Kornblum reactions

The present preparation illustrates a general and convenient method for the fnms-iodopropenylation of an alkyl halide.4 The iodopropenyl-ated material is not usually stable but is a useful synthetic intermediate. For example, it forms a stable crystalline triphenylphosphonium salt for use in the Wittig reaction, and under Kornblum reaction conditions (DMS0-NaHC03, 130°, 3 minutes) it gives an (E)-a,/9-unsaturated aldehyde.4 In addition to the phosphonium salt described in Note 15, the following have been prepared (4-p-methoxyphenyl-2-butenyl)-triphenylphosphonium iodide [Phosphonium, [4-(4-methoxyphenyl)-2-butenyl]triphenyl-, iodide], m.p. 123-127° (2-octenyl)triphenyl-phosphonium iodide [Phosphonium, 2-octenyltriphenyl-, iodide], m.p. 98° and (2-octadecenyl)triphenylphosphonium iodide [Phosphonium, 2-octadecenyltriphenyl-, iodide], m.p. 50°. 

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... 

The reaction of tertiary nitro compounds with the sodium salt of nitromethane followed by the Nef reaction provides a good method forthe preparation of quaternary aldehydes (Eq. 7.10).8 Because the nitromethyl group can be transformed into other groups such as CN, C02H, or CH2NH2, the SRN I reaction of tertiary nitro compounds with the anion of nitromethane is a synthetically useful method (Kornblum reaction).10 For example, the nitromethylation of tertiary nitro compounds has been applied for preparing starting materials for cascade polymers (Eq. 7.11).9... 

The key step in the synthesis of the branched sugars presented in Scheme 7.2 is a Kornblum reaction of the nitropyranose. A mixture of anomers is obtained in the reaction of nitrofuranose, but the reaction with nitropyranose proceeds diastereoselectively to give a single product with an equatorially oriented side chain. 

Direct reactions of poly(vinyl alcohol) with aldehydes in the Kornblum reaction result in formations of acetals that also contain residual hydroxyl group and often acetate groups. The acetate groups can be there from incomplete hydrolysis of the parent poly(vinyl acetate) that was used to form the poly(vinyl alcohol). Reactions of poly(vinyl alcohol) with ketones yield similar ketals. At present, no ketals are offered commercially. 

Mamedov VA, Nuretdinov lA, Sibgatullina FG (1989) Reaction of 3-phenyl-3-chloro-2-oxopropionic acid derivatives with oriho-phenylenediamine. Bull Rus Acad Sci Div Chem Sci 38(6) 1292-1294. doi 10.1007/BF00957177 Mamedov VA, Kalinin AA, Gubaidullin AT, Litvinov lA, Levin YA (2002a) The Kornblum reaction of a-substituted 3-benzyl-l,2-dihydro-2-oxoquinoxalines. Synthesis and structure of 3-benzoyl-2-oxo-l,2-dihydroquinoxaline. Chem Heterocycl Compd 38(12) 1504-1510. doi 10.1023/A 1022601829731... 

With alkali cyanides, a reaction via a SN2-mechanism takes place the alkyl halide is attacked by cyanide with the more nucleophilic carbon center rather than the nitrogen center, and the alkylnitrile is formed. In contrast, with silver cyanide the reaction proceeds by a SnI-mechanism, and an isonitrile is formed, since the carbenium intermediate reacts preferentially with the more electronegative center of the cyanide—i.e. the nitrogen (Kornblum s rule, HSAB concept). ... 

From the foregoing it can be seen that the nitro group can be activated for C C bond formation in various ways. Classically the nitro group facilitates the Henry reaction, Michael addition, and Diels-Alder reaction. Kornblum and Russell have introduced a new substitution reaction, which proceeds via a one electron-transfer process (SrnI). The SrnI reactions have recently been recognized as useful tools in organic synthesis. All these reactions can be used for the preparation of alkenes as described in this chapter. 

Another interesting case concerns a homogeneous electron transfer reaction, namely, the initiation step of the classical Kornblum-Russell reaction153155 of 2-nitropropanate ions with 4-nitrobenzyl chloride (Scheme 14). 

