Carbamoyl Azides Research Articles

A Mild Metal‐Free Approach for the Direct Synthesis of Carbamoyl Azides from Carboxylic Acid Redox Active Esters

AbstractCarbamoyl azide is a pivotal compound used in the transformation into urea and amines, as well as in nitrene insertion reactions. In this study, we present a pioneering method for synthesizing carbamoyl azide directly from acid redox active esters without the use of metals or oxidants. This approach demonstrates tolerance for various functional groups, enhancing its applicability. Furthermore, this technique facilitates late‐stage modifications of natural products and pharmaceuticals, thereby accelerating the development and identification of novel drug candidates.

One‐Pot Conversion of Benzyl Alcohols to N‐Protected Anilines and Alkyl Alcohols to Carbamoyl Azides

AbstractOne‐pot, scalable procedures converting benzylic or aliphatic alcohols to various N‐functionalized amines are reported in 38–83 % overall yields. These multi‐step conversions are relatively economic and involve the oxidative formation of acid chloride intermediates and the Curtius rearrangement of acyl azides. Notable aspects of economy include: (1) the use of a relatively green solvent (chlorobenzene) that tolerates both ionic and radical reactions, without the need for rigorously dry or O2‐free conditions; (2) the use of minimal amounts of trichloroisocyanuric acid (TCCA) as a cheap and green chlorinating agent to oxidize the alcohol starting materials and then transform the aldehyde intermediates to acid chlorides under photoirradiation for azide addition; (3) the efficient capture of isocyanate intermediates by alcohol or azide nucleophiles providing N‐protected anilines or N‐protected alkylamines, respectively, the latter of which was employed in the synthesis of an anti‐dementia drug, memantine hydrochloride, over two purification steps.

Rhodium-Catalyzed Intramolecular Nitrogen Atom Insertion into Arene Rings.

In this study, we describe the direct insertion of an intramolecular nitrogen atom into an aromatic C-C bond. In this transformation, carbamoyl azides are activated by a Rh catalyst and subsequently directly inserted into the C-C bond of an arene ring to access fused azepine products. This transformation is challenging, owing to the existence of a competitive C-H amination pathway. The use of a paddlewheel dirhodium complex Rh2(esp)2 effectively inhibited the undesired C-H insertion. Density functional theory calculations were performed to reveal the reaction mechanism and origin of the chemoselectivity of the Rh-catalyzed reactions. The novel fused azepine products are highly robust and allow for downstream diversification.

Synthesis of Carbamoyl Azides from Redox-Active Esters and TMSN3

AbstractAn efficient method for construction of C–N bonds is reported here. The iron-catalyzed azidation of N-hydroxy phthalimide (NHP) esters provides a convenient approach for the synthesis of carbamoyl azides with good substrate scope and functional group tolerance. Both aryl carbon C(sp2) and alkyl carbon C(sp3) sources can be used deliver the carbamoyl azides. Mechanistic studies were conducted and a two-stage process was identified.

Synthesis of Carbamoyl Azides and 1-Substituted Tetrazol-5-ones from Isocyanates and NaN3 in the Presence of ZnCl2

Synthesis of Carbamoyl Azides and 1-Substituted Tetrazol-5-ones from Isocyanates and NaN3 in the Presence of ZnCl2

Access to Cyclic N-Trifluoromethyl Ureas through Photocatalytic Activation of Carbamoyl Azides.

We report the mild activation of carbamoyl azides to the corresponding nitrenes using a blue light/[Ir]-catalyzed strategy, which enables stereospecific access to N-trifluoromethyl imidazolidinones and benzimidazolones. These novel structural motifs proved to be highly robust, allowing their downstream diversification. On the basis of our combined computational and experimental studies, we propose that an electron rebound with the excited metal catalyst is undergone, involving a reduction-triggered nitrogen loss, followed by oxidation to the corresponding carbamoyl nitrene and subsequent C-H insertion.

Synthesis of carbamoyl azides via the Lossen rearrangement utilizing diphenyl phosphorazidate

A novel method was developed for the synthesis of carbamoyl azides from hydroxamic acids via the Lossen rearrangement using diphenyl phosphorazidate, which acts as both the activator and azide source to produce the azides via an isocyanate intermediate. Using this method, various hydroxamic acids were converted into the corresponding carbamoyl azides, enabling their preparation without the use of highly explosive reagents.

