A General Catalytic Method for Highly Cost‐ and Atom‐Efficient Nucleophilic Substitutions

Abstract

A general formamide-catalyzed protocol for the efficient transformation of alcohols into alkyl chlorides, which is promoted by substoichiometric amounts (down to 34 mol %) of inexpensive trichlorotriazine (TCT), is introduced. This is the first example of a TCT-mediated dihydroxychlorination of an OH-containing substrate (e.g., alcohols and carboxylic acids) in which all three chlorine atoms of TCT are transferred to the starting material. The consequently enhanced atom economy facilitates a significantly improved waste balance (E-factors down to 4), cost efficiency, and scalability (>50 g). Furthermore, the current procedure is distinguished by high levels of functional-group compatibility and stereoselectivity, as only weakly acidic cyanuric acid is released as exclusive byproduct. Finally, a one-pot protocol for the preparation of amines, azides, ethers, and sulfides enabled the synthesis of the drug rivastigmine with twofold S 2 inversion, which demonstrates the high practical value of the presented method.

Formamide Catalysis Facilitates the Transformation of Aldehydes into Geminal Dichlorides

“…entry catalyst loading yield 1a (1) [%] yield 2a (1) [%] lab journal no. Nevertheless, in comparison to the previous protocols of our group for the transformation of alcohols into alkyl chloride with BzCl and TCT, respectively, [2,3] the difference in performance of FPyr and DMF is relatively marginal. As the concentration of substrate 11 with 2 mol/L (= 2 M) was already high and the yields obtained for compound 21 were around 90%, no optimization of the solvent amount was persued.…”

Lewis Base Catalysis Enables the Activation of Alcohols by means of Chloroformates as Phosgene Substitutes

“…According to our previous method [6a] the utilization of BzCl instead of PCF gave 4 a in an enhanced yield of 90 %, which is comparable to the yields accomplished after reaction with PCF after 20 h (see above). However, chloride 4 a emerged from the reaction of 1 a with TCT [6b] in a clearly mitigated yield of 50 %.…”

“…While the syntheses of benzylic and allylic chlorides were conducted at room temperature (Scheme 3 B ), less reactive aliphatic starting materials required heating to 80 °C (Scheme 3 D ). The elevated reaction temperatures T are needed to allow for a catalytic turn‐over [6a,b] . Whereas THF had been realized as optimal solvent for benzylic and allylic alcohols (see Scheme 2 D ), transformations of aliphatic substrates were carried out preferentially in 1,4‐dioxane due to its higher boiling point.…”

A C−N Coupling Polymerization on Ice‐Surface towards Decimeter‐Sized 2D Covalent Materials with High Catalytic Activity for Water‐Splitting

“…After survey, the C−N coupling reaction between arylamines and cyanuric chloride was focused on, because its reactants can be separated into H 2 O (arylamine and base) and organic phases (cyanuric chloride). Moreover, as polymerization between p ‐phenylenediamine and cyanuric chloride in homogenous solutions under room temperature which yields irregular powders has been reported (Figure d), this C−N coupling reaction may also occur at freezing temperature . If so, different from above oxidation polymerizations, it is possible to synthesize 2D covalent materials on ice‐surface since functionality of its monomers can be more than two (Figure e).…”

“…Moreover,a sp olymerizationb etween p-phenylenediaminea nd cyanuric chloride in homogenouss olutions under room temperature which yields irregular powders has been reported( Figure 1d), [11] this CÀNc oupling reaction may also occur at freezing temperature. [12] If so, different from above oxidationp olymerizations, it is possible to synthesize 2D covalent materials on ice-surface since functionality of its monomers can be more than two (Figure1e).…”