Facile and Selective Synthesis of Chloromethylpyridines and Chloropyridines Using Diphosgene/Triphosgene

Solvent-Free or Low-Solvent Large-Scale Preparation of Chloropyrimidine and Analogues

“…2-Chloropyridine (5): reaction scale 1.3 mol; yield 127.5 g (90%, distillation 165 – 173 °C); purity 96.8% (by HPLC, wavelength 230 nm). Spectroscopic data matched literature reported data: 1 H NMR and MS. , …”

“…2-Chloropyridine (5): reaction scale 1.3 mol; yield 127.5 g (90%, distillation 165 À 173 °C); purity 96.8% (by HPLC, wavelength 230 nm). Spectroscopic data matched literature reported data: 1 H NMR and MS. 27,28 2,4-Dichloro-5-methoxypyrimidine (2). To a 50 L ceramic reactor was first added 6.8 L of pyridine (84.5 mol), followed by 12 kg (84.5 mol) of 2,4-dihydroxy-5-methoxypyrimidine.…”

Nucleophilic Halogenation of HeterocyclicN‐Oxides: Recent Progress and a Practical Guide

“…Meisenheimer [6a] and Bobrański [6b,c] observed the formation of chlorinated pyridines and quinolines upon heating of the corresponding N ‐oxides with SO 2 Cl 2 . Given the importance of this reaction for the synthesis 2‐halogenated heteroaromatic systems, numerous methods utilizing different electrophilic agents and halogen sources have been developed, in particular based on phosphorus halides (POCl 3 , [7] POCl 3 /PCl 5 , [8] POBr 3 , [9] PCl 3 , [10] PBr 3 , [9a,10b,11] ethyl phosphorodichloridate, [12] PyBroP, [13] PPh 3 /Br 2 [14] ), sulfur halides (SO 2 Cl 2 , [7a,15] SOCl 2 , [16] SOBr 2 , [16a] MeSO 2 Cl, [17] ArSO 2 Cl [13,18] ), acyl halides (acetyl chloride, [19] benzoyl halides, [20] oxalyl chloride, [21] chloroformates, [20b,22] triphosgene, [23] Cl 3 CCOCl, [24] F 3 CCOCl [22b,24–25] ), and some other reagents [13,26] . The most commonly used methods incorporate the use of phosphorus oxychloride as both an electrophilic activation agent and a halogen source.…”

Rapid and Effective Reaction of 2-Methylpyridin-N-oxides with Triphosgene via a [3,3]-Sigmatropic Rearrangement: Mechanism and Applications

“…In the same work, a low yield (35%) was obtained from 2-picoline- N -oxide to 2-chloromethylpyridine using phosgene in the presence of TEA . In another work, three 2-chloromethylpyridines were produced in high yields (72–92%) from N -oxides of three α-picolines with diphosgene or triphosgene in the presence of a tertiary amine at very low temperatures −20 or −40 °C . In the two papers, however, there is no mention of the reaction mechanism of α-picoline- N -oxides with phosgene and its substitutes, diphosgene (trichloromethyl chloroformate, TCF) and triphosgene (bis-(trichloromethyl)­carbonate, BTC).…”