Preparation, structure, and oxidative reactivity of (dichloroiodo)pyridines: recyclable hypervalent iodine reagents

New pyridine-based hypervalent iodine reagents, (dichloroiodo)pyridines, were prepared by chlorination of 2-, 3-, or 4-iodopyridines with NaOCl-HCl at room temperature. Structures of 2-(dichloroiodo)pyridine and 2-(dichloroiodo)-3-propoxypyridine were established by X-ray crystallography. The new (dichloroiodo)pyridines can be used as efficient reagents for oxidation of alcohols to carbonyl compounds and also as chlorinating reagents. The reduced form of the reagents such as 2-iodo-3-propoxypyridine, can be recovered from the reaction mixture in good yields by an acid-base liquid-liquid biphasic protocol.

][20][21][22][23] Most of these compounds are pyridine-derived iodonium salts, which can be used as effective electrophilic pyridine transfer reagents toward various organic substrates.The chemistry of pyridine-based hypervalent iodine compounds of general type PyIX 2 remains undeveloped.Previously, our group reported the preparation of pyridine-based pentavalent iodine reagents, 2-iodylpyridines, by oxidation of corresponding 2-iodopyridines using 3,3-dimethyldioxirane.We have demonstrated that 2-iodylpyridines are useful oxidizing reagents towards alcohols or sulfides. 24However, to the best our knowledge, the pyridine based trivalent iodine reagents such as 2-(dichloroiodo)pyridine have not been reported.In the present paper, we report the synthesis, structural characterization, and reactivity of several (dichloroiodo)pyridine derivatives.These compounds can be used as efficient recyclable oxidants towards alcohols or chlorinating reagents towards electron-rich organic substrates.

Results and Discussion
In our initial experiments, we have found that the reaction of 2-iodopyridine 6 with the HCl-NaOCl combination for 2 hours at room temperature yields 2-(dichloroiodo)pyridine 7 in 89% yield (Scheme 2, eq.1).The solid-state structure of 7 was established by single crystal X-ray crystallography (Figure 1).According to the X-ray crystallographic data, compound 7 has a T-shaped geometry of the iodine(III) center (the Cl1-I1-Cl2 bond angle is 177.21(4)o ), and the bond distances between iodine and chlorine atoms are 2.4488(13) Å (I1-Cl1) and 2.5274( 12) Å (I1-Cl2).This molecular arrangement is similar to the previous reported structure of PhICl 2 1. 25 The ICl 2 fragment in 7 is significantly rotated out of the pyridine plane (50.14(11) o ).There are no close intermolecular contacts in the structure of 7 (the closest intermolecular I-Cl contact is 3.627 Å).The analogous reaction of 2-iodo-3-propoxypyridine 8 under similar conditions gave the expected product 9 in 95% yield (Scheme 2, eq.2).A single-crystal X-ray study of 9 revealed that this compound also has T-shaped geometry with the Cl1-I1-Cl2 angle of 170.12(5) o .7][28][29] Similar to 7, the ICl 2 fragment is rotated out of the pyridine plane (85.46 (9)).Two intermolecular I-Cl contacts at about 3.5 Å are present in the X-ray structure of 9 forming a trigonal-bipyramidal motif.
The chlorination of 3-iodopyridine 10 under similar conditions afforded 3-(dichloroiodo)pyridine 11 in 90% yield (Scheme 2, eq.3), and the reaction of 4-iodopyridine 12 produced the expected dichloride 13 in 49% yield (Scheme 2, eq.4).In general, dichloroiodoarene compounds, ArICl 2 , can serve as useful oxidants or efficient chlorinating reagents towards various organic substrates. 11,30We have investigated the oxidation of alcohols and oxidative chlorination of electron-rich organic substrates using (dichloroiodo)pyridines as reagents.The reaction of benzyl alcohol 14a with 2-iodopyridine dichloride 7 in acetonitrile solution at room temperature gave benzaldehyde 15a, isolated from reaction mixture as the 2,4-dinitrophenylhydrazone derivative in good yield (Table 1).As expected, the oxidation of benzyl alcohol 14a using other dichloroiodopyridines also produced benzaldehyde in good yields.In the reactions of para-chloro-14b or para-nitro-benzyl alcohol 14c under similar conditions, the respective products were obtained in low to moderate yields.When the reaction of cycloheptanol 14d was performed using dichloroiodopyridines under these conditions, the expected ketone was obtained in moderate yields.Compared to the reactions of (dichloroiodo)benzene 1 under the same conditions, the new (dichloroiodo)pyridines afforded respective carbonyl compounds in comparable or better yields.
In the reaction of benzyl alcohol 14a with PhICl 2 (1) in the presence of 2-iodopyridine (6) as additive, the yield of benzaldehyde was improved up to 81%.This result implies that the pyridine moiety present in iodopyridines or (dichloroiodo)pyridines is facilitating the oxidation.Previously, Wicha and co-workers reported that the addition of pyridine resulted in increased reactivity of PhICl 2 (1). 31a Reaction conditions: ArICl 2 (0.300 mmol) and alcohol 14 (0.250 mmol) stirred in acetonitrile (2.0 mL) at room temperature for 24 hours.b Isolated yields as 2,4-dinitrophenylhydrazone derivatives of 15. c In the presence of 2-iodopyridine 6 (1.2 equiv).
In the next step, we have investigated the reactivity of (dichloroiodo)pyridines as chlorine atom transfer reagents towards organic substrates.The reaction of dibenzoylmethane 16 with 2-(dichloroiodo)pyridine 7 gave the corresponding α-mono chloride 17 in good yield.As expected, the reactions of dibenzoylmethane 16 with other (dichloroiodo)pyridine reagents also produced product 17 in moderate yield.In the reactions of 1,4-dimethoxybenzene 18 with (dichloroiodo)pyridines, the corresponding product of monochlorination 19 was obtained in moderate yield.3][34] Among the chlorination reactions, the reactions of 4-(dichloroiodo)pyridine 13 gave the lowest yields because of the low solubility of this reagent in methylene chloride.Finally, we have demonstrated that 2-(dichloroiodo)-3-propoxypyridine 9 can be used as a recyclable reagent.The reduced form of reagent 9, 2-iodo-3-propoxypyridine 8, can be easily recovered from the reaction mixture in over 85% yield by a simple acid-base liquid-liquid biphasic protocol.The recovered compound 8 can be converted to 2-(dichloroiodo)-3-propoxypyridine 9 using standard procedure. 24

