of formamide to isocyanide, and its multicomponent reactions (Ugi, Passerini, and Groebke–Blackburn–Bienaymé reactions). This method provides a significant solution to known synthetic difficulties of isocyanides. In this approach, the nature and stoichiometric quantities of dehydrating agent and base, and the catalysis-function of by-products were found to play crucial roles.

ChemInform Abstract: Catalytic Cooperation Between MoO3 and Sb2O4 in N-Ethyl Formamide Dehydration. Part 3. Comparison of a Mathematical Model Based on the Remote Control Mechanism with Experimental Results.

ChemInform Abstract: Catalytic Cooperation Between MoO3 and Sb2O4 in N-Ethyl Formamide Dehydration. Part 3. Comparison of a Mathematical Model Based on the Remote Control Mechanism with Experimental Results.

ChemInform Abstract: Catalytic Cooperation Between MoO3 and Sb2O4 in N-Ethyl Formamide Dehydration. Part 2. Nature of Active Sites and Role of Spillover Oxygen.

ChemInform Abstract: Catalytic Cooperation Between MoO3 and Sb2O4 in N-Ethyl Formamide Dehydration. Part 2. Nature of Active Sites and Role of Spillover Oxygen.

Multicomponent Reactions of Convertible Isonitriles

A new family of unsaturated isonitriles has been prepared by the base-promoted ring-opening of oxazoles, offering an alternative to the conventional formamide dehydration route. These compounds undergo the full complement of multicomponent reactions for which isonitriles are known and offer the desirable trait of giving amide products that readily participate in acyl substitution reactions (hence, they are convertible). Moreover, they do not have the objectionable odors for which isonitriles are typically known, making them more accessible as reagents for organic synthesis. One focus of the work is isonitriles bearing perfluorinated alkyl groups that enable the ready separation of such reagents from nonfluorinated reaction products using the "light" fluorous method of fluorous solid-phase extraction.

Oxalyl Chloride: A Versatile Reagent in Organic Synthesis

Oxalyl chloride is a very versatile reagent extensively used by organic chemists. One of its most common uses is in oxidation of alcohols to aldehydes and ketones named Swern oxidation. [1-5] However, this reagent can efficiently be applied in many other reactions such as 1,1-cycloadditions with 1,4-dilithio-1,3-dienes or zirconacyclopentadienes, [6] cyclization of 1,3-bis(trimethylsilyloxy) alk-1-enes to isoeletronic acids, [7] preparation of phenyl isocyanates from anilines, [8] bicyclization of biaryl acetamides, [9] dehydration of formamides to afford nitriles, [10] and ­cyclization of 1,1-bis(trimethylsilyloxy) ketene acetals to give 3-hydroxymaleic anhydrides. [11]

Microwaves, supported-reagents and parallel synthesis: isocyanide and ester synthesis.

The benefits of microwave irradiation are described for a number of important reactions such as amid and ester formation and dehydration of formamide to the corresponding isonitriles. Not only were reaction times dramatically reduced but the transformations were less prone to side reactions and decomposition.

Dehydration of formamides using the Burgess Reagent: a new route to isocyanides

The Burgess Reagent readily converts formamides into isocyanides in high yields and is particularly effective for substrates containing halide sensitive trimethylsilyl ether groups.

ChemInform Abstract: Catalytic Cooperation Between MoO3 and Sb2O4 in N‐Ethyl Formamide Dehydration. Part 1. Preparation, Characterization, and Catalytic Results.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Catalytic cooperation between MoO 3 and Sb 2O 4 in N-ethyl formamide dehydration III. Comparison of a mathematical model based on the remote control mechanism with experimental results

We present a mathematical model of the remote control effect in the cooperation between α-Sb 2O 4 (spillover oxygen donor) and MoO 3 (acceptor and catalytic phase) in the oxygen assisted dehydration of formamides. The model is compared with experimental results obtained with 21 mechanical mixtures of α-Sb 2O 4 and MoO 3 of different compositions, at 3 different reaction temperatures, and oxygen partial pressure varying over a range of more than 2 orders of magnitude. The observed increase of activity of MoO 3 due to the effect of the remote control corresponds extremely well (variance of squared residue better than 3 × 10 −3) to the results of the mathematical model. We have verified that the magnitude of the kinetic parameters and surface concentration of spillover oxygen is physically acceptable, and that the variations of these parameters with the temperature correspond to those predicted by the general laws of physical chemistry.

