Iodides nucleophilic reactions

Nucleophilic Reactions. Useful nucleophilic substitutions of halothiophenes are readily achieved in copper-mediated reactions. Of particular note is the ready conversion of 3-bromoderivatives to the corresponding 3-chloroderivatives with copper(I)chloride in hot /V, /V- dim ethyl form am i de (26). High yields of alkoxythiophenes are obtained from bromo- and iodothiophenes on reaction with sodium alkoxide in the appropriate alcohol, and catalyzed by copper(II) oxide, a trace of potassium iodide, and in more recent years a phase-transfer catalyst (27). 

In addition to bromides and iodides, the reaction has been successfully extended to chlorides,163 triflates,164 and nonafluorobutanesulfonates (nonaflates).165 These reaction conditions permit substitution in both electron-poor and electron-rich aryl systems by a variety of nitrogen nucleophiles, including alkyl or aryl amines and heterocycles. These reactions proceed via a catalytic cycle involving Pd(0) and Pd(II) intermediates. 

Iodide is a good nucleophile. It attacks the least substituted carbon of the oxonlum ion formed in step 1 and displaces an alcohol molecule by S 2 mechanism. Thus, in the cleavage of mixed ethers with two different alkyl groups, the alcohol and alkyl Iodide formed, depend on the nature of alkyl groups. When primary or secondary alkyl groups are present. It Is the lower alkyl group that forms kyl Iodide (Sn2 reaction). 

Hydroxypyridone 337 by triethyloxonium fluoborate was transformed to ether 338 that resisted nucleophilic reactions (76IJB400). Such reactions were possible, however, in the case of pyridone 192a through chloro compound 384. Nucleophilic displacement of triflate 28 resulted in the formation of iodide 29a as the major product (94TL393). 

Intramolecular nucleophilic reaction of sp2-geminated organodimetal species gives cycloalkyl metal derivative, which can be converted into the corresponding alkenyl iodide. The iodide can be used for further transition-metal-catalyzed cross-coupling reaction (equations 61 and 62)86. 

Interestingly, treating (>/4-cyclooctatetraene)Fe(CO)3 with acetyl chloride under Friedel-Crafts reaction conditions yielded unexpectedly222-223 the (>/2,>/3-8-e.x0-acetyl bicy-clo[3.2.1]octadienylium)Fe(CO)3 cation complex, presumably by rearrangement of the intermediate bicyclo[5.1.0]octadienylium isomer (Scheme 8). The structure of the rearranged cation was confirmed from the X-ray crystal structure and from the typical 1,3-cr.ji-allylic products obtained upon nucleophilic reaction with LiAlD4 and NaCN. The nucleophilic reaction of the more bulky iodide occurs, however, on the metal. 

Photostimulated, S r k 1 reactions of carbanion nucleophiles in DMSO have been used to advantage in C—C bond formation (Scheme 1).25-27 Thus, good yields of substitution products have been obtained from neopentyl iodide on reaction with enolates of acetophenone and anthrone, but not with the conjugate base of acetone or nitromethane (unless used in conjunction, whereby the former acts as an entrainment agent).25 1,3-Diiodoadamantane forms an intermediate 1-iodo mono substitution product on reaction with potassium enolates of acetophenone and pinacolone and with the anion of nitromethane subsequent fragmentation of the intermediate gives derivatives of 7-methylidenebicyclo[3.3.1]nonene. Reactions of 1,3-dibromo- and 1-bromo-3-chloro-adamantane are less effective.26... 

When steric hindrance in substrates is increased, and when the leaving anion group in substrates is iodide, SET reaction is much induced (Cl < Br < I). This reason comes from the fact that steric hindrance retards the direct nucleophilic reduction of substrates by a hydride species, and the a energy level of C-I bond in substrates is lower than that of C-Br or C-Cl bond. Therefore, metal hydride reduction of alkyl chlorides, bromides, and tosylates generally proceeds mainly via a polar pathway, i.e. SN2. Since LUMO energy level in aromatic halides is lower than that of aliphatic halides, SET reaction in aromatic halides is induced not only in aromatic iodides but also in aromatic bromides. Eq. 9.2 shows reductive cyclization of o-bromophenyl allyl ether (4) via an sp2 carbon-centered radical with LiAlH4. 

Trifluoromethyl is a wonderful group with numerous substituent effect surprises84. Within the context of discussions of positive halogen , it is well-established85 that solution-phase nucleophilic reactions of trifluoromethyl iodide are consistent with the presence of formally positive iodine, e.g. equation 53. ]... 

