Alkyl iodides, reaction with sodium

Alkyl iodides. Many primary, secondary, and benzylic alcohols are converted into alkyl iodides by reaction with sodium iodide in the presence of PPSE. The reaction proceeds with inversion in the case of secondary alcohols. Yields of 80-98% are often obtainable, but isomerization or elimination can be important side reactions, particularly in the cases of allylic alcohols, 1,2-diols, and tertiary alcohols. 

Reissert compounds of the type 33 (n = 330,49 and 430) undergo an intramolecular alkylation on treatment with sodium hydride in dimethyl-formamide to give the tricyclic compounds (34). A similar reaction also takes place in the quinoline series.30 When 33 (n = 3) and isopropyl bromide are treated with sodium hydride, cyclization to 34 (n = 3) takes place rather than alkylation with the isopropyl bromide however, treatment of 33(n = 3) and carbon disulfide-methyl iodide with sodium hydride gives 35 rather than cyclization.30 Alkaline peroxide converts the nitrile 34 (n = 3) into an amide, and acid or base hydrolysis gives 4-(l-isoquinolyl)butyric acid.30... 

The (S)-lactone acid 1, obtained from L-glutamic acid by nitrous acid deamination, was converted to the acid chloride, then treated with excess diazomethane followed by hydrogen iodide to yield the keto-lactone 2. Amidation occurred quantitatively to give the partially racemized amide 3, which was purified by repeated recrystallizations. The vicinal diol resulting from reaction with excess methylmagnesium iodide was protected as the acetonide 4. An isomeric mixture of olefins (Z , 26 74) was obtained from the subsequent Wittig reaction. Reduction followed by separation on silver nitrate coated silica gel gave the (Z)-and ( )-alcohols in 20% (6) and 61% (5) yield, respectively. Conversion of the (S)-( )-alcohol (5) to the chloride then afforded the thioether (7) on reaction with sodium phenylsulfide. The thio ether anion was formed by treatment with n-butyllithium. Alkylation with the allylic chloride" (8), followed by removal of sulfur, then yielded the diene 9, which was converted in several steps to (/ ) (-t-)-10,11 -epoxy famesol. 

Marvel and co-workers [7] were one of the first groups to study in detail the preparation and polymerization of alkyl thioacrylates. Mikeska [8] earlier prepared thioacrylic esters by the reaction of chloropropionyl chloride and the mercaptan followed by dehydrohalogenation with diethylaniline. Marvel prepared alkyl thioacrylates by the reaction of a,yS-dibromopropionyl chloride with mercaptan followed by the reaction with sodium iodide to eliminate the bromine atoms to give the acrylate ester. 

The insolubility of some salts in organic solvents can be used to drive an equilibrium in the direction required. For example, in the synthesis of this alkyl iodide from the alkyl bromide by reaction with sodium iodide, acetone is used as the solvent. Why Well, sodium iodide is rather more soluble in acetone than is sodium bromide so as sodium bromide is removed from the equilibrium mixture, more of the starting materials have to convert to the products to restore the equilibrium constant. You will meet more on this reaction in Chapter 15. 

Several approaches have been used to prepare transition-metal-thiolate complexes. The most common synthetic route involves the metathesis reaction of a metal halide with an alkali metal thiolate salt. For instance, [(DPPE)Pd(Ar)(S-t-Bu)] was obtained by treatment of the (DPPE) palladium aryl iodide complex with sodium fprf-butyl thiolate (Equaticm 4.106). Additionally, these compoimds have been formed by proton exchange reactions of thiols with M-C (Equation 4.107), ° M-W and M-O, bonds (Equation 4.108). Finally, the oxidative addition of RSH, or alkyl and aryl disulfides - is a useful way... 

Qualitative tests for alkyl halides are useful in deciding whether the compound in question is a primary, secondary, or tertiary halide. In general, it is quite difficult to prepare solid derivatives of alkyl halides, so this discussion is limited to two qualitative tests (a) reaction with alcoholic silver nitrate solution, and (b) reaction with sodium iodide in acetone. 