Ir-Catalyzed C-H Amidation Using Carbamoyl Azides for the Syntheses of Unsymmetrical Ureas.

An iridium-catalyzed C-H amidation for the syntheses of unsymmetrical urea was developed using carbamoyl azides (R(R')N-C(O)-N3) as the nitrogen source. A combination of iridium and silver gave an active catalyst for C-N bond formation. A variety of urea derivatives were synthesized using carbamoyl azides with only dinitrogen byproducts. Finally, the use of the transient directing group strategy with carbamoyl azides extended the substrate scope of the catalytic C-H amidation to yield aldehyde-containing unsymmetrical ureas.

Copper-Catalyzed Nitrogenation of Aromatic and Aliphatic Aldehydes: A Direct Route to Carbamoyl Azides

An efficient copper-catalyzed synthesis of carbamoyl azides directly from aldehydes has been developed. Both aromatic aldehydes and aliphatic aldehydes, together with other commercially available reactants, can be used as substrates in this radical relay reaction. Broad substrate scope, simple operation, readily available reagents, and good functionality tolerance make this method very attractive.

KI Catalyzed Nitrogenation of Aldehydes and Alcohols: Direct Synthesis of Carbamoyl Azides and Ureas

AbstractAn efficient KI catalyzed nitrogenation of aldehydes and alcohols for the direct synthesis of carbamoyl azides and ureas via a radical process has been developed. The simple operating procedures, the readily available starting materials including aldehydes, alcohols and amines, as well as the utility of the products all make this strategy very attractive.

One-Pot Synthesis of Carbamoyl Azides via Palladium-Catalysed Azidocarbonylation of Haloarenes Using N-Formylsaccharin as a CO Surrogate

A highly efficient one-pot synthesis of carbamoyl azides from haloarenes and sodium azide has been developed. The protocol involves palladium-catalysed azidocarbonylation of haloarenes utilizing N-formylsaccharin as a CO source to form acyl azides, which undergo in situ Curtius rearrangement to afford the desired carbamoyl azides. N-Formylsaccharin is an easy-to-handle solid alternative to CO gas.

N-Isocyanates, N-Isothiocyanates and Their Masked/Blocked Derivatives: Synthesis and Reactivity

In contrast to <i>C</i>-substituted isocyanates which are frequently used reagents in synthesis, nitrogen-substituted isocyanates (<i>N</i>-isocyanates) remained a scientific curiosity in the literature for over a century. The amphoteric character of these reactive intermediates, which results in their propensity to dimerize, prevented the development of their full synthetic potential. In this review, the pioneering work that led to the development of reliable methods for their synthesis, established the existence of such species by spectroscopy, and allowed a delineation of their basic reactivity is presented. The high reactivity of these intermediates has been controlled through the use of masked precursors to regulate their concentration via a reversible equilibrium, a strategy which is also used in industrial processes utilizing <i>C</i>-isocyanates. This control led to the development of more complex reactions, including reaction cascades that allow the rapid synthesis of heterocycles possessing the N–N–C=O motif, which is widely present in agrochemicals and pharmaceuticals. This review covers the literature of <i>N</i>-isocyanates and their sulfur analogues, <i>N</i>-isothiocyanates, until April 2016. 1 Introduction 2 Formation of <i>N</i>-Isocyanates 2.1 Rearrangement of Carbamoyl Azides 2.2 Ring Opening of Heterocycles 2.3 Thermolysis of Hydrazine Derivatives 3 Formation of <i>N</i>-Isothiocyanates 4 Isolation and Observation 4.1 Isolation and Observation of <i>N</i>-Isothiocyanates 4.2 Isolation and Observation of <i>N</i>-Isocyanates 5 Reactivity 5.1 Reactivity of <i>N</i>-Isothiocyanates 5.2 Reactivity of <i>N</i>-Isocyanates 6 Conclusion

ChemInform Abstract: Visible Light Induced Azidation of Aldehydic C—H with Carbon Tetrabromide and Sodium Azide.

AbstractThe protocol utilizes visible light as an inexpensive and sustainable energy source and is also applicable to a convenient one‐pot synthesis of carbamoyl azides starting directly from aldehydes.

Visible light induced azidation of aldehydic C–H with carbon tetrabromide and sodium azide

A convenient and highly efficient synthesis of acyl azides via visible light induced azidation of aldehydic C–H with carbon tetrabromide and sodium azide is reported. The approach is also, applicable to a one-pot synthesis of carbamoyl azides starting directly from aldehydes. Operational simplicity, good to excellent yields and utilization of visible light as an inexpensive and sustainable energy source are the salient features of the present protocol.