The -deuterium KIE for the bromide and for the iodide ion reaction are significantly different and indicate that the nucleophiles are part of transition state of the rate-determining step of these reactions and the decomposition of the halides in chloroform occurs by way of an S 2 mechanism within a triple ion and not through carbocation formation. The kinetic study alone could not distinguish between the mechanistic alternatives, since the same kinetic expression would be obtained for all of the mechanisms. 

Radical cations act both as electrophiles and one-electron oxidants toward nucleophiles (Eberson, 1975 Bard et al, 1976 Eberson et al., 1978a,b Evans and Blount, 1978) as shown in (6), and it is therefore important to find out which factors govern the competitition between these reaction modes. Evans and Blount (1978) measured rate constants and products for a number of [9,10-diphenylanthracene)+ /nucleophile reactions and found that iodide, rhodanide, bromide and cyanide undergo oxidation, whereas nucleophiles that are more difficult to oxidize form a C—Nu bond directly. Entry no. 13 of Table 15 shows non-bonded electron transfer to be feasible for these ions, and the reactions of [perylene]+ with iodide, rhodanide and bromide (entry no. 14) presumably can be classified in the same way. The reaction with chloride ion... 

In the presence of sodamide the anionic form of 2-amino-l-ethylbenzimidazole is substituted by alkyl halides on both the annular and exocyclic nitrogens. With butyl and isopropyl iodides the proportion of dialkylated product is increased. The synthetic utility of such nucleophilic reactions of 2-aminobenzimidazole is exemplified by reactions with ethyl cyanoacetate, acetoacetic ester and ethyl benzoylacetate, when subsequent cyclization of the initial products also gives pyrimidobenzimidazole derivatives (Scheme 117). 

Since monofluorophosphate was detected in solution, it is probable that the reaction is a bimolecular nucleophilic substitution. The inference that the hydrolysis is mechanistically similar might be drawn. The iodide ion reaction has also been examined" and the alternative rate equations (4), (5) proposed. 

Correlation of nucleophilic rate data for phenyldimethylsulfonium ions with common nucleophiles, with pXj values shows that the slopes of the lines, correlate qualitatively with the Edwards hardness parameter for the nucleophile and not with the Swain-Scott n parameter. " " d5,d5-2,4,6-Trimethyl-l,3,5-triammocyclohexane is weakly basic in aqueous solution, because of steric inhibition to solvation of the conjugate acid. " The three NH2 groups are axial and the steric effect also results in reduced reactivity as a nucleophile in Sn2 reactions. Highly stereoselective syntheses of P-C-, N-, and O-glycosides have been carried out by addition of anionic nucleophiles to glycosyl iodides. " 5n2 reactions are involved, but some substrates are susceptible to E2 elimination when treated with highly basic anions. 

The thiolates, though less sensitive to basicity, are more reactive than oxygen anions over the total accessible range of basicity, but intersect the amine line at ca. pA 12. Other reactive nucleophiles which do not fall in the amine, thiolate, or oxygen anion categories are fluoride, thiosulfate, nitrite, azide, and sulfite. Halides other than fluoride, and also thiocyanate, nitrate, sulfate, and thiourea have no reactivity towards p-nitrophenyl acetate (Jencks and Carriuolo, 1960a). The total lack of reactivity of thiocyanate, iodide, bromide, and thiourea, all very polarizable nucleophiles which are reactive to sp carbon, rules out any possibility that polarizability is at all important in nucleophilic reactions at the carbonyl carbon. In general, the order of nucleophilic reactivity to p-nitrophenyl acetate correlates well with nucleophilic reactivity to other carboxylic acid derivatives (see later). Nitrite, however, shows... 

Arylcyclopropanes are obtained from coupling using cyclopropylzinc halides. Carbonylative coupttng. Symmetrical ketones are formed on treatment of organozinc reagents with (PhjPl Pd under CO. In the presence of aryl iodides the reaction with RZnI gives RCOAr. Methacrylic acid derivatives are formed by a Pd-catalyzed reaction of allene, carbon monoxide, and nucleophiles. ... 

As one might expect, the nucleophilicity of (4) is less than (3), and this difference in reactivity is reflected in the alkylation reaction. (4) reacts readily with activated bromides (allylic, benzylic) and the reactions are complete within 12 hours activated chlorides did not react With primary alkyl iodides the reaction is slow (12-120 hours depending on the chain length). With secondary halides, such as 2-bromopropane, ethyl-2-bromopropionate, (l-bromoethyl)benzene and 2-iodopropane, no alkylation was observed. 

The tosylate groups of 47 readily undergo double nucleophilic displacement with a variety of nucleophiles. Reaction of 47 with sodium iodide in acetone provides (2 5,35)-1,4-diiodo-2,3-O-isopropylidene-L-threitol (70) [24]. This is converted in two steps to ( S)-4-hydroxy-2-... 

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