Iodo derivative

Fig. 3. Synthesis of fluoxetine (31). 3-ChIoro-I-phenyl-I-propanol reacts with sodium iodide to afford the corresponding iodo derivative, followed by reaction with methylamine, to form 3-(methyl amin o)-1-phenyl-1-propan 0I. To the alkoxide of this product, generated using sodium hydride, 4-fluorobenzotrifluoride is added to yield after work-up the free base of the racemic fluoxetine (31), thence transformed to the hydrochloride (51)...

Alternatively, radiohalogen-labeled compounds may be prepared by way of isotopic labeling from the unlabeled bromo or iodo derivatives by various two-step reaction sequences. Examples include the use of trialkylsilyl synthons as described in References 10—13, and the use of boronic acid synthons as described in References 14 and 15. 

Very little information is available about other halopteridines such as bromo, fluoro and iodo derivatives, indicating that there is little call for their preparation since, for example, 6-bromo- and 6-chloro-l,3-dimethyllumazine react very similarly (82UP21600). 

The 4- and 5-amino-l,2,3-triazoles are diazotizable, e.g. the diazonium salt from 4-aminotriazole-5-carboxamide with potassium iodide gives the 4-iodo derivative, and that from 4-amino-l,5-diphenyltriazole gives 1,5-diphenyltriazole in ethanol (74AHC(16)33). 

Constitution. On oxidation with chromic acid, conhydrine yields Z-piperidyl-2-earboxylic acid. It is converted into Z-coniine either by reduction of the iodo-derivative (iodoconiine), C,HijNI, formed by the action of hydriodic acid and phosphorus at 180° or by hydrogenation of the mixture of coniceines produced, when it is dehydrated by phosphorus pentoxide in toluene. These and other observations indicate that the p- ygen atom must occur as a hydroxyl group, in the w-propyl side-chain in either the a- (XV) or (XVI) position, since the y-position would involve... 

An apparently related reaction involves iodination in pure methanol in the presence of calcium chloride. The main product is the 21,21-d3-iodo derivative, which on reaction with acetate ion gives, surprisingly, the 21-monoacetate ... 

The 2,2 -bis(phenylthiomethyl) dispiroketal (dispoke) derivative is cleaved by oxidation to the sulfone, followed by treatment with LiN(TMS)2. The related bromo and iodo derivatives are cleaved reductively with LDBB (lithium 4,4 -di- -butylbiphenylide) or by elimination with the P4- -butylphosphazene base and acid hydrolysis of the enol ether. The 2,2-diphenyl dispiroketal is cleaved with FeCl3 (CH2CI2, rt, overnight)." The dimethyl dispiroketal is cleaved with TFA, and the allyl derivative is cleaved by ozonolysis followed by elimination. ... 

The reactivity of arylhalides in the acetylenic condensation sharply decreases in the series Ar—I, Ar—Br, Ar—Cl. The rate of reaction of phenylacetylene with iodo derivatives is 800 times higher than that of the reaction with bromo derivatives and is 10 higher than that of the reaction with corresponding chlorides (75JOM253). Taking into account the very low activity of halogenopyrazoles (66AHC347), the catalytic variant of acetylenic condensation mainly involves the most active iodo derivatives. 

The largest group of acetylene derivatives consists of 4-alkynylpyrazoles owing to the accessibility of the starting 4-iodo derivatives. On the other hand, because... 

Chloro-, 7-bromo- and 7-iodo derivatives were prepared from 2-cycloalkyl-8-hydroxy-2,3,4,6,11,11 u-hexahydro-1 //-pyrazino[l, 2-6]isoqui-noline-l,4-diones by treatment with NCS and NBS in DMF at 70°C for 24 h, with ICl in diluted HCl at 90 °C for 16h, respectively (98MIP7). 

Treatment of this with elemental iodine affords the nuclearly substituted iodo derivative (87). Removal of the benzyl ether by reduction leads to iodothiouracil (88). ... 

Methyl a-D-mannopyranoside was treated in succession with p-toluene-sulfonyl chloride, carbonyl chloride, and benzoyl chloride, and, without isolating the intermediates, there was obtained in 37% yield methyl 4-0-l enzoyl-2,3-O-carbony 1-6-0-(p-tolylsulfonyl ) -D-mannoside. The tos-yloxyl group of the latter was replaced by iodine, and hydrogenation of the 6-iodo derivative in the presence of a nickel boride catalyst gave methyl 4-0-benzoyl-2,3-0-carbonyl-6-deoxy- -D-mannoside. Treatment of the latter with hydrogen bromide in acetic acid gave crystalline 4-0-benzoyl-2,3-0-carbonyl-6-deoxy-a-D-mannosyl bromide (8) (16). The... 

