Phenyliodine(III) Dichloride

PhICl2

[932-72-9]  · C6H5Cl2I  · Phenyliodine(III) Dichloride  · (MW 274.91)

(selective chlorinating reagent by either radical or ionic mechanisms; reagent for electrophilic chlorination; oxidizing agent)

Alternate Names: phenyliodo dichloride; phenyliodoso chloride; phenylchloroiodonium chloride; dichloroiodobenzene; iododichlorobenzene; iodobenzene dichloride; iodosobenzene dichloride; IBD.

Physical Data: yellow solid; mp 115-120 °C (dec.) from CHCl3; d 2.2 g cm-3.

Solubility: sol CCl4, CHCl3, CH2Cl2, POCl3, pyridine; sl sol. Et2O, pet. ether, CS2.

Form Supplied in: not commercially available due to lack of stability.

Preparative Methods: by passage of chlorine gas into a solution of iodobenzene in CHCl3 followed by cooling in ice and filtration (87-94%).1 These recipes specify the use of dry CHCl3 although a later report suggests that ethanol-free solvent is suitable.2 An alternative preparation is by oxidation of iodobenzene using 5 equiv. of NaBO3.4H2O and HCl in MeCN (82%).3 Some substituted homologs may be obtained by these protocols. Other methods include treatment of iodosylbenzene (PhIO) with Me3SiCl in CH2Cl24 and generation in situ by adding sulfuryl chloride to a catalytic amount of PhI.5,6a PhICl2 belongs to a useful class of polyvalent iodine reagents, the utility of which in organic synthesis has been reviewed.6 PhICl2 is a precursor to iodosobenzene, PhIO.7

Purification: purity levels can be determined by iodometric titration (typical values: 98-100%).

Handling, Storage, and Precautions: decomposes slowly on standing; corrosive; sensitive to moisture and light; refrigerate and store under nitrogen.

Chlorination of Alkanes.

PhICl2 is widely used as a selective agent for homolytic chlorination of alkanes, alkenes, and alkynes. Radical chain reactions involving PhICl&bdot; as a hydrogen abstracting species or as a chlorine atom donor to multiple bonds were first recognized by Bloomfield in the chlorination of natural rubber.8 A high selectivity in photochemical chlorination of branched chain alkanes in iodobenzene solution was subsequently ascribed to the intermediacy of PhICl&bdot;.9 Using PhICl2 as the chlorinating agent in a photochemically stimulated chlorination of 2,3-dimethylbutane produced the tertiary chloride with <1% of the primary alkyl chloride.10 High yields of tertiary alkyl chlorides are produced in reactions initiated by traces of B(C6H13)3, possibly in the presence of traces of O2.11 Relative reactivities of primary:secondary:tertiary hydrogen atoms in butane and 2,3-dimethylbutane towards PhICl&bdot; are 1:21:368 at 40 °C in CCl412 (vs. 1:3.9:5.1 for Cl&bdot;), although with 1,4-dimethylcyclohexane a tertiary:secondary reactivity of ~10:1 is reported.13 Towards alkanes substituted with electronegative groups where reactivities are determined by polar effects (e.g. BuCl or PrCN), the isomer distribution of monochlorides is very similar upon photochlorination with Cl2 or PhICl2. For example, with PrCl at 40 °C in CCl4 the ratio of 1,1-, 1,2-, and 1,3-dichlorides is 12:58:31 with Cl2 and 18:48:35 with PhICl2.12 However, competitive reactions of substituted alkanes indicate a slight difference in overall reactivity using Cl2 and PhICl2 as the chlorinating agents.12

The possibility exists that mixed chains occur for substrates with a low homolytic reactivity, involving both PhICl&bdot; and Cl&bdot; as hydrogen abstracting species. The selectivity of PhICl&bdot; for tertiary attack has been applied in the chlorination of various cholestanyl derivatives, when the major products are derived from attack at the axial hydrogen atoms at the 5a-, 9a-, 14a-, or 17a-positions.14 In 3a-(trifluoroacetoxy)androsterone the electronegative substituents cause attack to occur nearly exclusively at the 9-position.15 The remote functionalization of steroids at the 9a-, 14a-, or 17a-positions has been achieved by use of templates which direct the attack of a tethered ArICl&bdot; to the appropriate tertiary position. Thus steroid derivatives with a 3a-substituent (1a) yield nearly exclusively chlorine substitutions at C-9 (eq 1), while with (2) attack is directed to C-14.16 The chlorinations are conveniently performed in a relay method by use of a tethered ArI (1b, 2b, 4) with PhICl2 or Sulfuryl Chloride as the source of chlorine.17 Using this technique with substituent (1b) at the 17a-position of 17a-hydroxyprogesterone, a quantitative yield of the 9a-chloride is observed.18 Template (3) at the 3a-position of cholestanol also directs hydrogen abstraction to the C-9 position upon photolysis with PhICl2.19 With the 3a-substituent (1b), tandem radical reactions have also been observed by use of Cl2 in CBr4 (to form 9-bromo-3-cholestanol) or in the presence of thiocyanogen (to form the 9-thiocyanate).20 With the 3a-substituent (4), attack of the tethered ArICl&bdot; is directed (>54%) to the axial hydrogen at C-17.21

Chlorination of Alkenes.