Primary alkyl chlorides and bromides can be distinguished from aryl and alkenyl halides by reaction with sodium iodide in acetone (Finkelstein reaction) ... 

The products of the reaction of radical anions, for example sodium naphthalene, with bromides and chlorides are the hydrocarbon, the olefin and alkylated dihydronaphthalene. Reaction with iodides gives hydrocarbon dimer in addition.The mechanism as shown is a result of numerous product and kinetic studies (2 4, 5). Two steps that merit further investigation are the... 

Iodides can be made smoothly from tosylates or bromides by reaction with sodium iodide in acetone.There are also several procedures based on phosphorus reagents which are mechanistically related to those discussed for bromides and chloride. One procedure involves preparation of a cyclic phosphite ester from the alcohol and c -phenylenephosphorochloridite. Treatment of the cyclic phosphite with iodine then generates the alkyl iodide.An alkoxyphosphonium intermediate is involved. 

Iodide ion (I ) Alkyl chlorides and bromides are converted to alkyl iodides by treatment with sodium iodide in acetone Nal is soluble in acetone but NaCI and NaBr are insoluble and crystallize from the reaction mixture making the reac tion irreversible... 

Methyldihydrostrychnidinium-A acetate is produced in much small amount in the hydrogenation ( internal alkylation) reaction and w isolated as the iodide, m.p. 345-350°, and converted to the chloric which on treatment with sodium methoxide gave methoxymethyltetr hydrostrychnidine (c in the above list) with some des-base-D, and < thermal decomposition yielded dihydrostrychnidine-A. These and oth reactions of des-base-D are regarded as best accounted for by formu (XVIII). ... 

The required xanthates 1 can be prepared from alcohols 5 by reaction with carbon disulfide in the presence of sodium hydroxide and subsequent alkylation of the intermediate sodium xanthate 6. Often methyl iodide is used as the alkylating agent ... 

An imidazole derivative which is also a hypotensive agent by virtue of adrenergic a-2-receptor blockade is imiloxan (75). Its synthe.sis begins by conversion of 2-cyanomethyl-1,4-benzodioxane (72) to its iminosMhylether with anhydrous HC in clhanol (73). Reaction of the latter with aminoacetaldehyde diethylacetal and subsequent acid treatment produces the imidazole ring (74). Alkylation of 74 with ethyl iodide mediated by sodium hydride completes the synthesis [251. 

Somewhat similar observations have been made in the reaction of alkyl halides with sodium mirrors (the Wurtz reaction) in which alkyl coupling occurs. Thus, ethane formed on treatment of methyl iodide with sodium in a field of 20 G shows n.m.r. emission (Garst and Cox, 1970). The phase is consistent with polarization via T j-S mixing,... 

The reaction of alkyl halides with metal nitrites is one of the most important methods for the preparation of nitroalkanes. As a metal nitrite, silver nitrite (Victor-Meyer reaction), potassium nitrite, or sodium nitrite (Kornblum reaction) have been frequently used. The products are usually a mixture of nitroalkanes and alkyl nitrites, which are readily separated by distillation (Eq. 2.47). The synthesis of nitro compounds by this process is well documented in the reviews, and some typical cases are listed in Table 2.3.92a Primary and secondary alkyl iodides and bromides as well as sulfonate esters give the corresponding nitro compounds in 50-70% yields on treatment with NaN02 in DMF or DMSO. Some of them are described precisely in vol 4 of Organic Synthesis. For example, 1,4-dinitrobutane is prepared in 41 -46% yield by the reaction of 1,4-diiodobutane with silver nitrite in diethyl ether.92b 1-Nitrooctane is prepared by the reaction with silver nitrite in 75-80% yield. The reaction of silver nitrite with secondary halides gives yields of nitroalkanes of about 15%, whereas with tertiary halides the yields are 0-5%.92c Ethyl a-nitrobutyrate is prepared by the reaction of ethyl a-bromobutyrate in 68-75% yield with sodium nitrite in DMF.92d Sodium nitrite is considerably more soluble in DMSO than in DMF as a consequence, with DMSO, much more concentrated solutions can be employed and this makes shorter reaction times possible.926... 

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