O-isopropylidene derivative (57) must exist in pyridine solution in a conformation which favors anhydro-ring formation rather than elimination. Considerable degradation occurred when the 5-iodo derivative (63) was treated with silver fluoride in pyridine (36). The products, which were isolated in small yield, were identified as thymine and l-[2-(5-methylfuryl)]-thymine (65). This same compound (65) was formed in high yield when the 5 -mesylate 64 was treated with potassium tert-hx Xy -ate in dimethyl sulfoxide (16). The formation of 65 from 63 or 64 clearly involves the rearrangement of an intermediate 2, 4 -diene. In a different approach to the problem of introducing terminal unsaturation into pento-furanoid nucleosides, Robins and co-workers (32,37) have employed mild base catalyzed E2 elimination reactions. Thus, treatment of the 5 -tosylate (59) with potassium tert-butylate in tert-butyl alcohol afforded a high yield of the 4 -ene (60) (37). This reaction may proceed via the 2,5 ... 

Attempted selective displacement (96) of the primary tosylate function in 34 with sodium iodide in refluxing 2-butanone led to the 6-deoxy-6-iodo derivative 35 in 32% yield only, while the di-iodo derivative 36 was formed in 45% yield. These results are to be compared with those reported by Owen and Ragg (85) who observed no reaction with either potassium thiolacetate or potassium thiocyanate in the corresponding / -series. 

The D-gluco analog 37 reacted with sodium iodide in refluxing 2-butanone to give the crystalline 6-deoxy-6-iodo derivative 38 in 82% yield (97). Only 11% of the mixed di-iodo derivative 39 was formed in this case, which reflects on the higher order of reactivity at C-4 in 34 compared to 37. 

The reaction is quite susceptible to steric effects since hindered secondary hydroxyl groups were found to be unreactive. The method can therefore be used to selectively replace a primary hydroxyl group by halogen in the presence of more hindered secondary hydroxyl groups in the same molecule. An example (70) is the reaction of 52 with triphenylphosphite methiodide which affords the 6-deoxy-6-iodo derivative 53 (60%) in which the C-2 hydroxyl group remains intact. 

Whereas l,2-0-isopropylidene-5,6-di-0-methyl-D-glucofuranose was found to be unreactive towards triphenylphosphite dibromide, triphenylphosphite methiodide or phosphorus pentachloride, the related methyl 2,5,6-tri-0-methyl-/ -D-glucofuranoside (59), in which the hindrance caused by the ketal group is absent, reacted with triphenylphosphite methiodide to give the 3-deoxy-3-iodo derivative 60 in 31% yield. 

The reaction was found to be adaptable to dithioacetal derivatives also (70). Thus the product from the treatment of 61 with triphenylphos-phite methiodide was the expected 6-deoxy-6-iodo derivative 62 with no noticeable migration of ketal groups. 

In a similar way, 5-O-acetylthymidine was converted into the 3-deoxy-3-iodo derivative 72 in 55% yield. In this case, the replacement of the hydroxyl group by iodine was presumed to have taken place by retention of the configuration at C-3. The first intermediate in the reaction was proposed to be the phosphonate (70) which rapidly collapses to an O-3-cyclonucleoside (71) and the latter is subsequently attacked by iodide ion to give the product 72. It was also observed (106) that treatment of nucleosides containing a cis vicinal diol grouping such as 5-0-acetyluridine with triphenylphosphite methiodide failed to provide iodinated products but gave phosphonate derivatives instead. 

Benzene- 1,2-diacetonitriles e.g. 19, in the presence of hydrogen bromide in acetic acid, or in diethyl ether, cyclize to 4-bromo-l //-3-benzazepin-2-amines, e.g. 20a.41,42 l//-Naphtho[2,3-t/]azepines, e.g. 22a, are prepared in a similar manner from naphthalene-2,3-diacetonitriles, e.g. 21.41 Replacement of hydrogen bromide by hydrogen iodide yields the corresponding 4-iodo derivatives, e.g. 20b and 22b. 

Bromotrithiatriazepine 8 can also be obtained from the carboxylic acid 6 in 52 % yield by a modified Hunsdiecker reaction involving irradiation of a mixture of the acid, bromine, mer-cury(II) oxide and carbon tetrachloride. The iodo derivative is formed when iodine is employed418... 

Both 4,6- and 3,4-dimethoxydibenzofurans were brominated at C-l [84AHC(35)2]. Iodination of 3 follows the same trends as other halogena-tions (65MI1). Dibenzofuran is lithiated at the 4- and thallated at the 2-position, providing access to 2- and 4-iodo derivatives (57IZV1391). 

Iodination of 4 with molecular iodine in the presence of mercuric oxide formed the 3-iodo derivative (52JA4951 66CJC2283). Iodine in tetrahydro-furan oxidatively cyclized /3-(3-benzo[b]thienyl)-a-mercaptoacrylic acids rather than iodinating the thiophene ring [70JCS(C)2431]. 

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