Facile and Efficient One‐Pot Transformation of RAFT Polymer End Groups via a Mild Aminolysis/Michael Addition Sequence

Abstract

Summary: The trithiocarbonate end groups of polymers prepared by RAFT polymerization are converted into colorless and stable thioethers in a one‐pot process that combines aminolysis of the trithiocarbonate functions and Michael addition of the resulting thiols to α, β‐unsaturated carbonyl derivatives. This post polymerization procedure, which is carried out under mild conditions to near quantitative conversion, is described in the case of a telechelic poly(N‐isopropylacrylamide) sample bearing isobutylsulfanylthiocarbonylsulfanyl end groups. The chemical composition, purity, and molar masses of the modified polymers are assessed by GPC, 1H NMR spectroscopy and UV‐vis spectroscopy, which together demonstrate the efficiency of the method and confirm that the molecular weight and polydispersity of the precursor RAFT polymer are not affected by the treatment.The facile, one pot synthesis combines the reactions of trithiocarbonate aminolysis and Michael addition of a thiol to an α, β‐unsaturated ester to transform the labile, colored thiocarbonylthio moiety into a stable, colorless thioether.imageThe facile, one pot synthesis combines the reactions of trithiocarbonate aminolysis and Michael addition of a thiol to an α, β‐unsaturated ester to transform the labile, colored thiocarbonylthio moiety into a stable, colorless thioether.

Living Radical Polymerization by the RAFT Process - A Second Update

“…C Compounds not used as RAFT agents directly but served as precursors to other RAFT agents. [370] Poly(dimethylsiloxane) macro-RAFT agent DMAM [370] DMAM-b-HEA [370] 188 [371,372] [371][372][373] 189 [374] C [374] 190 [286] NIPAM [286] St [286] (NIPAM-b-St) [286] St-b-NIPAM [286] (Continued) [286] St [286] (NIPAM-b-St) [286] St-b-NIPAM [286] 192 [375] …”

“…[117] Several groups have found that disulfide formation can be prevented if the thiol formed can be allowed to react in situ. [117,130,373,479,480] For example, end-group reduction can…”

“…[117,130,479] This methodology has been applied to the synthesis of three-armed stars by an in-situ thiol-ene reaction with a triacrylate [130] and has been applied to directly make biopolymer conjugates. [479] A recent study shows that dithioester and trithiocarbonate RAFT agents [R-SC(S)Z] undergo a radical-catalyzed reaction with thiols that results in oxidation of the thiol to a disulfide and concomitant reduction of the RAFT agent to R-H. [481] The relative rates of reaction suggested that dithioester RAFT agents [204] PEGA Ph (58) Butylamine Used in thiol-ene [204] NIPAM SCH 2 CH(CH 3 ) 2 (188) Butylamine/TCEP/HEA butylamine/TCEP/BA One-pot thiol-ene [373] NIPAM SCH 2 CH(CH 3 ) 2 (188) Butylamine/TCEP Used in thiol-ene [371,372] NIPAM Ph (25) LiB(C 2 H 5 ) 3 H Used in thiol-ene [151] NIPAM S(CH 2 ) 2 CO 2 H (170) NaBH 4 Used in thiol-ene [355] NIPAM SC 4 H 9 (166) NaOH/MeOH/EDTA Used in thiol-ene [412] NIPAM Ph (24) Octylamine/DMPP/AMA One-pot thiol-ene [132] NIPAM Ph (24) Octylamine/DMPP/PMA One-pot thiol-ene [132] DEAM Ph (24) Hexylamine/DMPP/MA One-pot thiol-ene [130] St Ph (24) Propylamine/PBu 3 /MA NaBH 4 /PBu 3 /MA One-pot thiol-ene [117] St Ph (24) Propylamine NaBH 4 [205] MMA Ph (82) Hexylamine Conditions to favour disulfide formation [196] MMA Ph (22) Propylamine One-pot methanethiosulfonate [480] NVP OC 2 H 5 (228) NaBH 4 Used in peptide/nucleotide conjugation [396] A Monomer unit adjacent to thiocarbonylthio group. B TCEP -tris(2-carboxyethyl) phosphine hydrochloride, EDTA -ethylenediaminetetraacetic acid, TCEP -tris(2-carboxyethyl phosphine), DMPPdimethylphenylphosphine.…”

Tailoring Confinement: Nano-Carrier Synthesis via Z-RAFT Star Polymerization

“…This removal was conducted by aminolysis, as described by Qiu and Winnik [65]. It was expected that the hollow spheres obtained after the aminolysis show approximately the same molecular weight as before, as the polymer material stays unaltered and the RAFT-core is assumed to be negligibly small compared to the polymer material surrounding it.…”

Sequential thiol‐ene/thiol‐ene and thiol‐ene/thiol‐yne reactions as a route to well‐defined mono and bis end‐functionalized poly(N‐isopropylacrylamide)

“…As such, RAFT offers an attractive, and convenient, route to telechelic (co)polymers simply via the use of functional RAFT agents. 47 In addition, the thiocarbonylthio end-groups are easily modified postpolymerization to a variety of species including cleavage to a thiol, typically with a primary or secondary amine, 5,48,49 cleavage to a thiolate, 50,51 thermolysis to an ene, 52,53 or radicalinduced reduction to a saturated species with, for example, Bu 3 SnH. 54 Importantly, the presence of the reactive thiol, or thiolate, at the x chain terminus allows for further modification reactions to be performed via the versatile thiol-ene chemistry.…”