SPOTLIGHT 585

SYNLETT Iodine Monochloride Spotlight 345 Compiled by Luana Silva Magalhães da Forezi

Luana da Silva Magalhães Forezi was born in Recreio/MG, Brazil This feature focuses on a re- in 1984. She received her chemistry degree from the Universidade agent chosen by a postgradu- Federal de Juiz de Fora (UFJF), Juiz de Fora/MG, Brazil in 2008. ate, highlighting the uses and She is currently in the final stages of her M.Sc. studies in organic preparation of the reagent in chemistry, at the Universidade Federal Fluminense, under the su- current research pervision of the Professors Maria Cecília Bastos Vieira de Souza and Fernanda da Costa Santos. Her research interests are focused on the synthesis of new compounds, such as ribonucleoside deriva- tives. Instituto de Química, Universidade Federal Fluminense, CEP 24020-141 Niterói, Rio de Janeiro, Brazil E-mail: [email protected]

Introduction by adding an aqueous solution of potassium iodate to po- tassium iodate dissolved in concentrated HCl, in a closed Iodine monochloride is a chemical compound with the vessel to avoid the loss of chlorine.2 Iodine monochloride formula ICl. Because of the difference in the electronega- is a versatile reagent for the synthesis of a large number of tivity of iodine and chlorine, ICl is highly polar and be- organic compounds being employed, for example, as a haves as a source of I+. Iodine monochloride is a low source of electrophilic iodine in the synthesis of certain melting black or brownish-red solid and widely available aromatic iodides.3 It cleaves C–Si bonds4 and can be used (usually in 97–98% purity). It is soluble in alcohol, ether, in the electrophilic addition to the double bond in alkenes 5 CS2, acetic acid, acetone and pyridine and hydrolyzes in leading to chloroiodoalkanes. When iodine monochlo- water to HCl and IOH. ICl explodes on contact with po- ride is reacted with sodium azide in situ, the iodoazide tassium metal, mixes with sodium metal, and it can ex- product is obtained.6 Other examples of synthetic applica- plode if impacted. Its reaction with PCl3 is extremely tions of this reagent also include electrophilic substitu- exothermic.1 Iodine monochloride can be easily prepared tions in Csp2 and electrophilic cyclizations.7–9

Abstracts

(A) Do and Daugulis showed that the iodination of pentachloroben- Cl Cl zene using a combination of iodine chloride and t-BuOLi in DMF Cl Cl I occurs in excellent yield (90%). Fluorine aromatic compounds like ICl 1,3,5-trifluorobenzene can be either mono- or triiodinated in accept- t-BuOLi able yields, depending on the ratio of the halobenzene to the iodine Cl Cl 90% Cl Cl 3 chloride. Cl Cl

F F

ICl (1 equiv) I t-BuOLi F F 58% F F

F F I I ICl (4 equiv)

t-BuOLi This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. F F 39% F F I

(B) Silylthiophene derivatives as 3,4-difluoro-2,5-bis(trimethylsi-

F F F F

lyl)thiophene can be submitted to an electrophilic substitution reac- ICl

CCl , 0 °C

tion with iodine chloride in anhydrous carbon tetrachloride to give 4

TMS TMS 4 I I

3,4-difluoro-2,5-diiodothiophene in 80% yield. S S

SYNLETT 2011, No. 4, pp 0585–0586 xx.xx.2011 Advanced online publication: 08.02.2011 DOI: 10.1055/s-0030-1259532; Art ID: V35310ST © Georg Thieme Verlag Stuttgart · New York

