Iodoform, preparation reactions

Iodoform reaction. To i ml. of the aldehyde solution, add 3 ml. of 10% KI solution and 10 ml. of freshly prepared sodium hypochlorite solution. Yellow crystals of iodoform, CHI3, soon separate. 

In a 1-litre three-necked flask, fitted with a mechanical stirrer, reflux condenser and a thermometer, place 200 g. of iodoform and half of a sodium arsenite solution, prepared from 54-5 g. of A.R. arsenious oxide, 107 g. of A.R. sodium hydroxide and 520 ml. of water. Start the stirrer and heat the flask until the thermometer reads 60-65° maintain the mixture at this temperature during the whole reaction (1). Run in the remainder of the sodium arsenite solution during the course of 15 minutes, and keep the reaction mixture at 60-65° for 1 hour in order to complete the reaction. AUow to cool to about 40-45° (2) and filter with suction from the small amount of solid impurities. Separate the lower layer from the filtrate, dry it with anhydrous calcium chloride, and distil the crude methylene iodide (131 g. this crude product is satisfactory for most purposes) under diminished pressure. Practically all passes over as a light straw-coloured (sometimes brown) liquid at 80°/25 mm. it melts at 6°. Some of the colour may be removed by shaking with silver powder. The small dark residue in the flask solidifies on cooling. 

Methylene iodide [75-11-6], CH2I2, also known as diio dome thane, mol wt 267.87, 94.76% I, mp 6.0°C, and bp 181°C, is a very heavy colorless Hquid. It has a density of 3.325 g/mL at 20°C and a refractive index of 1.7538 at 4°C. It darkens in contact with air, moisture, and light. Its solubiHty in water is 1.42 g/100 g H2O at 20°C it is soluble in alcohol, chloroform, ben2ene, and ether. Methylene iodide is prepared by reaction of sodium arsenite and iodoform with sodium hydroxide reaction of iodine, sodium ethoxide, and hydroiodic acid on iodoform the oxidation of iodoacetic acid with potassium persulfate and by reaction of potassium iodide and methylene chloride (124,125). Diiodoform is used for determining the density and refractive index of minerals. It is also used as a starting material in the manufacture of x-ray contrast media and other synthetic pharmaceuticals (qv). 

At 225—275°C, bromination of the vapor yields bromochloromethanes CCl Br, CCl2Br2, and CClBr. Chloroform reacts with aluminum bromide to form bromoform, CHBr. Chloroform cannot be direcdy fluorinated with elementary flourine fluoroform, CHF, is produced from chloroform by reaction with hydrogen fluoride in the presence of a metallic fluoride catalyst (8). It is also a coproduct of monochlorodifluoromethane from the HF—CHCl reaction over antimony chlorofluoride. Iodine gives a characteristic purple solution in chloroform but does not react even at the boiling point. Iodoform, CHI, may be produced from chloroform by reaction with ethyl iodide in the presence of aluminum chloride however, this is not the route normally used for its preparation. 

Cormier and Dure (1963) found another type of luciferin and called it protein-free luciferin. Protein-free luciferin was found in the vapor condensate of freeze-drying whole animals, and also in the 3 5-56 % ammonium sulfate fraction of the crude extract noted above. The protein-free luciferin behaved like an aromatic or heterocyclic compound and it was strongly adsorbed onto Sephadex and other chromatography media, requiring a considerable amount of solvent to elute it. The luminescence reaction of protein-free luciferin in the presence of luciferase required a 500-times higher concentration of H2O2 compared with the standard luciferin preparation. Both types of the luciferin preparation had a strong odor of iodoform. 

Bromo- and iodocyclopropanes cannot be prepared by the direct halogenation of cyclopropanes. Substituted chloro- and bromocyclopropanes have been synthesized by the photochemical decomposition of a-halodiazomethanes in the presence of olefins iodocyclopropanes have been prepared from the reaction of an olefin, iodoform and potassium f-butoxide followed by the reduction of diiodocyclopropane formed with tri-w-butyl tin hydride. The method described employs a readily available light source and common laboratory equipment, and is relatively safe to carry out. The method is adaptable for the preparation of bromo- and chlorocyclopropanes as well by using bromodiiodomethane or chlorodiiodomethane instead of iodoform. If the olefin used will give two isomeric halocyclopropanes, the isomers are usually separable by chromatography. ... 

The reduction of iodoform by means of sodium arsenite,6 described both by V. Auger and A. Gutmann, gave such successful results that the other methods were disregarded. The reaction is extremely simple and in the course of a few hours several pounds of pure methylene iodide may be prepared. 

Coughlin 1 has. substantially verified the results of Elbs in the case of bromoform. He obtained only small quantities of this body which can be easily prepared electro-lytically from acetone. The formation of iodoform, on the contrary, takes place smoothly. It is obtained technically according to the above-mentioned patent. Elbs and Herz have established the following conditions for this reaction. 