Conclusions
In summary, we have prepared new (dichloroiodo)pyridines from respective iodopyridines by chlorination with the HCl/NaOCl combination.Structures of 2-(dichloroiodo)pyridine 7 and 2-(dichloroiodo)-3propoxypyridine 9 were established by X-ray crystallography.According to the crystal data, both compounds have the typical for hypervalent iodine T-shape structure.Compound 9 has a pseudocyclic structure with a short intramolecular interaction between oxygen atom and iodine center.The new (dichloroiodo)pyridines can be used as efficient reagents for oxidation of alcohols to carbonyl compounds and also as chlorinating reagents.The reduced form of the reagents, in particular, 2-iodo-3-propoxypyridine, can be recovered from the reaction mixture in good yields by an acid-base liquid-liquid biphasic protocol.

Experimental Section
General.All reactions were performed under dry argon atmosphere with flame-dried glassware.Dichloromethane and acetonitrile were distilled from CaH 2 immediately prior to use.All commercial reagents were ACS reagent grade and used without further purification.Melting points were determined in an open capillary tube with a Mel-temp II melting point apparatus.NMR spectra were recorded on a Varian Inova 500 MHz ( 1 H NMR). Chemical shifts are reported in parts per million (ppm) and referenced relative to the tetramethylsilane.The known compounds, 3-propoxy-2-iodopyridine (8) 24 and dichloroiodobenzene (1) 9 were prepared according to the reported procedures.
General Procedure for preparation of (dichloroiodo)pyridines Aqueous 12M HCl solution (1.5 mL) was added to a mixture of iodoarene (1.4 to 2.0 mmol) with 5.85% aqueous NaOCl (8.0 mL).The reaction was stirred at room temperature for 2 h (reaction completion was controlled by TLC), and the reaction mixture changed from a light yellow solution to a yellow suspension.After completion of the reaction, the resulting yellow precipitate was separated by filtration.The precipitate was washed with hexane and dried in vacuum to afford analytically pure (dichloroiodo)pyridine product.(7).Chlorination of 2-iodopyridine 6 (410 mg, 2.00 mmol) according to the general procedure afforded 490 mg (89%) of product 7, isolated as a yellow solid: mp 79. 5   (9).Chlorination of 2-iodo-3-propoxypyridine 8 (375 mg, 1.43 mmol) according to the general procedure afforded 452 mg (95 %) of product 9, isolated as a yellow solid: mp 89.1-90.5 o C (from methylene chloride); IR (KBr) cm -1  Single crystals of product 9 suitable for X-ray crystallographic analysis were obtained by slow evaporation of MeCN-CH 2 Cl 2 solution.For details on crystal structure of compound 9 see the CIF file in Supporting Information.Selected crystallographic data for 9: Orthorhombic, P2 1 2 1 2 1 , a = 8.0475( 5  (11)  35 : Chlorination of 3-iodopyridine 10 (410 mg, 2.00 mmol) according to the general procedure afforded 498 mg (90%) of product 11, isolated as a yellow solid: mp 130.5-132.0o C (from methylene chloride) (lit, 35
The reaction was stirred at room temperature for 24 h.After completion of the reaction, a standard solution of 1.

Recovery of 2-iodo-3-propoxypyridine 8
After completion of the reaction of benzyl alcohol 14a with reagent 9, 20% H 2 SO 4 (3.0-5.0 mL) was added.The mixture was extracted with dichloromethane.Treatment of the organic layer according to general procedures for oxidation of benzyl alcohol or chlorination afforded product 15a.To the aqueous layer 20% NaOH (5.0-7.0 mL) was added, and then the mixture was extracted with dichloromethane.The organic solution was dried over anhydrous Na 2 SO 4 and concentrated in vacuum to give 2-iodo-3-propoxypyridine 8 (70 mg, 89%).After completion of the reaction of 1,4-dimethoxybenzene 18 with reagent 9, 20% H 2 SO 4 (3.0-5.0 mL) was added.The mixture was extracted with dichloromethane.Treatment of the organic layer according to general procedures for chlorination of 1,4-dimethoxybenzene afforded product 19.To the aqueous layer 20% NaOH (5.0-7.0 mL) was added, and then the mixture was extracted with dichloromethane.The organic solution was dried over anhydrous Na 2 SO 4 and concentrated in vacuum to give 2-iodo-3-propoxypyridine 8 (67 mg, 85%).