There have, from time to time, been suggestions that electron transfer may mediate in processes which are formally ionic substitution reactions. Whilst such mechanisms have been established for a small number of systems (Kornblum, 1975 Bunnett, 1978), in other instances the evidence is less substantial. For example, dialkylaminyl spin adducts may be observed when secondary amines are allowed to react with picryl chloride in the presence of MNP (Bil kis and Shein, 1974). This can be interpreted in terms of Scheme 12, but alternatives involving nucleophilic addition to the trap merit consideration. 

Kornblum et al. (1963) demonstrated that O- vs. C-alkylation (24) of yS-naphthoxide ion (an ambident ion) is markedly solvent dependent. For example, the reaction with benzyl bromide conducted in dimethylformamide gave 97% O-alkylated product, whereas in water 81% C-alkylated product resulted. The difference is attributed to changes in the solvation of ambident anions. The course of the reaction is also influenced by water concentration in... 

This very rich chemistry has been the subject of several comprehensive reviews, including recent ones sp carbon centres, general (Kornblum, 1975, 1982 Russell, 1970, 1987), photochemically induced reactions (Bowman, 1988a), substituted aliphatic nitro-compounds (Bowman, 1988b), alkyl mercurials (Russell, 1989) sp carbon centres, general (Norris, 1983 Rossi and... 

In a series of recent papers, Komblum et at. have systematically investigated various factors of the reaction at saturated carbon, namely, the stereochemistry (Kornblum and Wade, 1987), the effect of light (Wade et ai, 1987), the effect of leaving groups (Kornblum et al., 1988) and the particular reactivity of the p-nitrocumyl system (Kornblum et al, 1987) as well as the conditions under which the cyano-group may replace the nitro-substituent in reactions involving a benzylic carbon (Kornblum and Fifold, 1989). 

Alkoxide or aryloxide anions are also reputed to be inactive in Sr I reactions. There is, however, one example of such a reaction at an sp carbon the nitro-derivative of 4-nitrocumyl reacts with phenoxide and 1-methyl-2-naphthoxide ions yielding the corresponding ethers (Kornblum et al., 1967). A similar reaction has been reported for halobenzenes in t-butyl alcohol upon stimulation by sodium amalgam (Rajan and Sridaran, 1977). This reaction could not, however, be reproduced (Rossi and Pierini, 1980) and other attempts to make phenoxide ions react at sp carbons have been equally unsuccessful (Ciminale et al, 1978 Rossi and Bunnett, 1973 Semmelhack and Bargar, 1980). It has been found, more recently, that phenoxide ions react with a series of aryl halides under electrochemical induction, but that the coupling occurs at the p- or o-phenolic carbon rather than at the phenolic oxygen (Alam et al, 1988 Amatore et al, 1988). This is... 

The first clue to the existence of the SrnI mechanism came from product studies both in aliphatic and aromatic cases. It was noticed that in the reaction of benzyl and substituted benzyl chlorides with the 2-nitropropane anion, oxygen alkylation, yielding the oxime and then the aldehyde, occurs exclusively in the case of benzyl chloride and 3-nitrobenzyl chloride, whereas, with 4-nitrobenzyl chloride, the yield of aldehyde is only 6% and the carbon-alkylated (104) product is obtained in 92% yield (Kornblum, 1975). This was interpreted as the result of a competition between 8, 2 (O-alkylation) and S l (C-alkylation) reactions. In the aromatic case, it was observed that the reaction of 5- and 6-halopseudocumenes with KNHj in liquid ammonia (Kim and Bunnett, 1970) forms the 5- and 6-pseudocumi-dines in a ratio which is the same whether the starting compound is the 5- or 6-isomer in the case of the chloro- and bromo-derivatives, as expected from an aryne mechanism (Scheme 9), whereas much more non-rearranged... 

