Iodination of pyridines

Electrophilic iodinations of pyridines are less common iodine in oleum produced only a low yield of 3-iodopyridine (57JCS387). 

The iodination of pyridine, quinoline, and isoquinoline via a-metalation using lithium di-fert-butyltetramethylpi-peridinozincate (TMP-zincate) proceeds smoothly at room temperature using iodine as the electrophile. The chemoselective deprotonative zincation generated 2-iodopyridine 70 and 1-iodoisoquinoline 71 in 76% and 93% yield, respectively. Quinoline metalated preferentially at the 8-position to give 61% yield of the 8-iodo derivative 72 and 26% yield of 2-iodoisoquinoline 73 (Equations 25-27) <1999JA3539>. 

The iodination of pyridine, quinoline, and isoquinoline can be achieved via metallation to the nitrogen using lithium di- rZ-butyltetramethylpiperidinozincate (TMP-zincate) at room temperature. Quinoline metallated preferentially at C (8) to give a 61% yield of the 8-iodoquinoline and isoquinoline gave a good yield of 1-iodoisoquinoline (Scheme 48) <1999JA3539>. 

Similar methodology [21] was used in the preparation of novel heterocyclic systems. Iodination of pyridine 66 afforded 67, an intermediate used in the preparation of 68. 

Another important example of a redox titration for inorganic analytes, which is important in industrial labs, is the determination of water in nonaqueous solvents. The titrant for this analysis is known as the Karl Fischer reagent and consists of a mixture of iodine, sulfur dioxide, pyridine, and methanol. The concentration of pyridine is sufficiently large so that b and SO2 are complexed with the pyridine (py) as py b and py SO2. When added to a sample containing water, b is reduced to U, and SO2 is oxidized to SO3. 

The Perkin reaction is of importance for the iadustrial production of coumarin and a number of modifications have been studied to improve it, such as addition of a trace of iodine (46) addition of oxides or salts of metals such as iron, nickel, manganese, or cobalt (47) addition of catalytic amounts of pyridine (48) or piperidine (49) replacement of sodium acetate by potassium carbonate (50,51) or by cesium acetate (52) and use of alkaU metal biacetate... 

DCCI reacts with hydrazone derivatives or with the thiourea 83 to give nitrogen ylides such as 84 and hence by protonation 3-aminotriazolopyridines (88CC506, 93JCS(P1)705). A solution of iodine in pyridine reacts with propional... 

Reaction of the potassium salt of salicylaldehyde with chlo-roacetone affords first the corresponding phenolic ether aldol cyclization of the aldehyde with the ketonic side chain affords the benzofuran (1). Reduction of the carbonyl group by means of the Wolf-Kischner reaction affords 2-ethyl-benzofuran. Friedel-Crafts acylation with anisoyl chloride proceeds on the remaining unsubstituted position on the furan ring (2). The methyl ether is then cleaved by means of pyridine hydrochloride (3). lodina-tion of the phenol is accomplished by means of an alkaline solution of iodine and potassium iodide. There is thus obtained benziodarone (4)... 

Because this diketene acetal is so susceptible to cationic polymerization, acids cannot be used to catalyze its condensation with diols because the competing cationic polymerization of the diketene acetal double bonds leads to a crosslinked product. Linear polymers can, however, be prepared by using iodine in pyridine (11). Polymer structure was verified by 13c nmR spectroscopy as shown in Fig. 

Electrophilic iodine reagents are extensively employed in iodocyclization (see Section 4.2.1). Several salts of pyridine complexes with 1+ such as bis-(pyridinium)iodonium tetrafluoroborate and b/.s-(collidine)iodonium hexafluorophos-... 

Redox titrants (mainly in acetic acid) are bromine, iodine monochloride, chlorine dioxide, iodine (for Karl Fischer reagent based on a methanolic solution of iodine and S02 with pyridine, and the alternatives, methyl-Cellosolve instead of methanol, or sodium acetate instead of pyridine (see pp. 204-205), and other oxidants, mostly compounds of metals of high valency such as potassium permanganate, chromic acid, lead(IV) or mercury(II) acetate or cerium(IV) salts reductants include sodium dithionate, pyrocatechol and oxalic acid, and compounds of metals at low valency such as iron(II) perchlorate, tin(II) chloride, vanadyl acetate, arsenic(IV) or titanium(III) chloride and chromium(II) chloride. 

For unsubstituted PAH, such as benzo[a]pyrene (BP), pyridinium or acetoxy derivatives are formed by direct attack of pyridine or acetate ion, respectively, on the radical cation at C-6, the position of maximum charge density (Scheme 1). This is followed by a second one-electron oxidation of the resulting radical and loss of a proton to yield the 6-substituted derivative. For methyl-substituted PAH in which the maximum charge density of the radical cation adjacent to the methyl group is appreciable, as in 6-methylbenzo[a]-pyrene (6-methylBP) (Scheme 2), loss of a methyl proton yields a benzylic radical. This reactive species is rapidly oxidized by iodine or MnJ to a benzylic carbonium ion with subsequent trapping by pyridine or acetate ion, respectively. 

