Ethylene Glycol → o-Iodocumene

HRID 2180642Notes

Reaction equation

HRID 2180642 reaction equation
C([O-])([O-])=O.[K+].[K+].C(O)CO.C1(O)C=CC=CC=1.[I:18]C1C=C2C(=CC=1)NC=C2.[CH:28]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[SH:37])([CH3:30])[CH3:29].IC1C=CC=CC=1C>C(O)(C)C.[Cu]I>[CH:28]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[I:18])([CH3:30])[CH3:29].[CH:28]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[SH:37])([CH3:30])[CH3:29]

Participants

10

Reactant 6

HCID 174Ethylene GlycolHCID 996PhenolHCID 51282-IodotolueneHCID 11430Potassium CarbonateHCID 96003Benzenethiol, 2-(1-methylethyl)-HCID 27823135-Iodo-1H-indole

Product 2

HCID 87931o-IodocumeneHCID 96003Benzenethiol, 2-(1-methylethyl)-

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 3776IsopropanolSolvent

Procedure

Thus, a system comprising 5 mol % of CuI, 2 equiv of K2CO3 and 2 equiv of ethylene glycol in isopropanol (without pre-drying and degassing) at 80° C. under argon was applied for the coupling of various functionalized aryl iodides with thiols. Both aromatic and aliphatic NH2 groups, phenol, carboxylic acid, ketone, ester, amide and aldehyde functional groups are tolerated under these reaction conditions. No deleterious effect is observed when heterocyclic substrates, such as 5-iodoindole, are used. This protocol is also applicable to ortho-substituted substrates; for example, the sterically hindered 2-isopropylthiophenol can be coupled with 2-iodotoluene in 88% yield at 80° C. A 91% yield was obtained when the highly sterically hindered 2-isopropyliodobenzene and 2-isopropylthiophenol were coupled at 100° C. The presence of functional groups in the ortho position of the aryl iodide substrates are tolerated including a hydroxymethyl group and a free NH2 group. As can be seen from the results in FIG. 2, a thiophenol with an ortho carboxymethyl group can be coupled in good yield. In addition, alkyl thiols were also found to be effective nucleophiles. Aryl bromides can be used for the arylation of thiols if the aryl bromide is first converted into the corresponding aryl iodide using CuI (10 mol %), a 1,2-diaminoalkane ligand (e.g., 20 mol % of N,N′-dimethylethylenediamine) and sodium iodide (2 equiv) before the addition of the thiol starting material. In summary, we have developed a general and efficient Cu-catalyzed arylation method for both aryl and alkyl thiols under mild conditions that tolerate a wide variety of functional groups.

Workup

  1. customat 80° C.

Sources & evidence

ORD record
ord-5bfc077fb9734d28883a5f7146a6b02c
Source dataset
uspto-grants-2005_05
Patent number
US06888032B2

Reaction notes

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