Preparation of alkyl chlorides, acid chlorides, and amides using polymer-supported phosphines and carbon tetrachloride: mechanism of these reactions

Abstract

Alcohols and thiols were converted into alkyl chlorides, carboxylic acids were converted into acid chlorides, and mixtures of carboxylic acids and amines were converted into amides by reaction with carbon tetrachloride and 1% cross-linked polystyrenes containing phosphine residues. Some of these conversions were also effected by using a linear polymer containing phosphine residues. The reactions proceed in high yield, and isolation of the products is facilitated by the ready removal of all the polymer-supported species. The mechanism of the reactions between triphenylphosphine, carbon tetrachloride, and alcohols is complex, but the polymer-supported reactions appear to follow analogous pathways to the low molecular weight reactions as judged by the yields of chloroform and the number of equivalents of phosphine consumed per mole of alkyl chloride produced. The mechanism requires polymer-supported groups reacting together. The slow step in the reactions appears to be the generation of the chlorinating species. The polymer-supported reactions are faster than those using triphenylphosphine or 4-(diphenylphosphinyl)isopropylbenzene. It is suggested that this is due to a microenvironmental effect.

Simple Synthesis of Amides and Weinreb Amides Using PPh3 or Polymer‐Supported PPh3 and Iodine

“…For this polymer-supported PPh 3 (Pol–PPh 3 ) offered a simple solution. As indicated earlier, Pol–PPh 3 has been used for amidation, [16,17] and PPh 3 /CBr 4 has been used in Weinreb amide synthesis. [40] However to our knowledge, Pol–PPh 3 has not been used in combination with the cheaper I 2 .…”

“…In the area of amide bond formation, the combination of PPh 3 with halogen sources such as NCS, [10] NBS, [11] Br 2 , [12] BrCCl 3 , [13] CCl 4 , [13,14] CBr 4 [14] and trichloroisocyanuric acid [15] have all been explored. In addition, polymer-supported PPh 3 (Pol–Ph 3 P) has been utilized for amidation in combination with CCl 4 [16] and Cl 3 CCN [17] .…”

Triphenylbutanamines: Kinesin Spindle Protein Inhibitors with in Vivo Antitumor Activity

“…120–122 °C). 39 1 H NMR (400 MHz, DMSO- d 6 ) δ = 1.07–1.11 (m, 2H, CH 2 ), 2.54–2.58 (m, 2H, CH 2 ), 3.37–3.39 (m, 2H, CH 2 ), 4.46 (t, 1H, OH), 7.22–7.28 (m, 15H, Ph). 13 C NMR (100 MHz, DMSO- d 6 ) δ = 29.0, 36.0, 55.9, 60.9, 125.6, 127.8, 128.7, 147.2.…”

The application of a monolithic triphenylphosphine reagent for conducting Appel reactions in flow microreactors

“…This pathway, therefore, can use up to four equivalents of triphenylphosphine to give up to three brominated products. The rate determining step for both pathways has been proposed to be the formation of an active halogenating species 3 or 10 [40]. The increase in the rate of reaction with regards to the Appel reaction, with solid-supported triphenylphosphine compared to the solution-phase counterpart, is proposed to be a result of neighbouring-group participation assisting in the formation of the active species 9 and 10 in pathway B [39,41–42].…”

“…The increase in the rate of reaction with regards to the Appel reaction, with solid-supported triphenylphosphine compared to the solution-phase counterpart, is proposed to be a result of neighbouring-group participation assisting in the formation of the active species 9 and 10 in pathway B [39,41–42]. Analysis by gas chromatography of chloride Appel reactions indicated that the relative proportion of chloroform was a lot lower than would be expected if both pathways were followed equally in both the solution or solid-phase reactions (5% with solution-based triphenylphosphine and 18–29% with solid-supported triphenylphosphine), indicating that path B is the major pathway in either case [40,43]. …”