Iodine/NaHCO

A simple one-step synthetic method from 35 for the desired product (98) has been created as the third route [30]. Addition of iodine to the solution of 35 in morpholine and an appropriate alcohol as a solvent at room temperature generated 98a-i in excellent yields as shown in Table 4. In this reaction, use of 10-mol eq. of iodine is recommended to achieve high product yields (compare entry 2 with 1). The reagent system is selected among various trials including Br2, Br2/NaOAc, 4-dimethylaminopyridinium tribromide, NIS, iodine/triethylamine, iodine/K2C03, iodine/NaHCOs, iodine/pyridine, iodine/Nal, iodine/NH4Cl, and iodine only in various solvents. 

To a solution of 0.141 g (0.9 mmol) of /V,/V-2-trimethyl-4-pcntcnamidc (3) in 5 mL of DME/H20 (1 1) are added 1.1-2 equiv of iodine at 20 °C. The homogeneous reaction mixture is stirred for 4 d, then diluted with Et20, treated with sodium thiosulfate and extracted with two 10-mL portions of bt20. The extracts are washed with sat. NaHCO, and brine. After drying over MgS04 the ethereal solution is concentrated yield 0.183 g (85%) d.r. (trans/cis) 90 10 (determined by H NMR) bp IOO C/O.3 Torr. 

To a solution of 0.175 g (1.37 mmol) of 3-methyl-5-hexenoic acid (1) in 4 mL ofCH3CN stirred at 0°C are added 1.04 g (4.1 mmol) of iodine. After 2.5 h the mixture is diluted with Et20, washed with sodium thiosulfate and NaHCO, then brine yield 280 mg (81 %) d.r. (cisjtrans) 86 14. 

Method B A mixture of 1.09 g (5.83 mmol) of tcH-butyl-l-methyl-3-butenylcarbonate and 4.7 g (18.2 mmol) of iodine in 100 mL of dry CH3CN is stirred mechanically under nitrogen at —20 CC for 10 h. 50 mL of a solution of 20% sodium thiosulfate, 5% NaHCO, and Et20 are added and the organic layer is dried over Na2SO and evaporated. The carbonates are purified by chromatography (silica gel. hexane/EtOAc 3 2) civ-isomer yield 1.05 g (70%) trans-isomer yield 0.111 g (7.4%). 

I2, NaHCOs, CH3CN, 0°C, >89% yield. " A variation of the method recycles the iodine by reoxidation with TaCl5/H202 (81-100% yield). With this method ketone derivatives are cleaved more rapidly than aldehyde derivatives. ... 

Stir 5 g chloromethyl resin (1.0 mmol Cl/g) in 40 mL CCI4 for 10 min. Add 165 mg iodine and a solution of 8 mL bromine in 17 mL CCI4 and stir the mixture for 20 h at 24°C in the dark. Filter the resin wash with 150 mL each of dioxane, water, 1 M NaHCOs, water, A/A-dimethylformamide (DMF), methanol, and DCM and dry. The resin weight gain should be -65%. The theoretical weight gain for monobromination of all aromatic rings is 71%. 

The hydrolysis of the amyl chlorides with sodium oleate and caustic soda solution to form the corresponding alcohols is the basis of a flourishing industry and is discussed on another page. The ease of removal of halogen increases markedly from chlorine to iodine and with increasing complexity of the compound. Ethylene chlorohydrin, for example, is easily and smoothly hydrolyzed to ethylene glycol by aqueous sodium bicarbonate CH,0HCH,C1 + NaHCO, aq. - CH,OHCH,OH -H CO. + NaCl... 

The nucleophilic displacement of the iodine moiety in 2-iodoben-zoates mediated by triphenyltin hydride and di-n-butyltin dichloride in aqueous solution has been demonstrated (Eq. 6.16). For example, 2-iodobenzoic acid reacts with a toluene solution of Ph3SnH/l,3-(N02)2 CeH4/aq. NaHCOs to give 89% yield of salicylic acid. 

