Iodine IODOANILINE

Into a 1-litre beaker, provided with a mechanical stirrer, place 36 - 8 g. (36 ml.) of aniline, 50 g. of sodium bicarbonate and 350 ml. of water cool to 12-15° by the addition of a little crushed ice. Stir the mixture, and introduce 85 g. of powdered, resublimed iodine in portions of 5-6 g, at intervals of 2-3 minutes so that all the iodine is added during 30 minutes. Continue stirring for 20-30 minutes, by which time the colour of the free iodine in the solution has practically disappeared and the reaction is complete. Filter the crude p-iodoaniline with suction on a Buchner funnel, drain as completely as possible, and dry it in the air. Save the filtrate for the recovery of the iodine (1). Place the crude product in a 750 ml. round-bottomed flask fitted with a reflux double surface condenser add 325 ml. of light petroleum, b.p. 60-80°, and heat in a water bath maintained at 75-80°. Shake the flask frequently and after about 15 minutes, slowly decant the clear hot solution into a beaker set in a freezing mixture of ice and salt, and stir constantly. The p-iodoaniline crystallises almost immediately in almost colourless needles filter and dry the crystals in the air. Return the filtrate to the flask for use in a second extraction as before (2). The yield of p-iodoaniline, m.p. 62-63°, is 60 g. 

The ICl-CaC03 procedure required a filtration to remove insoluble, inorganic by-products prior to biphasic extraction. In an effort to develop a homogeneous process for the iodination step, a pH control protocol was later implemented in the manufacturing process. The pH-controlled iodination was run in a single phase in a MeOH-water system by simultaneous addition of the aqueous IC1 solution and 1M NaOH. Citric acid was added to increase the buffer capacity to the optimal pH (5-5.5) for robust operation. Under these conditions, the iodoaniline 28 was typically obtained in >99 A% with <1% of diiodoaniline 32. Residual... 

The Merck process group in Rahway has developed two syntheses of rizatriptan (4) utilizing palladium catalyzed indolization reactions (Schemes 19 and 20). Both routes start from the iodoaniline 51, which was prepared by reaction of 47 with iodine monochloride in the presence of CaCOa. " Palladium catalyzed coupling of iodoaniline 51 with bis-triethylsilyl protected butynol in the presence of NaaCOa provided a mixture of indoles 52a and 52b. This mixture was desilylated with aqueous HCl in MeOH to furnish the tryptophol 53 in 75% yield from 51. Protection of the alkyne prevented coupling at the terminal carbon of the alkyne and tnethylsilyl (TES) was found to be optimal because it offered the correct balance between reactivity (rate of coupling) and... 

Iodine, detection of, 1041, 1042, 1043, 1045 recovery of, 647 Iodine monochloride, 974 5-Iodo-2-ammotoluene, 647 p-Iodoaniline, 647 Iodobenzene, 533, 538, 591, 598 Iodobenzene diacetate, 541 Iodobenzene dichloride, 534, 541 o-Iodobenzoic acid, 760... 

In a 3-I. beaker are placed no g. (1.2 moles) of aniline, 150 g. (1.76 moles) of sodium bicarbonate and 1 1. of water, and the mixture is cooled to 12-15° by the addition of a small amount of ice. The beaker is then fitted with ail efficient mechanical stirrer. The blade of a large porcelain spatula should be inserted into the liquid to overcome the rotary motion and thus obtain better mixing. The stirrer is started and 254 g. (1 mole) of powdered iodine is added in 15-20 g. portions at intervals of two to three minutes so that all the iodine is introduced during the course of one-half hour. Stirring is continued for twenty to thirty minutes. By this time the reaction is complete, and the color of the free iodine in the solution has practically disappeared. The crude -iodoaniline, which separates as a dark crystalline mass, is collected on a Biichner funnel, pressed as free from water as possible, and dried in the air. The filtrate may be saved for the recovery of iodine (Note 1). 

The sodium iodide which remains in the aqueous solution may be converted into iodine as follows To the aqueous filtrate from the -iodoaniline are added 100 cc. of concentrated sulfuric acid and 200 g. of sodium dichromate in 200 cc. of water. The iodine is allowed to settle, washed three times with water by decantation, collected on a filter, and allowed to dry on a watch glass. The yield of crude iodine is 167-179 g. 