Direct Observation of Carbamoylnitrenes.

As the prototype Curtius rearrangement reaction, carbamoyl azide decomposes into aminoisocyanate and molecular nitrogen. However, the key intermediate carbamoylnitrene was previously undetected, even though the decomposition of carbamoyl azides has been studied frequently since its discovery in the 1890s. Upon ArF laser (λ=193 nm) photolysis, the stepwise decomposition of the two simplest carbamoyl azides H2 NC(O)N3 and Me2 NC(O)N3, isolated in solid noble gas matrices, occurs with the formation of the corresponding carbamoylnitrenes H2 NC(O)N and Me2 NC(O)N. Both triplet species are characterized for the first time by combining matrix-isolation IR spectroscopy and quantum-chemical calculations. Subsequent visible-light irradiations cause efficient rearrangement of these nitrenes into the respective aminoisocyanates.

Ceric Ammonium Nitrate (CAN) Catalyzed Modification of Ketones via Two C–C Bond Cleavages with the Retention of the Oxo-Group

A simple ceric ammonium nitrate (CAN) catalyzed functionalization of ketones through double C-C bond cleavage strategy has been disclosed. This reaction provides a mild, practical method toward carbamoyl azides, which are versatile intermediates and building blocks in organic synthesis. Based on relevant mechanistic studies, a unique and plausible C-C bond and N-O bond cleavage process is proposed, where the oxyamination intermediate plays an important role in this reaction.

Sodium Borohydride Reduction of Carbamoyl Azide Function: A Synthesis of N‐Protected N′‐Formyl‐gem‐diaminoalkyl Derivatives

AbstractA simple, efficient two‐step synthesis of N‐protected N′‐formyl‐gem‐diaminoalkyl derivatives is reported. The procedure involves the unprecedented reduction of the carbamoyl azide of α‐N‐Boc/Fmoc/Z‐protected amino acids and dipeptides (Boc = tert‐butoxycarbonyl, Fmoc = 9‐fluorenylmethoxycarbonyl, Z = benzyloxycarbonyl) by treatment with NaBH4 at room temperature. The reaction proceeds rapidly (45 min) without detectable epimerization (by HPLC‐ESI‐MS analysis) and is not influenced by the nature of the starting carbamoyl azide. The 1H and 13C NMR analyses of the synthesized N‐protected N′‐formamides were carried out in [D6]DMSO. The spectra exhibited the presence of two rotameric forms in solution as a result of the restricted rotation around the N–CO formyl bond. The integration of the N–CH–N protons of the two isomers showed that the cis isomer (rotamer B) was the more abundant conformer by 60 to 78 %. The reported synthesis represents the potential value of carbamoyl azides as versatile chiral starting materials for many synthetic purposes.

ChemInform Abstract: Dramatic Solvent Effect in the One‐Pot Synthesis of Substituted Ureas Directly from Primary Alcohols Using the Combined Reagent of Iodobenzene Dichloride and Sodium Azide in Ethyl Acetate.

AbstractCompare to MeCN, previously used in similar procedures, ethyl acetate is found to be the optimal solvent for the conversion of benzylic alcohols into carbamoyl azides.

Dramatic Solvent Effect in the One-Pot Synthesis of Substituted Ureas Directly from Primary Alcohols Using the Combined Reagent of Iodobenzene Dichloride and Sodium Azide in Ethyl Acetate

A highly efficient and practical method for the synthesis of substituted ureas directly from various primary alcohols and amines has been developed. This method is based on the finding that the use of ethyl acetate as the solvent can result in an improved efficiency of the transformation of various primary alcohols to their corresponding carbamoyl azides with the combined reagent of iodobenzene dichloride (PhICl₂) and sodium azide.

Silicon-mediated Direct Conversion of Acyl Chlorides to Carbamoyl Azides or/and Tetrazolinones under Mild Conditions

Abstract A simple and mild one-pot procedure for the synthesis of carbamoyl azides from acyl chlorides utilizing a combination of tetrachlorosilane and sodium azide in acetonitrile at ambient temperature is reported. Under gentle heating, 1-aryltetrazolin-5-ones were also obtained in one-pot process presumably via a [3 + 2] cycloaddition step.