Ethyl 2-iodoacetate

This substance cannot be prepared, like the two preceding, by esterification of iodoacetic acid with ethyl alcohol. It is necessary to start with ethyl chloroacetate or bromoacetate, both of which react with potassium iodide to form the iodo-compound, 

Perkin and Duppa, commencing with ethyl bromoacetate and potassium iodide, prepared ethyl lodoacetate for the first time. 

ethyl chloroacetate are dissolved in 150 ml. alcohol in a flask fitted with a reflux condenser, then 35 gm. potassium iodide 

The ethyl iodoacetate should be stored in a dark place in order to prevent decomposition. 

Physical and Chemical Properties Ethyl iodoacetate is a colourless, dense liquid boiling at ordinary pressure at 179° C. and at a pressure of 16 mm. at 76° to 78° C. Its specific gravity is i-8. 

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The different configurations of the salts obtained by var3dng the sequence of alkylation are well illustrated by the reaction of pseudo-tropine (14) with ethyl iodoacetate to give 15, while the opposite order... 

KSK Ethyl Iodoacetate, Ethanol, and Ethyl Acetate Mixture ... 

Knochel demonstrated the effectiveness of soluble potassium or cesium alkoxides such as KO Bu or CsO Bu as well as KH in iV-methylpyrrolidinone (NMP) for promoting the 5-endo-dig cyclizations of 2-alkynylanilines to 2-substituted indoles in solution or the solid-phase <00AG(E)2488>. Alternatively, Cacchi coupled a palladium-catalyzed cyclization of o-alkynyltrifluoroacetanilides with the addition of benzyl bromide or ethyl iodoacetate to afford 2-substituted-3-benzyl or 3-indolylcarboxylate esters, respectively <00SL394>. Yamamoto reported a new palladium catalyzed indole synthesis in which 2-(l-alkynyl)-Ar-alkylideneanilines 117 give 2-substituted-3-(l-alkenyl)indoles 118 directly from the imine by the in situ coupling of an aldehyde with the alkynylaniline <00JA5662>. 

More recently, Kim and coworkers have developed a novel radical alkylation reaction of organic nitro derivatives 16a-d via bis(silyloxy)enamines 17a-d (Scheme 16). This method enables not only P -alkylation to the nitro gronp, bnt also the conversion of the nitro group (16a-d) into an oxime ether fnnctionahty (18a-d). The irradiation of a solntion of 16a-d with iodomethyl phenyl snlfone (or ethyl iodoacetate) and hexamethylditin in benzene at 300 nm give the oxime ethers 18a-d in good yields. 

Tin-based reagents are not always snitable owing to the toxicity of organotin derivatives and the difficulties often encountered in removing tin residues from the final product. Therefore, the same authors have carried out additional experiments with 17d and several different alkyl halides under tin-free conditions. The treatment of 16d with tert-butyldiphenylsilyl chloride (TBDPSCl) and triethylamine in the presence of silver triflate in CH2CI2 affords the bis(silyloxy)enamine 17d in 92% yield (Scheme 17). When the radical reaction was carried out with ethyl iodoacetate in the presence of 2,2 -azobis(4-methoxy-2,4-dimethylvaleronitrile) (V-70) as the initiator in CH2CI2, the oxime ether 19 was obtained in 83% yield (Scheme 17). 

The iminium ions produced by the C- alkylation of A2-piperideines can have synthetic utility for the formation of additional carbon-carbon bonds. This concept is illustrated (Scheme 12) by the synthesis of vincamone and its epimer from piperideine (120). Treatment of enamine (120) with ethyl iodoacetate gave iminium ion (121) which cyclized to (122) under the reaction conditions. Completion of the synthesis was accomplished by base followed by acid treatment (82TL177). 

In the previous sections, the reactions of nucleophilic alkyl and acyl radicals with electron-deficient aromatics via SOMO-LUMO interaction have been described. At this point, we introduce the reactions of electrophilic alkyl radicals and electron-rich aromatics via SOMO-HOMO interaction, though the study is quite limited. Treatment of ethyl iodoacetate with triethylborane in the presence of electron-rich aromatics (36) such as pyrrole, thiophene, furan, etc. produces the corresponding ethyl arylacetates (37) [50-54]. 

