Sodium amide iodide

Methylindole has been prepared from the a5-methylphenyl-hydrazone of pyruvic acid, by the action of sodium amide or sodium hydride on indole followed by methyl iodide at elevated temperatures,by treatment of indole with methyl p-toluene-sulfonatc and anhydrous sodium carbonate in boiling xylene, and by the action of inelhyl sulfate on indole previously treated... 

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... 

The straightforward construction of substituted pyrone 4 proceeded as follows (see Scheme 6c). Alkylation of the monoanion of 2,4-pentanedione (8) with methyl iodide furnishes 3-methyl-2,4-pentanedione. Conversion of this substance into the corresponding dianion with sodium amide followed by selective carboxylation of the more basic site provides intermediate 7. Pyrone 4 is obtained after cyclization with l,l -carbonyldiimidazole and methylation of the resulting enol with dimethyl sulfate. 

The Chemicals. Ethyl iodide can be purchased or made as described in the JCS, 117, 1592 (1920). Either way, it must be purified by fractionally distilling, collecting the fraction boiling at 71.9°-72°. Ammonia must be purchased dry and pure or purified and dried according to the method recommended by Johnson, J. Chem. Ed., 6,443 (1929), using an excess of sodium amide. 

Benzyl-6-methylcyclohexanone has been prepared by the hydrogenation of 2-benzylidene-6-methylcyclohexanone over a platinum or nickel catalyst, and by the alkylation of the sodium enolate of 2-formyl-6-methylcyclohexanone with benzyl iodide followed by cleavage of the formyl group with aqueous base. The 2,6-isomer was also obtained as a minor product (about 10% of the monoalkylated product) along with the major product, 2-benzyl-2-methylcyclohexanone by successive treatment of 2-methylcyclohexanone with sodium amide and then with benzyl chloride or benzyl bromide. Reaction of the sodium enolate of 2-formyl-6-methylcyclohexanone with potassium amide in liquid ammonia formed the corresponding dianion which was first treated with 1 equiv. of benzyl chloride and then deformylated with aqueous base to form 2-benzyl-2-methylcyclohexanone.i ... 

Another way to synthesize ibuprofen consists of the chloromethylation of Ao-butylben-zene, giving 4-Ao-butylbenzylchloride (3.2.24). This product is reacted with sodium cyanide, making 4-Ao-butylbenzyl cyanide (3.2.25), which is alkylated in the presence of sodium amide by methyl iodide into 2-(4-iAo-butylbenzyl)propionitrile (3.2.26). Hydrolysis of the resulting product in the presence of a base produces ibuprofen (3.2.23). 

Isopropamide Isopropamide, (3-carbamoyl-3,3-diphenylpropyl)di-tiO-propylmethyl ammonium iodide (14.1.25), is synthesized by alkylating diphenylacetonitrile with di-/io-propylaminoethylchloride in the presence of sodium amide, and the subsequent hydrolysis of the nitrile group of the resulting compound (14.1.23) to an amide group (14.1.24). Alkylation of this compound with methyliodide gives isopropamide (14.1.25) [19-22]. 

Essentially the same procedure may be used for the preparation of 2,3-dimethylbenzyldimethylamine from 2-methyl-benzyltrimethylammonium iodide except that the time of addition of the latter to the sodium amide is increased to 75 minutes. The checkers found it necessary also to use a larger volume of ammonia. Thus, on a 0.3-mole scale, 1 1. of ammonia was employed, and a total of 600 ml. more ammonia was added during the reaction to maintain the volume at 800 1000 nil. 

The benzylation of diphenylacetonitrile with benzyl chloride to form a,o ,j8-triphenylpropionitrile has been previously effected in 83% yield by sodium ethoxide in ethanol,3 in 67% yield by methylmagnesium iodide in ether,4 and in unreported yield by sodium amide in ether.5... 

The difference in acidity of the a-methylene groups in 2-thenyl compared to 3-thenyl derivatives is clearly shown by the reaction of the quaternary ammonium iodides (322) and (323) with sodium amide. While the former yields a cyclopropane, the latter leads to an allyl derivative (Scheme 95) showing that in the case of (323) it is not the a-methylene which is deprotonated (71JOC2236). 

Exercise 18-39 Show a synthesis of 3-ethyl-2-pentanone from ethyl 3-oxobutanoate. What advantage would this route have over alkylation of 2-pentanone with sodium amide and ethyl iodide (Section 17-4A.)... 

To a solution of 6.7 g of sodium amide in 100 ml of anhydrous diethyl ether was added dropwise 26 g of 4-isobutylbenzene cyanide while the mixture was stirred and heated under gentle reflux. After all of the 4-isobutylbenzene cyanide had been added, the mixture was heated under gentle reflux for 15 min, after which 23.4 g of ethyl iodide was slowly added dropwise thereto from the dropping funnel. After completion of the addition of the ethyl iodide, the mixture was heated under gentle reflux for an initial period of 15 min, after which it was diluted with an equal volume of water and shaken. The two layers that formed were separated and the aqueous layer was then extracted with two 50 ml portions of diethyl ether. The ether extracts were combined and then washed with two 80 ml portions of water and dried over anhydrous magnesium sulfate. The dried ether extract was then distilled at a subatmospheric pressure. In this manner, 25 g of a clear transparent uncolored liquid having a boiling point of 118-122°C at a pressure of 1mm of mercury, which consisted of 2-(4-isobutylphenyl)butyronitrile, was collected. This yield was equivalent to 83% of the theoretical. 

Iodostannates(IV), formation of, by tin (IV) iodide, 4 121 Iron, catalysts for preparation of sodium amide, 2 133... 

Thieno[2,3-6]thiopyran (55) gave methylated derivatives upon treatment with sodium amide followed by methyl iodide. Depending upon reaction conditions, either a mixture of products or exclusively one isomer is formed (Scheme 14). When metallation was carried out with butyllithium,... 

Methyl Phenylethynyl Tellurium1 An apparatus suitable for work with liquid ammonia is set up. Sodium amide is prepared in a 1 -l flask by adding 6.0 g (0.26 mol) of sodium to 250 ml of liquid ammonia, than 25 g (0.25 mol) of phenylacetylene are added dropwise. 30 g (0.24 mol) of tellurium powder are added over 20 min in small portions to the well-stirred sodium amide solution. 36 g (0.25 mol) of methyl iodide are added dropwise over 10 min to the tellurolate solution. The ammonia is then evaporated, the residue is extracted with diethyl ether, the extract is washed with water and the organic phase dried with anhydrous magnesium sulfate. The ether is distilled off and the residue fractionally distilleed under vacuum yield 28 g (48%) b.p. 122-12472 torr (0,267 kPa). 

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