The rate of iodination of nitroethane in the presence of pyridine according to the equation... 

Measurements921 of the enthalpy of thermal decomposition and of iodination of the complexes fac- [Mo(CO)3L3] (L = MeCN, pyridine) lead to E (Mo-NCMe)... 

Prior to our original report7 on this method, acceptable and general preparative routes to a-iodocycloalkenones had not been described. Treatment of a p-substituted cycloalkenone with trimethylsilyl azide and a mixture of iodine and pyridine sequentially in dichloromethane has now been reported as a method for the preparation of p-substituted-a-iodocycloalkenones.8 The combination of iodine and pyridinium dichromate has also been reported to provide a-iodoenones from enones as well as from ethynyl carbinols.9 10 Some successes have also been achieved with enones and iodine azide (IN3)11 and iodine/ceric ammonium nitrate.12-14 The submitters first variant5 of the present procedure used carbon tetrachloride as a solvent. In this procedure this solvent has been replaced with the more benign diethyl ether. 

A. 2-lodo-2-cyclohexen-1-one. A 500-mL, three-necked, round-bottomed flask equipped with a 1.5-in. Teflon-coated magnetic stirring bar, glass stopper, 50-mL addition funnel, and a reflux condenser is charged with a 1 1 mixture of 75 mL of anhydrous diethyl ether (Note 1) and 75 mL of pyridine. With vigorous stirring, 53 g (0.21 mol) of iodine (Note 2) is added slowly. At the completion of the addition, the dark brown mixture is stirred an additional 10-20 min until complete dissolution is obtained. 

This preparation illustrates an efficient two-step process for the transformation of a cycloalkenone to the corresponding a-substituted derivative. The first step involves the installation of an a-iodo substituent by a process thought to involve nucleophilic addition of pyridine, iodine capture of the resulting enolate, and pyridine-promoted elimination of pyridine.5 The resulting vinyl iodides are superior to other vinyl halides as participants in a variety of transition-metal catalyzed coupling reactions, illustrated here by the Suzuki coupling with an arylboronic acid. Other coupling partners that... 

Bis(pyridinium)iodonium tetrafluoroborate [I(Py)2BF4] reacts readily with alkenes to afford 1,2-disubstituted products arising from addition of iodine and pyridine. Synthetically more important is, however, the reaction of unsaturated systems with I(Py)2BF4 in the presence of nucleophiles, which provides a general method for vicinal iodofunction-alization of alkenes. In this regard, the addition of a stoichiometric amount of tetrafluo-roboric acid to the reaction medium is often required to avoid the competitive formation of products resulting from pyridine acting as a nucleophile. 

The iron-mediated synthesis of 2-oxygenated carbazole alkaloids is limited and provides only a moderate yield (11%) for the oxidative cyclization to 2-methoxy-3-methylcarbazole using iodine in pyridine as the reagent [90]. Ferricenium hexafluorophosphate is the superior reagent for the iron-mediated arylamine cyclization leading to 3-oxygenated carbazoles (Scheme 12). Electrophilic substitution of the arylamines 16 with the complex salt 6a leads to the iron complexes 17. Oxidative cyclization of the complexes 17 with an excess of ferricenium hexafluorophosphate in the presence of sodium carbonate affords... 

The total synthesis of the furo[3,2-a]carbazole alkaloid furostifoline is achieved in a highly convergent manner by successive formation of the car-bazole nucleus and annulation of the furan ring (Scheme 15). Electrophilic substitution of the arylamine 30 using the complex salt 6a provides complex 31. In this case, iodine in pyridine was the superior reagent for the oxidative cyclization to the carbazole 32. Finally, annulation of the furan ring by an Amberlyst 15-catalyzed cyclization affords furostifoline 33 [97]. 

The double iron-mediated arylamine cyclization provides a highly convergent route to indolo[2,3-fc]carbazole (Scheme 16). Double electrophilic substitution of m-phenylenediamine 34 by reaction with the complex salt 6a affords the diiron complex 35, which on oxidative cyclization using iodine in pyridine leads to indolo[2,3-b]carbazole 36 [98].Thus,ithasbeen demonstrated that the bidirectional annulation of two indole rings can be applied to the synthesis of indolocarbazoles. 

To a mixture of 0.372 g (0.012 mol) of red phosphorus and 4.57 g (0.036 mol) of iodine in 30 ml of carbon disulfide stirred for 10 minutes is added 2.12 g (0.01 mol) of benzoin (alone or dissolved in 10ml of benzene) followed by 0.8g (0.01 mol) of pyridine a few minutes later. The dark reaction mixture is allowed to stand for 3.5 hours at room temperature, then poured into aqueous thiosulfate. The organic layer is separated, the layer is extracted with 25 ml of benzene, and the... 

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