This reaction comprises firstly of SH2 reaction on the iodine atom of ethyl iodoacetate by an ethyl radical, formed from triethylborane and molecular oxygen, to form a more stable Chester radical and ethyl iodide. Electrophilic addition of the a-ester radical to electron-rich aromatics (36) forms an adduct radical, and finally abstraction of a hydrogen atom from the adduct by the ethyl radical or oxidation by molecular oxygen generates ethyl arylacetate (37), as shown in eq. 5.20. Here, a nucleophilic ethyl radical does not react with electron-rich aromatics (36), while only an electrophilic a-ester radical reacts with electron-rich aromatics via SOMO-HOMO interaction. 

To a mixture of pyrrole (10 mmol), ethyl iodoacetate (1 mmol), and DMSO (5 ml) was added Et3B (1 ml, 1 M hexane solution) under aerobic conditions. After 45 min, Et3B (1 ml) was added again. After the reaction, water was added to the mixture, and the organic layer was extracted with ether, and dried over Na2S04. After filtration and removal of the solvent, the residue was chromatographed on silica gel to obtain the product in 47% yield [51]. 

Irradiation of ethyl iodoacetate in the presence of pyrrole (38) and Na2S203 provides ethyl pyrrolylacetate (39) as shown in eq. 5.21. 

Reaction of ethyl iodoacetate with an excess (5 equiv) of pyrrole in the presence of 2-methyloxirane and BusSnSnBus led to the desired substitution product 1011 in 43% yield, in addition to an undetermined quantity of ethyl phenyl-acetate 1012 (Equation 239), indicating reactivity with the benzene solvent under the reaction conditions <1999TL2677>. The less toxic solvent, methyD-butyl ether (MTBE), provided product 1011 in improved (64%) yield. 

Friedel-Crafts acylation. Posner el al. have developed a remarkably efficient route to the methyl ether of the steroid 11-oxoequilenin (5) from 2-methyl-2-cyclopentenone (1). jS-Addition of the organocoppermagnesium reagent 2 to 1 followed by a-alkylation with ethyl iodoacetate proceeds stereospecifically to give the secosteroid 3 in 94% yield. The final step requires an intramolecular Friedel-Crafts acylation, a reaction that has proved troublesome in previous syntheses of steroids via 9,11-secosteroids. And indeed attempts to cyclize the free acid corresponding to 3 with HF proceeded in yields of 10%. However, cyclization of the ketal acid 4 gives stereochemically pure 5 in 75% yield based on recovered secosteroid. The overall yield from 2-bromo-6-methoxynaphthalene is 52%. 

In a thorough study on the homolytic substitution reaction at silicon, Studer and Steen reported a mild method for the formation of cyclic five-membered alkoxysilanes based on tandem intermolecular add-ition/intramolecular homolytic substitution [137], whereby the reaction of homoallylic stannylated silylether 149 with ethyl iodoacetate in the presence of (Me3Sn)2 led to the desired Sni product 150 in high yield as the sole trans diastereoisomer (Scheme 49). While the 1,2 induction proved to be very high, leading in some cases to a unique diastereoisomer, 1,3 stereoselectivities were... 

Ethyl iodoacetate also reacts easily with sodium thiosulphate. The velocity of this reaction has been studied by Slator. ... 

It is particularly as an eye irritant that ethyl iodoacetate functions, and it seems that this is due to iodoacetic acid and not hydriodic acid. 

Diorgano tellurium compounds have been reacted with methyl iodide (Vol. IX, p 1076), ethyl iodide ethyl iodoacetate, cyclohexyl iodide , methyl bromide, allyl bromide , benzyl bromide , bromoacetone , bromomethyl phenyl ketone , a-bromocarboxylic acids , a-bromocarboxylic acid esters , methyl chloride, and benzyl chloride . 

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