The reaction is the same as that involved in the usual chemical preparation of iodoform, whereby a colorless solution of hypoiodite (obtained by dissolving iodine in a sufficient quantity of potassium-hydroxide solution) is made to react with alcohol. The decomposition potential of potassium iodide, investigated by Dony-Henault,2 show s that the iodine as such does not act on the alcohol, but only after its conversion into hypoiodite. The iodine ions are set free at the same anode potential no matter if alcohol is added or not. The alcohol does not act as a depolarizer towards the iodine ion the electrical iodoform synthesis is a typical secondary process. 

Although the substitution processes afforded by the action of the primarily discharged anion of an inorganic salt upon an organic body are to be included among the simpler reactions, the results obtained so far in this domain have been very scanty, especially in regard to aromatic substances. The above-mentioned investigations of Elbs and Hertz, as well as those of Forster and Mewes on the electrolytic preparation of iodoform,... 

In recent years, exposing the preparation of the reagent from samarium metal and an oxidant to different stimuli has led to significant improvements in reaction time. Concellon utilized the sonication of samarium metal and iodoform at room temperature to give a solution of Sml2 in THF in approximately 5 min (Scheme 2.3).5 This approach was also used by Flowers to synthesise other Sm(II) species.6 It was also reported that using different oxidants, such as 1,2-diiodoethane, diiodomethane and iodine, works just as well with this technique.5... 

Acyl iodides. Aliphatic and aromatic acyl iodides and diacyl iodides can be prepared from the corresponding chlorides by reaction with anhydrous Nal in absolute acetonitrile, and isolated by liquid-liquid extraction with pentane, which is almost immiscible with acetonitrile. The products can be stored under N over copper powder as stabilizer. The same technique can be used to obtain iodoglyox.ilic esters, ROOCCOl, and iodoformic esters, ROCOl. ... 

Vinyl halides represent yet another important class of intermediates in the conversion of ketones to alkenes. The most widely applied conditions for the conversion of ketones into vinyl halides are those developed by Barton et a/. ° for the conversion of 3p-acetoxyandrost-5-ene-17-one into 3P-hydroxyandrosta-5,16-diene (Scheme 44). These conditions of vinyl halide formation and subsequent reduction have been useful in a number of steroid systems for the introduction of a A -carbon-carbon double bond and have been shown to be compatible with such functional groups as alcohols, isolated double bonds and acetals. The scope of vinyl iodide formation from hydrazones has been studied by Pross and Stemhell, and recently the original reaction conditions were improved by using sterically hindered guanidine bases rather than triethylamine. Haloalkenes have also been prepared from the corresponding ketones by treatment with iodoform and chromium chloride or with phosphorous penta-halides. ... 

The corresponding iodine compound is the common substance, iodoform. It possesses both anesthetic and antiseptic properties and is a most important surgical disinfectant in the case of wounds or cuts. It is solid, crystallizing in beautiful yellow crystals. It is practically insoluble in water but is soluble in alcohol and ether. It is prepared by reactions exactly analogous to those used in the case of chloroform. 

A radical protocol was developed using CI4 with base. Cyclohexane could be iodinated, for example, with CI4 in the presence of powdered NaOH. The reaction led to the use of iodoform on solid NaOH as the iodination reagent of choice, a-lodo ethers and ot-iodolactones have been prepared from the parent ether or lactone via treatment with Et4N 4 HF under electrolytic conditions. 

Sodium bypoiodite, NaOI, which is used for the iodoform reaction [750], is prepared in situ from iodine and sodium hydroxide. 

This procedure has been utilized by Nicolaou to prepare the vinyl iodide (482) in the synthesis of lipo-toxins As and Bs (equation 111). The synthesis of vinyl iodides was also utilized by Bestmann in a stereospecific synthesis of (4 ,6 ,llZ)-hexadecatrienal. A Wittig reaction was used to create the ( )-al-kene (484), and the ( )-diene portion was synthesized via vinyl iodide (485) formation and coupling (Scheme 63). This method has been applied to the synthesis of > C-labeled vinyl iodide (488 equation 112). Labeled iodoform (486) was ma and the reaction conditions altered fhrni those employed by Takai and cowmkers in order to use smaller quantities of the valuable iodoform, relative to C1CI2. 

The fact that the Simmons-Smith reaction is regio- and stereoselective enabled the preparation of tritium containing cyclopropane derivatives useful for biological studies. The tritiated diiodomethane was prepared by reduction of iodoform with sodium arsenite in the presence of tritiated water. The carbene generated from tritiodiiodomethane and triisobutylaluminum in chloroform underwent regioselective addition to the unhindered double bond in perillyl alcohol (34). ... 

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