Stereoselective iodolactonization stereoselective epoxidation. lodolactoniza-tion of 7,8- and 8,c-unsaturated acids with iodine in the presence of NaHCOs exhibits only slight stereoselectivity (kinetic control). In the absence of base, equilibration occurs to ive the more stable rrans-isomers. Epoxides are formed in quantitative yield on methanolysis (CH3OH + NazCOs) of the iodolactones. Examples ... 

Scheme22 a [81,82] b 1M vinylmagnesium bromide, THE, -40°C, 30 C then saturated NaHCOs C oxalyl chloride, DMSO, EtsN, - 78 °C, CH2CI2 then saturated NaHCOs, 91% d 3 equiv. (S)-BINAL, THE, - 78 °C, 1 h, 89% e EtsN, CH2CI2, DMAP, AC2O, rt, 2 h, 98% f sat NaHCOs, THE, Et20, iodine, rt, 36h, 90% g silver benzoate, toluene, 12h, 92% h L1A1H4, THE, 0 °C, 30 min, 94% i H2, Pd/C, EtOAc, rt, 6h, then MeOH, Dowex 50W-X8, then added 3 N NH4OH, 89%...

The bicarbonate (NaHCOs) is a strong enough base to remove the proton from the carboxyic add. Iodine attacks the alkene reversibly to give a mixture of diastereoisomers of the iodonium ion. If the T and Me groups are on the same side of the chain, the carboxylate group can attack the iodonium ion from the back and set up a tram iodolactone. The iodolactone is cleaved by methoxide and the oxyanion displaces iodide to give the epoxide. 

Further proof of the intermediacy of the iodohydrins 85 in the formation of the hydroxy-tetrahydrofurans 80 came from two sources. Firstly, treatment with potassium carbonate led to formation of the corresponding epoxides. Secondly, by providing a second alkene function, suitably positioned to trap the iodohydrin hydroxyl by a 6-eto-trig iodocyclization, we have been able to intercept these species and hence define a new approach to substituted pyrans. Thus, treatment of the dienyl hydroxy-ester 90 with iodine and NaHCO, resulted in the formation of pyrans 92 in the ratio of 3.2 1. Presumably, initial iodohydrin formation 91 is followed by a relatively non-stereoselective 6-exo cyclization. Further chemistry of such products has yet to be carried out, especially efforts to distinguish the two iodine atoms and to cyclize to give furopyran systems <01M1001>. 

Several eburnea-ebumea bisindoles have been obtained through coupling of iminium and enamine species which are in equihbrium under the reaction conditions. For instance, treatment of dehydrovincamone (648) with acetic acid gave the dimeric compound 649. The same dimer was formed from the reaction of vincam-one-AT-oxide with acetic anhydride. Extension of the reaction to criocerine (650) and its derivatives resulted in formation of the dimer 651 (395,396). The phenazine derivative 652 was formed in 30% yield from the reaction of (-i-)-ll-aminovinca-mine 653 with iodine in CHCls/NaHCOs (397). 

Iodine/irradiation/sodium hydrogen carbonate I/i i/NaHCO ... 

Na. The cathodes studied were aqueous solutions of bromine and iodine, air saturated NaHCO solution and NaOH solution. 

Use the molecular volume provided with each compound to calculate its density in g/mL (a) NaHCOs, sodium bicarbonate or sodium hydrogen carbonate (also called baking soda), 0.0389 L/mol (b) I2, iodine, 0.05148 L/mol (c) Hg, liquid mercury, 0.01476 L/mol (d) NaCl, common table salt, 0.02699 L/mol. 

To a solution of azide (1 equiv.) in CH2CI2 and NaHCOs (1 equiv.) was added at 0°C followed by the addition of iodine (5 equiv.), the solution was stirred at room temperature for given time. After completion of the reaction, the mixture was quenched with Na2S203 solution and extracted with EtOAc, organic layer was washed with H2O, brine, dried over Na2S04 and concentrated in vacuo. The residue was purified by column chromatography on silica gel (EtOAc hexanes) to afford the corresponding product. 

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