In general, chlorinations of alkenes using PhICl2 follow a radical pathway when the reaction is initiated by heat or light; in such cases the stereochemical outcome is much influenced by steric factors.22 By contrast, ionic mechanisms predominate when no initiation is used or when Trifluoroacetic Acid is added; Wagner-Meerwein shifts can become important in such cases but are not observed in thermal- or light-induced reactions.22 PhICl2 has been found to be the most selective of a number of chlorinating reagents in the selective formation of trans-1,2-dichlorocyclohexane from cyclohexene (eq 2).23

Similarly, both p-dioxene and 1,4-dihydronaphthalene are converted selectively into the corresponding trans-1,2-dichloro derivatives.24 Under radical conditions (i.e. thermally (40-80 °C) or light-induced) norbornene is converted into mixtures of the exo-cis- and trans-dichloro derivatives (eq 3).25 However, ionic mechanisms appear to operate when the same substrate is treated with PhICl2 in the presence of molecular oxygen, leading to the nortricyclyl chloride (5) together with the 2,7-dichloride (6).25 In general, such reactions are much cleaner using PhICl2 than is the case when using other chlorination reagents. The exo-cis-dichloro acid (7) is the major product when the corresponding endo-norbornenyl acid is treated with PhICl2.26

The selectivity of PhICl2 is further emphasized by its ability to chlorinate a variety of terpenoid alkenes efficiently and without rearrangement.27 Under strictly anhydrous conditions, PhICl2 in dry CHCl3 converts cholesterol into the 5a,6a-dichloro derivative (eq 4), probably via a cyclic transition state, whereas molecular chlorine gives the 5a,6b-epimer via an ionic mechanism.28 Under radical conditions, PhICl2 converts acenaphthylene into the trans-dichloride whereas molecular chlorine leads to the corresponding cis-isomer; both transformations are not especially efficient however.29 Chlorinations of 1,3-dienes are, in general, not especially useful except in special cases30 and rearrangements can occur in chlorinations of alkenyl cyclopropanes by PhICl2 (eq 5).31

Chlorinations of Alkynes.

Disubstituted alkynes are chlorinated by PhICl2 under radical conditions (CHCl3, AIBN, reflux) to give mainly (E)-dichloroalkenes (eq 6).32 Depending upon the conditions used, molecular chlorine gives either predominantly the corresponding (Z)-isomers or complex mixtures.

Electrophilic Substitution.

The chlorination of aromatic systems by PhICl2 is often very efficient. For example, salicylic acid is converted into the 5-chloro derivative in 89% yield (eq 7)33 and high yields of chlorinated pyrroles34 and 5-chlorouracils35 can be similarly obtained.

Other Chlorinations.

a-Chloro ketones can be prepared from the parent ketones or 1,3-diones using PhICl2 under either ionic or radical conditions, although the latter photo-induced method is often more selective.5 The reagent when prepared in situ from iodobenzene (cat.) and sulfuryl chloride is suitable for these conversions, for which a full recipe is given in a review.6a Perchloro-a,a-dichloro ketones have been prepared by treatment of the corresponding perchloro-a-diazo ketones with PhICl2.36 Similarly, a-chloro ethers can be obtained from the parent compounds using PhICl2; when chlorine is used, a,a-dichloro ethers are generally obtained.37 Stabilized phosphorylides such as Ph3PCHCO2Me are converted into the corresponding a-chloro derivatives upon exposure to PhICl2.38 In the case of an acylphosphorane, the intermediate a-chlorophosphonium salt can be hydrolyzed by base to give the corresponding a-chloro ketone. Perhaps surprisingly, a-alkoxyphosphoranes from the SCOOPY reaction sequence react with PhICl2 to provide reasonable yields of (Z)-vinyl chlorides (eq 8), whereas reaction with N-Chlorosuccinimide gives the corresponding (E)-isomers.39

In similar fashion to the foregoing, aryl aldoximes also undergo a-chlorination by PhICl2; these intermediates are deprotonated in situ to give the corresponding nitrile oxides which are also trapped in situ, leading finally to 60-75% yields of the [1,3]-dipolar adducts (eq 9).40 By contrast, similar treatment of aryl ketoximes simply results in hydrolysis back to the parent alkaryl ketone.41 The reaction fails with oximes derived from dialkyl ketones.

Remote Functionalization of Steroids.

PhICl2 is a key reagent in a method for the remote functionalization of steroids developed by Breslow and his colleagues. The reaction is a radical relay mechanism in which an aryliodine dichloride is generated in situ from a suitable iodobenzene derivative (e.g. eq 10).42 A chlorine atom is then transferred to an adjacent tertiary position (the 14-position in the example shown); subsequent elimination of HCl and esterification completes the sequence leading to a D14-unsaturated derivative. By varying the length and position of the side chain carrying the iodoaryl function, selective chlorination at both C-9 and C-17 positions can be achieved.42,43 More recent developments feature a somewhat different mechanism wherein an S-chloro species, derived from a similarly tethered heteroaromatic ligand and PhICl2, is a key chain component.44 Prior to these developments, PhICl2 alone, under photolytic conditions,45-47 was found to show considerable selectivity for C-9 in suitably designed steroids.48

Oxidations of Sulfides and Selenides.

Sulfides49 and diaryl selenides6a,50 are rapidly oxidized to the corresponding sulfoxides and selenoxides by PhICl2, which is a more powerful oxidant than metaperiodate in such reactions. Despite this, the reactions can be controlled such that sulfones are not formed. Sulfoxides can also be converted into a-chloro derivatives using PhICl2;51 it is therefore not surprising that sulfides can be directly transformed into a-chloro sulfoxides (sulfone formation may compete) by lengthier exposure to excess reagent (eq 11),52 which can also be used to obtain perfluorosulfuryl chlorides from the corresponding sulfinic acids.53

Oxidation of Alcohols.

PhICl2 in the presence of a weak base such as pyridine can be used to oxidize secondary alcohols to ketones (eq 12).54 The method is not suitable for primary alcohols or diols or to unsaturated substrates due to competing chlorination.22-32


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David W. Knight

University of Nottingham, UK

Glen A. Russell

Iowa State University, Ames, IA, USA



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