Photo-on-Demand Synthesis of Vilsmeier Reagents with Chloroform and Their Applications to One-Pot Organic Syntheses

Abstract

The Vilsmeier reagent (VR), first reported a century ago, is a versatile reagent in a variety of organic reactions. It is used extensively in formylation reactions. However, the synthesis of VR generally requires highly toxic and corrosive reagents such as POCl 3 , SOCl 2 , or COCl 2 . In this study, we found that VR is readily obtained from a CHCl 3 solution containing N,Ndimethylformamide or N,N-dimethylacetamide upon photoirradiation under O 2 bubbling. The corresponding Vilsmeier reagents were obtained in high yields with the generation of gaseous HCl and CO 2 as byproducts to allow their isolations as crystalline solid products amenable to analysis by X-ray crystallography. With the advantage of using CHCl 3 , which bifunctionally serves as a reactant and a solvent, this photo-on-demand VR synthesis is available for one-pot syntheses of aldehydes, acid chlorides, formates, ketones, esters, and amides.

Reactivity and Product Selectivity of Fluoroalkyl Carbonates in Substitution Reactions with Primary Alcohols and Amines

“…We previously reported an in situ photo-on-demand phosgenation reaction with CHCl 3 and O 2 (Scheme ). − This reaction allowed easy and safe syntheses of aryl and haloalkyl carbonates in high yields simply upon UV irradiation of CHCl 3 solutions containing a mixture of the corresponding alcohol, having a lower p K a value than alkyl carbonates, and an organic base under O 2 bubbling . Using this photochemical reaction, in the present study, we prepared a series of symmetric and unsymmetric haloalkyl carbonates, as shown in Scheme and Table , respectively.…”

Photo-On-Demand Synthesis of α-Amino Acid N-Carboxyanhydrides with Chloroform

“…In support of this proposed mechanism, commercially available l -Phe·HCl was found to provide the corresponding NCA in 70% yield (Table , entry 1I). Thus, the reaction takes a longer time at higher temperature compared with other phosgenation reactions reported previously. − For safe handling of the reaction, the generated amount of COCl 2 should be regulated by ON–OFF cycles and/or intensity of the photo-irradiation, and the vaporized COCl 2 and generated HCl must be trapped with alcohol and alkaline water.…”

“…Contrarily, other chlorocarbons such as CCl 4 and CH 2 Cl 2 produced less amounts of COCl 2 through similar photochemical reactions. The reaction with CHCl 3 could be applied to a variety of in situ phosgenation reactions like with BTC. − Compared with BTC, CHCl 3 is an inexpensive and more abundant compound capable of being used as a solvent. Further, the reaction allows photo-on-demand control of phosgenation reactions without using the chemical additives.…”

Photo-on-Demand Phosgenation Reactions with Chloroform for Selective Syntheses of N-Substituted Ureas and Isocyanates

“…We previously reported that CHCl 3 undergoes oxidative photodecomposition under exposure to UV light to efficiently produce COCl 2 (Scheme ). Recently, we then successfully developed in situ photo-on-demand phosgenation reactions. − As a representative example, a CHCl 3 solution containing a mixture of an alcohol and an organic base such as pyridine upon exposure to UV-C light provided carbonate esters in high yield via the chloroformate as an intermediate . Although it is known that the alcohol serves as a stabilizer to decelerate the decomposition of CHCl 3 , and further, that the organic base absorbs UV light, , the phosgenation reaction occurred to give the product through an in situ base-catalyzed reaction of the alcohol and COCl 2 generated by the oxidative photodecomposition of CHCl 3 .…”