586 SPOTLIGHT

(C) The addition of ICl to (Z)- and (E)-2-butene occurs in an anti- I

H

H

stereospecific manner: the erythro-2-chloro-3-iodobutane can be ICl

erythro

formed by the addition of ICl to (E)-1-butene, while the other isomer CC

CCl

4

H

(threo) is formed by the addition of ICl to (Z)-1-butene.5 H

Cl

(E)-2-buteno

I

H

ICl

threo CC

CCl

4 H H H

Cl

(Z)-2-buteno

O (D) In their research efforts to modify citidine nucleosides, Verhey- O

den and Moffatt showed that the treatment of enol ether nucleoside

NH 1 with iodine azide, generated in situ from iodine chloride and sodi- NH

um azide, afforded the 4′-azido nucleoside derivative 1a.6 N O N O

ICl, NaN I 3 O O

N 3

OH OH HO HO

11a

H

O

(E) Goodman et al. reported the reaction between 2b-carbo(2-fluo- H

O

N

′ N

roethoxy)-3-{3 -[(Z)-2-trimethylstannylethenyl]phenyl}nortropane ICl

O(CH )nF

2

O(CH )nF

(2) and ICl, leading to compound 4 in good yield. Similar results 2 CHCl

′ 3

were obtained in the case of 2b-carbo(2-fluoropropoxy)-3b-{3 - Sn(Me) 3

[(Z)-2-trimethylstannylethenyl]phenyl}nortropane (3).7 I

4 n = 2 (71%) 2 n = 2

5 n = 3 (55%) 3 n = 3

O

(F) A set of 4-iodoisocoumarins were efficiently prepared by elec- O

MeO trophilic cyclization of ortho-(1-alkynyl)benzoates using iodine MeO

O 8 OMe

monochloride in dichlorometane. ICl

CH Cl

2 2

Ar

MeO C

MeO

0 °C to r.t. C

I Ar

(G) Electrophilic cyclization of 2-chalcogene alkynyl anisole using SePh

I

ICl as an electrophile source produced 3-iodo-2-(phenylsela- C C R R

nyl)benzofuran in good yield. Manarim et al. reported that for this ICl

SePh

CH Cl

2

type of reaction the product distributions were strongly dependent 2 O

–20 °C, 1 h

on the nature of the substituents in the aromatic ring of anisole and OMe

on the chalcogen atom directly bonded to the triple bond.9 R = H (93%)

R = Me (93%)

R = OMe (90%) R = F (75%)

References This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. (1) Brisbois, R. G.; Wanke, R. A.; Stubbs, K. A.; Stick, R. V. V.; Ma, H.; Maile, G.; Merrett, J. H.; Pichota, A.; Sarma, K.; Iodine Monochloride, In Encyclopedia of Reagents for Smith, M.; Swallow, S.; Symons, J.; Vesey, D.; Najera, I.; Organic Synthesis; John Wiley & Sons: West Sussex, UK, Cammack, N. Bioorg. Med. Chem. Lett. 2007, 17, 2570. 2004. (7) Stehouwer, J. S.; Jarkas, N.; Zeng, F.; Voll, R. J.; Williams, (2) Beck, M. T.; Ribai, G. J. Phys. Chem. 1986, 90, 2204. L.; Camp, V. M.; Malveaux, E. J.; Votaw, J. R.; Howell, L.; (3) Do, H.; Daugulis, O. Org. Lett. 2009, 11, 421. Owens, M. J.; Goodman, M. M. J. Med. Chem. 2008, 51, (4) Cardone, A.; Martinelli, C.; Pinto, V.; Babudri, F.; Losurdo, 7788. M.; Bruno, G.; Cosma, P.; Naso, F.; Farinola, G. M. (8) Roy, S.; Roy, S.; Neuenswamder, B.; Hill, D.; Larock, R. C. J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 285. J. Comb. Chem. 2009, 11, 1128. (5) Schmida, G.; Gordon, J. Can. J. Chem. 1986, 64, 2171. (9) Manarim, F.; Roehrs, J. A.; Gay, R. M.; Brandão, R.; (6) Smith, D. B.; Martin, J. A.; Klumpp, K.; Baker, S. J.; Menezes, P. H.; Nogueira, C. W.; Zeni, G. J. Org. Chem. Blomgren, P. A.; Devos, R.; Granycome, C.; Heng, J.; 2009, 74, 2153. Hobbs, C. J.; Jiang, W.; Laxton, C.; Pogam, S. L.; Leveque,

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