Methylene iodide, reaction

Melhylenecydobutane-l,2-dicar-boxylic anhydride, 43,27 Methylenecydobutanes by addition of allenes to alkenes, 43, 30 Methylenecyclohexane, 40, 66 Methylene iodide, reaction with zinc-copper couple and cyclohexene, 41, 73... 

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. 

The reaction itself works by the action of Na or K from NaOH or KOH which form what is called a catechoxide dianion with the two OHs of the catechol species. This makes the two ripe for an attack by a methylene halide which can be either DCM (methylene chloride, or dichloromethane), DBM (methylene bromide, or di-bromomethane) or DIM (methylene iodide, or diiodomethane). DCM is cheap and works pretty well, but DBM and DIM work better yet are more expensive. 

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). 

A mixture consisting of 0.69 g (10.5 mmoles) of zinc-copper couple, 12 ml of dry ether, and a small crystal of iodine, is stirred with a magnetic stirrer and 2.34 g (0.7 ml, 8.75 mmoles) of methylene iodide is added. The mixture is warmed with an infrared lamp to initiate the reaction which is allowed to proceed for 30 min in a water bath at 35°. A solution of 0.97 g (2.5 mmoles) of cholest-4-en-3/ -ol in 7 ml of dry ether is added over a period of 20 min, and the mixture is stirred for an additional hr at 40°. The reaction mixture is cooled with an ice bath and diluted with a saturated solution of magnesium chloride. The supernatant is decanted from the precipitate, and the precipitate is washed twice with ether. The combined ether extracts are washed with saturated sodium chloride solution and dried over anhydrous sodium sulfate. The solvent is removed under reduced pressure and the residue is chromatographed immediately on 50 g of alumina (activity III). Elution with benzene gives 0.62 g (62%) of crystalline 4/5,5/5-methylene-5 -cholestan-3/5-ol. Recrystallization from acetone gives material of mp 94-95° Hd -10°. 

Estr-5(10)-ene-3a,17 -diol (10 g, 36.2 mmoles) is added over a period of 1 hr to a refluxing mixture consisting of 60 g (0.92 moles) of zinc-copper couple, 350 ml of dry ether and 180 g (54 ml, 0.67 moles) of methylene iodide. After the addition is complete, half of the solvent is removed by distillation and 200 ml dry ether is added. The reaction mixture is then transferred to a sealed stainless steel tube and maintained for 3 hr at 92° before being cooled in an ice bath and poured into 500 ml of saturated aqueous sodium bicarbonate solution. The resultant mixture is extracted with ether and the extracts are dried over anhydrous sodium sulfate and concentrated to yield a solid residue which gives 8.4 g (80%) 5,19-cyclo-5a,10a-androstane-3a,17) -diol mp 161-163° [aJo 40° (CHCI3), on crystallization from acetone. 

The reactions of dichlorocarbene with morpholine and piperidine enamines derived from cyclopentanone and cyclohexanone have been reported to lead to ring expanded and a-chloromethylene ketone products (355,356). Similarly a-chloro-a, -unsaturated aldehydes were obtained from aldehyde derived enamines (357). Synthesis of aminocyclopropanes (353,359) could be realized by the addition of diphenyldiazomethane (360) and the methylene iodide-zinc reagent to enamines (367). 

Ciamician reported the formation of 3-halogenopyridines in low yield from the reaction of pyrryl potassium with chloroform, or bromo-form, in ether. Similar reactions of pyrrole with benzal chloride and methylene iodide gave 3-phenylpyridine and traces of pyridine, respectively. These reactions were later reinvestigated by Alexander... 

More useful for synthetic purposes, however, is the combination of the zinc-copper couple with methylene iodide to generate carbene-zinc iodide complex, which undergoes addition to double bonds exclusively to form cyclopropanes (7). The base-catalyzed generation of halocarbenes from haloforms (2) also provides a general route to 1,1-dihalocyclopropanes via carbene addition, as does the nonbasic generation of dihalocarbenes from phenyl(trihalomethyl)mercury compounds. Details of these reactions are given below. 

The preparation of cyclopropane derivatives has been greatly facilitated by the development of carbene-type intermediates (see Chapter 13) and their ready reaction with olefins. The preparation of phenylcyclopropane from styrene and the methylene iodide-zinc reagent proceeds in only modest yield, however, and the classical preparation of cyclopropane derivatives by the decomposition of pyrazolines (first employed by Buchner in 1890) is therefore presented in the procedure as a convenient alternative. 