Catalytic cooperation between MoO 3 and Sb 2O 4 in N-ethyl formamide dehydration I. Preparation, characterization, and catalytic results

Catalysts containing MoO 3 and α-Sb 2O 4 with different “architectures” were prepared by different methods: mixing of separately prepared pure oxides, impregnation of MoO 3 by Sb 2O 4 or vice versa. We report results obtained in the oxygen-aided dehydration of N-ethyl formamide catalyzed by these solids. A strong synergy between Mo and Sb is always observed. Extensive characterization of the catalysts before and after catalytic test, by X-ray diffraction, Electron Microscopy, Analytical Electron Microscope, XPS, and Ion Scattering Spectroscopy excludes the formation of mixed oxides or solid solutions as well as mutual contamination. Rather, the artificial contamination created by impregnation with a precursor of the other oxide exhibits a strong tendency to disappear. The catalytic synergy persists after the contamination has disappeared. The origin of the observed synergy is attributed to a remote control mechanism, namely spillover oxygen produced by α-Sb 2O 4 creates and/or regenerates active and selective sites on MoO 3.

Catalytic cooperation between MoO 3 and Sb 2O 4 in N-ethyl formamide dehydration II. Nature of active sites and role of spillover oxygen

The present work reports experiments designed to further investigate the role of MoO 3 and Sb 2O 4 in the cooperative effect they exhibit in N-ethyl formamide dehydration. Temperature-programmed desorption of NH 3 showed that Bronsted acid sites are responsible for activity. TPD of CO 2 gave no indication of basic sites. The Brønsted sites are sensitive to reduction and reoxidation. Thermoreoxidation of previously reduced molybdenum oxide and oxidation of carbon deposited on MoO 3 are more rapid when α-Sb 2O 4 is admixed. The interpretation of the phenomenon is that α-Sb 2O 4 dissociates molecular O 2 to an oxygen spillover species which can maintain MoO 3 at a high degree of oxidation and, if necessary, reoxidize it or remove deposited carbon. Brønsted sites necessitate a high degree of oxidation and their number is consequently promoted by spillover oxygen. Mechanisms are proposed for the dissociation of oxygen, the reoxidation of pre-reduced MoO 3, and the formation of Brønsted acid sites. The importance of the reported results for selective oxidation or multicomponent catalysts is discussed.

Conjugated N-isocyanides; a reassessment and a correction of claimed stable conjugated N-isocyanides. Stable N-formyltriazenes; a confirmation

Previously claimed stable solid aryldiazoisocyanides were found to be crude arylazides, and dehydration of formamides as a route to stable N-isocyanides must be viewed with caution; stable N-formyltriazenes are confirmed and literature difficulties with reproducible syntheses are explained.

Two-phase catalysts in selective oxidation and related reactions

Catalytic properties of mechanical oxide mixtures : Sb 2O 4 + MoO 3 and TiO 2 + V 2 O 5 have been studied in two reactions : N-ethyl formamide dehydration and isobutylene oxidation. An interpretation of the results obtained is proposed on the basis of the remote control concept and an hypothesis about the junction between two cooperating phases.

ChemInform Abstract: Formamide as a Precursor to Cyanide in Mixed‐valence Copper(I,II) Cyanide Complexes.

AbstractThe dehydration of formamide by acetic anhydride forms hydrogen cyanide which reacts with Cu(I) acetate (II) to give simple cyano‐complexes of Cu(I), (I) or (III), and with Cu(II) acetate (V) to produce either a Cu(I) complex (IV) or a mixed‐valence compound (VI), depending on the solvent used.

Catalytic synergy between MoO 3 and BiPO 4 in N-ethyl formamide dehydration : I. Catalytic properties, reducibility, and reoxidizability of mixtures of MoO 3 and BiPO 4

In previous publications, we reported that a catalyst composed of BiPO 4 and MoO 3 is active in the dehydration of formamides to nitriles. Some molecular oxygen in the feed is necessary for maintaining the catalyst active and selective. We report here results obtained with catalysts of different compositions prepared by mixing, by three different methods, separately prepared powders of BiPO 4 and MoO 3. The mixtures are more active than the single components. They are reduced more easily under a high vacuum or in the presence of oxygen and they reoxidize subsequently more rapidly. A decrease of the oxygen pressure, during catalysis, depresses the magnitude of the synergetic effect, changing more the activity of the MoO 3-rich mixtures. The possible interpretations of the synergy are discussed. It is concluded that the synergy could be due to a remote control mechanism, whereby BiPO 4 probably produces a mobile oxygen species which, by spill-over onto MoO 3, restores catalytically active centers on this latter. The effects observed in reduction experiments are explained by a reverse spill-over.