Stereochemistry has also been used as a diagnostic tool. If an Sr I reaction occurs at an optically active sp carbon centre, racemization should take place. This has indeed been observed in the reaction of 2-(4-nitrophe-nyl)-2-nitrobutanewithbenzenethiolate,benzenesulphinate,2-nitropropanate and also nitrite ions (Kornblum, 1975 Kornblum and Wade, 1987) as well as in the reactions of 2-(4-nitrophenyl)-2-chloroethane with the V,V-diethyl-a-aminopropionitrile and phenlyacetonitrile anions (Cabaret et al., 1985). 

Another example of sonochemical switching is found in the Kornblum-Russell reaction (Scheme 3.9). 4-Nitrobenzyl bromide reacts with 2-lithio-2-nitro-propane via a predominantly polar mechanism to give, as a final product, 4-nitrobenzaldehyde [57]. An alternative SET pathway exists in this reaction leading to the formation of a dinitro compound. Sonication changes the normal course of the reaction and gives... 

Some chemical additives can induce ion-radical formation and direct the reaction along the ion-radical route. The effect was discovered and studied in cases of nucleophilic substitutions of cumene derivatives (Kornblum 1975, 1982). Cumyl radicals are formed at the first step of substitution irrespective of whether a dissociative or homolytic cleavage takes place as a result of electron transfer to the cumene derivatives (Zheng et al. 1999). 

Thus, sodium azide and a,p-dinitrocumene do not react unless subjected to the action of light (48 h control period). In contrast to sodium azide, the lithium salt of 2-nitropropane reacts with a,p-dinitrocumene in the dark for 3 h, giving the product of a-substitution in 87% yield. When a,p-dinitrocumene (1 mol) is treated with sodium azide (2 mol) in the presence of the lithium salt of 2-nitropropane (only 0.1 mol), the initial a,p-dinitrocumene quantitatively converts into p-nitrocumyl azide for 3 h. The product is extremely pure, and the reaction requires no UV irradiation (Kornblum et al. 1970) (Scheme 5.6). 

Typical one-electron donors, for example, sodium naphthalene, also entrained the reaction of p-nitrocumyl chloride with sodium nitrite (Kornblum et al. 1970). 

If the oxidation is slower than the decomposition, oxygen may affect the nature of reaction products. Thus, treating p-nitrocumyl chloride with sodium malonate ester in a flow of pure dry nitrogen yields a product of C-alkylation (route a in Scheme 5.12) the yield is 90%. Oxygen completely inhibits the C-alkylation, and the reaction gives p-nitrocumyl alcohol in the same yield (route b in Scheme 5.12) (Kornblum et al. 1968). 

Besides solvation, a solvent can also participate in entrainment of ion-radical transformations. The reaction between tertiary aliphatic nitro compounds and the sodium derivative of nitromethane, NaCH2N02, is an example (Kornblum and Erickson 1981). To prepare NaCHjNOj, nitromethane is treated with sodium hydride. Then a tertiary aliphatic nitro compound is introduced into the solution formed. Several organic solvents were probed and CHjSOjCHj (DMSO) turned out to be the most effective. Kornblum and Erickson (1981) attributed this result to the formation of small amounts of NaCH2SOCH3 (sodium dimsyl) that was produced from DMSO as a result of its reaction with sodium hydride. Sodium dimsyl acts as a powerful one-electron reducer that induces the following chain anion-radical process ... 

One of the products was the expected C-substituted compound. The other was an unstable species, which decomposed into 4-nitrocumyl alcohol during workup and was ascribed to 0-substitution. Kornblum (1975) had obtained the same products. He considered the C- and 0-substitution as Sj l and S 2 reactions, respectively. Dual reactivity of nucleophiles is well known. Since steric hindrance at the reacting carbon prevents S 2 reaction with 4-nitrocumyl chloride, Costentin et al. (1999) concluded that both the C- and 0-substitution products result from an Sr I reaction. 

The solution of the riddle posed by Kornblum s dark Sj l reaction is as follows. The nucleophile does work as a single electron-transfer initiator of the chain process. However, the mechanism of initiation does not consist of a mere outer-sphere electron transfer from the nucleophile to form the anion-radical of the substrate. Rather, it involves a dissociative process in which electron transfer and bond breaking are concerted (Costentin and Saveant 2000). Scheme b at the beginning of Section 7.8 illustrates the concerted mechanism. 

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