Phenylcyclopropane has been prepared by the base catalyzed decomposition of 5-phenylpyrazoline (33 %),2 by the reaction of 1,3-dibromo-l phenylpropane with magnesium (68%),3 and by the reaction of 3-phenylpropyltrimethylammomum iodide with sodium amide in liquid ammonia (80%)4 However, the method frequently used at present is the reaction of styrene with the methylene iodide-zinc reagent (32%)5... 

Cyclohexene, purification of, 41, 74 reaction with zinc-copper couple and methylene iodide, 41, 73 2-CyclohEXENONE, 40,14 Cydohexylamine, reaction with ethyl formate, 41, 14... 

Zinc-copper couple, 41, 72 reaction with methylene iodide and cyclohexene, 41, 73... 

Cyclopropanation with Halomethylzinc Reagents. A very effective means for conversion of alkenes to cyclopropanes by transfer of a CH2 unit involves reaction with methylene iodide and a zinc-copper couple, referred to as the Simmons-Smith reagent.169 The reactive species is iodomethylzinc iodide.170 The transfer of methylene occurs stereospecifically. Free CH2 is not an intermediate. Entries 1 to 3 in Scheme 10.9 are typical examples. 

The earlier examples of [2 + 1] cycloaddition of a carbene (or carbenoid) on the double bond of alkylidenecyelopropanes to yield spiropentane derivatives were observed as undesired side reactions in the synthesis of alkylidenecyelopropanes through the addition of a carbene to a substituted allene [161]. In some cases the spiropentane derivative was obtained as the major product [161a, c] especially when a large excess of the carbene reagent was used. For example, when methyl 3,4-pentadienoate (610) was treated with a ten-fold excess of methylene iodide and zinc-copper couple the two products 611 and 612 were isolated in 1 4.5 ratio (Scheme 86) [161a]. 

Decarboxylativehalogenation (12,417). The Hunsdiecker reaction is not useful for aromatic acids, but decarboxylative halogenation of these acids can be effected in useful yield by radical bromination or iodination of the thiohydroxamic esters, as reported earlier for aliphatic acids.1 Thus when the esters 2 are heated at 100° in the presence of AIBN, carbon dioxide is evolved and the resulting radical is trapped by BrCCl3 to provide bromoarenes (3). Decarboxylative iodination is effected with iodoform or methylene iodide as the iodine donor. 

Formation of the zinc carbenoid is exothermic and potentially explosive. The ice bath should be present in order to control the reaction temperature, and methylene iodide should be added gradually rather than all at once. During the addition of the methylene iodide, or shortly thereafter, the reaction mixture should develop a cloudy, white appearance. 

The addition of iodine appears to promote the subsequent reaction of the zinc-copper couple with methylene iodide. 

B. Norcarane. In a 500-ml. round-bottomed flask fitted with a magnetic stirrer and a reflux condenser protected by a drying tube filled with Drierite are placed 46.8 g. (0.72 g. atom) of zinc-copper couple and 250 ml. of anhydrous ether. A crystal of iodine is added, and the mixture is stirred until the brown color has disappeared (Note 4). A mixture of 53.3 g. (0.65 mole) of cydohexene and 190 g. (0.71 mole) of methylene iodide is added in one portion (Note 5). The reaction mixture is then heated under gentle reflux with stirring. After 30-45 minutes, a mildly exothermic reaction occurs which may require cessation of external heating. After the exothermic reaction has subsided (approximately 30 minutes), the mixture is stirred under reflux for 15 hours. At the end of this time, most of the gray couple has been converted to finely divided copper. The ether solution is decanted (Note 6) from the copper and unreacted couple, which are then washed with two 30-ml. portions of ether. The washes are combined with the bulk of the solution and shaken with two 100-ml. portions of saturated ammonium chloride solution (Note... 

Norcarane has been prepared by the reduction of 7,7-dichlo-ronorcarane with sodium and alcohol,6 and by the light-catalyzed reaction of diazomethane with cyclohexene.6 The reaction of cyclohexene with methylene iodide and zinc-copper couple represents the most convenient preparation of norcarane which is of high purity. 

Methylene iodide, 300 Michael reaction, 912, 913, 914 Michler s ketone, 982 Mixed melting point, 34, 229, 1028 Mixtures of organic compounds, qualitative analysis of, 1090 -1100 preliminary examination, 1093, 1094 ... 

The analogous l,5-dihydro-37/-2,4-benzodithiepin system can be prepared by the reaction of 1,2-benzenedimethanethiol with either methylene iodide in the presence of base or with aldehydes or ketones in the presence of acid. 

---