Iodoaniline has been prepared by the reduction of -nitro-iodobenzene 1 by the hydrolysis of -iodoacetanilide formed by the action of iodine monochloride on acetanilide 2 and by the direct iodination of aniline.3 The method described here is an adaptation of the procedure used by Wheeler/ and by Hann and Berliner 5 for the iodination of the toluidines. 

Cuatrecasas (45). The Dolichos biflorus lectin was a gift from Dr. Marilynn Etzler (46). Ulex europeus and Bandeirea simplicifolia lectins were purified in our laboratory and iodinated with Nal25i (carrier-free) by Sepharose 4B-bound lactoperoxidase (47)and diazotized iodoaniline coupling (48) procedures, respectively. 

Iodophenol was first obtained as a by-product of the action of iodine on salicylic acid in alkaline solution or by heating iodo-salicylic acid.1 It has also been obtained by the action of iodine on phenol in alkaline solution2 or in the presence of mercuric oxide,3 or by the action of iodine monochloride.4 It is best prepared by the diazotization of -aminophenol and replacement of the diazonium group by iodine 5 although it has also been obtained from />-iodoaniline by diazotization and replacement of the diazonium group by hydroxyl.6... 

In the first example, nitration of the benzoate (140) with nitric acid affords the nitro derivative. Hydrogenation converts this to the anthranilate (141). In one of the standard conditions for forming quinazolones, that intermediate is then treated with ammonium formate to yield the heterocycle (142). Reaction of 142 with phosphorus oxychloride leads to the corresponding enol chloride (143). Condensation of 143 with m-iodoaniline (144) leads to displacement of chlorine and consequent formation of the aminoquinazoline (145). Reaction with the trimethylsilyl derivative of acetylene in the presence of tetrakis-triphenylphosphine palladium leads to replacement of iodine by the acetylide. Tributylammonium fluoride then removes the silyl protecting group to afford the kinase inhibitor erlotinib (146). ... 

Acetoxymercuri-o-iodoaniline melts at 149° C. the hydroxide has M.pt. 152° C. the iodide, M.pt. 188° C. With iodine the acetyl derivative gives 2 4-di-iodoacetanilide. ... 

Ionized aniline may exist in a conventional-ion form as well as in isomeric distonic forms, and gas-phase MS experiments performed by Chyall and Kenttamaa134,135 have also been used to form and to study the intrinsic reactivity of these high-energy isomers. Via collision-induced dissociation (CID) of protonated 2-, 3- and 4-iodoanilines in a dual-cell Fourier transform ion cyclotron resonance spectrometer, the 2-, 3- and 4-dehydroanilinium ions were formed as the result of loss of an iodine atom (Scheme 41). Ion/molecule reactions and energy-resolved CID experiments demonstrated that these three ions as well as ionized aniline behave distinctively. The reactivity of three distonic ions... 

The oxidation of p-iodoaniline (68g) in ACN occurs in a similar way, according to equation 6 and producing 4-amino-4 -iododiphenylamine (70g) and iodine (no Agl precipitated after the addition of Ag+ ions). However, iodine is unable to iodinate the parent aniline 68g in ACN109. 

Fluoro-4-iodoaniline was obtained from Aldrich Chemical Company, Inc., and used without further purification. It can also be prepared by iodination of 2-fluoroaniline.2... 

A mother-liquor containing about 1 mole of Nal and about 0.8 mole of NaHC03, from the preparation of p-iodoaniline, is treated with 100 ml of concentrated H2S04 and 200 g of Na2Cr207 in 200 ml of water. The iodine is allowed to settle, washed by decantation with water three times, filtered off, and dried on a watch-glass. 

Iodoaniline 5 03,504 A solution of IC1 (1 mole) is prepared from iodine (127 g) in glacial acetic acid (150 ml) (cf. page 182). When this is dropped, with stirring, into a solution of acetanilide (1 mole) in glacial acetic acid (150 ml) (exothermic reaction ) and the whole is stirred for a further few hours, p-iodoacetanilide is precipitated. After 12 h, the mixture is poured into water (21), and the product is collected and washed with water and dilute sodium hydroxide solution. Recrystallization of this crude material from ethanol gives a 90 % yield of the amide, m.p. 184°, which is hydrolysed by concentrated hydrochloric acid to p-iodo-aniline. 

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