Synthesis of α,ω-Dimercapto Poly(N-isopropylacrylamides) by RAFT Polymerization with a Hydrophilic Difunctional Chain Transfer Agent

Abstract

A new hydrophilic difunctional reversible addition-fragmentation chain transfer (RAFT) agent, diethylene glycol di(2-(1-isobutyl)sulfanylthiocarbonylsulfanyl-2-methylpropionate) (DEGDIM) was synthesized and shown to be effective in imparting living characteristics to the radical polymerization of N-isopropylacrylamide (NIPAM), providing a route to telechelic poly(N-isopropylacrylamides) (PNIPAM) of predictable molecular weights and narrow molecular weight distributions. The thiocarbonylthio end groups were transformed into thiol groups via aminolysis with near quantitative yields, as determined by a thiol-specific quantitative UV absorbance assay. By using a pyrene-substituted initiator, bis(N-(1-pyrenylbutyl))-4,4′-azobis-(4-cyanopentanamide) (BPAC), it was found that the amount of initiator-derived polymer chains in the DEGDIM mediated polymerization of NIPAM was negligible (∼1%) compared to the amount of polymer chains derived from DEGDIM, the difunctional chain transfer agent. These results support the theoretical calculations and confirm the high purity of R,ω-dithiol telechelic hydrosoluble polymers prepared by the RAFT polymerization process.

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] …”

“…It was reported that aminolysis of PNIPAM trithiocarbonate proceeds quantitatively to the thiol when conducted in the presence of a [370] MMA Ph (28) AIBN [173] MMA Ph (28) 393 [173] MMA C 10 H 7 (42) AIBN B [194] 416 Ph (25) ACVA C [164,474] DMAPMAM Ph (25) AIBN [168] NIPAM C 2 H 5 S (185) 394 [368] NIPAM C 2 H 5 S (189) 394 [374] NIPAM C 12 H 25 S (139) AIBN [324] NIPAM S(PDMAM-b-PNIPAM) (398) AIBN [475] DMAM S(PDMAM) (398) AIBN [475] NAM/NAS C 12 H 25 S (115) AIBN [299] St Ph (24) AIBN [133] St C 4 H 9 S (160) AIBN D [473] St Ph (50) 395 [476] St S(PSt) (398) AIBN [475] VAc small amount of a phosphine reducing agent (TCEP). [371,372] Two groups have compared aminolysis with borohydride reduction for PSt dithiobenzoate. [117,205] One study [205] compared (a) sodium borohydride in aqueous THF, (b) sodium borohydride in toluene with phase transfer catalysis, (c) lithium triethylborohydride in THF, and (d) propylamine in THF.…”

“…[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.…”

Modification of RAFT‐polymers via thiol‐ene reactions: A general route to functional polymers and new architectures

“…au) or V. Bulmus (E-mail: vbulmus@unsw.edu.au) been the removal of the RAFT end-group by reduction or aminolysis 5,6,48,52-59 yielding functional polymers 27,60,61 and polymers with thiol end-groups that can be further modified. 54,56,[62][63][64] This aminolysis approach has a potential serious drawback, as the resultant thiol is susceptible to further oxidation to disulfide leading to bimodal polymer populations composed of thiol and disulfide functional polymers. [53][54][55][56]59,60,65,66 To overcome this problem, our group and others have reported an approach employing aminolysis of the RAFT-end groups in the presence of thiol-reactive compounds such as pyridyldisulfide-bearing 40,67,68 or ene-bearing compounds, 54,56,61,64 leading to simultaneous protection/functionalization of the created thiols.…”

Hydrazine as a Nucleophile and Antioxidant for Fast Aminolysis of RAFT Polymers in Air

“…[7] These methods include radical processes, [8,9] thermolysis, [10][11][12] hydride reduction, [13][14][15] hydrolysis, [16] aminolysis [5,[17][18][19][20][21] and so forth, among which the aminolysis route has been more competitively exercised. Indeed, aminolysis of RAFT polymers is very efficient under mild conditions, and more importantly aminolysis produces highly reactive polymer thiols that have been appreciated in the synthesis of telechelic functional polymers, [5,15,17,20,[22][23][24][25][26] star polymers, [27] block copolymers, [21,23,28] polymer networks/ gels, [29,30] polymer bioconjugates, [25] as well as in the decoration of metal surfaces [14,31,32] and in the selective functionalisation of core-shell nanogels. [22,33] Typically, primary amines are used in the aminolysis of RAFT polymers and under such basic conditions thiols are highly susceptible to oxidation by oxygen in air through a base-catalysed radical process.…”