Diazonium ions generation

Primary arylamines like primary alkylammes form diazonium ion salts on nitro sation Aryl diazonium 10ns are considerably more stable than their alkyl counterparts Whereas alkyl diazonium 10ns decompose under the conditions of their formation aryl diazonium salts are stable enough to be stored m aqueous solution at 0-5°C for a rea sonable time Loss of nitrogen from an aryl diazonium ion generates an unstable aryl cation and is much slower than loss of nitrogen from an alkyl diazonium ion... 

One of the best leaving groups is molecular nitrogen in alkyl diazonium ions. Diazonium ions are generated by nitrosation of primaiy amines. The diazonium ions generated from alkyl amines are veiy unstable and immediately decompose with loss of nitrogen. 

FIGURE 22.5 The diazonium ion generated by treatment of a primary alkylamine with nitrous acid loses nitrogen to give a carbocation. The isolated products are derived from the carbocation and include, in this example, alkenes (by loss of a proton) and an alcohol (nucleophilic capture by water). 

Diazonium ions generated from ordinary aliphatic primary amines are usually useless for preparative purposes, since they lead to a mixture of products giving not only substitution by any nucleophile present, but also elimination and rearrangements if the substrate permits. For example, diazotization of n-butylamine gave 25% 1-butanol, 5.2% 1-Chlorobutane, 13.2% 2-butanol, 36.5% butenes (consisting of 71% 1-butene, 20% trans-2-butene, and 9% cw-2-butene), and traces of butyl nitrites. ... 

Other alkanediazonium ions, including the bridgehead bicyclo[2.2.1]heptane-l-diazonium ion 9, do not undergo azo coupling reactions but give only nucleophilic substitution productsIn addition to the examples given above, some alkene-diazonium ions generated from nitrosooxazolidones can also add azide ions ... 

The radical-generating step is a special case of the decomposition of an azo compound. An important use for this reaction is in the synthesis of biphenyls, by reactions in which a second aromatic molecule is attacked by the aryl radical. Under these conditions, hydrogen abstraction from the intermediate arylcyclohexadienyl radical becomes part of the chain mechanism, with the aryl diazonium ion oxidizing the radical intermediate to give the biphenyl. Aryl diazonium ions generated in the usual way by diazotization of aryl amines can also serve as sources of aryl radicals. Substituted biphenyls can be synthesized by base-catalyzed decomposition of the diazonium salt, usually in the presence of an excess of the aromatic substrate. 

The main drawback to this reaction is the toxicity of diazomethane and some of its precursors. One possible alternative is the use of alkyltriazenes as reactive alkylating agents. Alkyltriazenes are readily prepared from primary amines and aryl diazonium salts. The triazenes, on being protonated by the carboxylic acid, generate a reactive alkylating agent that is equivalent, if not identical, to the alkyl diazonium ions generated from diazoalkanes. 

Because a neutral molecule is eliminate4 rather than an anion, there is no electrostatic attraction (ion pairing) between the products of the dissociation step. As a result, the carbocations generated by diazonium-ion decomposition frequently exhibit somewhat different behavior from those generated from halides or sulfonates under solvolytic conditions. ... 

Nucleophilic substitution reactions that occur imder conditions of amine diazotization often have significantly different stereochemisby, as compared with that in halide or sulfonate solvolysis. Diazotization generates an alkyl diazonium ion, which rapidly decomposes to a carbocation, molecular nitrogen, and water ... 

Among the reagents that are classified as weak electrophiles, the best studied are the aromatic diazonium ions, which reagents react only with aromatic substrates having strong electron-donor substituents. The products are azo compounds. The aryl diazonium ions are usually generated by diazotization of aromatic amines. The mechanism of diazonium ion formation is discussed more completely in Section 11.2.1 of Part B. 

Packer and Richardson (1975) and Packer et al. (1980) made use of the fact that electrons can be generated in water by y-radiation from a 60Co source (Scheme 8-29) to induce a free radical chain reaction between diazonium ions and alcohols, aldehydes, or formate ion. It has to be emphasized that the radiolytically formed solvated electron in Scheme 8-29 is only a part of the initiation steps (Scheme 8-30) by which an aryl radical is formed. The aryl radical initiates the propagation steps shown in Scheme 8-31. Here the alcohol, aldehyde, or formate ion (RH2) is the reducing agent (i.e., the electron donor) for the main reaction. The process is a hydro-de-diazoniation. 

In principle it should be possible to predict quantitatively the reactivity of such species containing nucleophilic homolytic leaving groups towards diazonium ions, by using a dual parameter equation. One parameter serves as a measure of the donor property of the particle the other parameter is the redox potential. However, the complex nature of kinetics of homolytic dediazoniations is likely to be a great obstacle in attempts to calculate rate constants referring only to the radical-generation step. 

No matter how produced, RN2 are usually too unstable to be isolable, reacting presumably by the SnI or Sn2 mechanism. Actually, the exact mechanisms are in doubt because the rate laws, stereochemistry, and products have proved difficult to interpret. If there are free carbocations, they should give the same ratio of substitution to elimination to rearrangements, and so on, as carbocations generated in other SnI reactions, but they often do not. Hot carbocations (unsolvated and/or chemically activated) that can hold their configuration have been postulated, as have ion pairs, in which OH (or OAc , etc., depending on how the diazonium ion is generated) is the coun-... 

In each case the mechanism involves generation of an aryl radical from a covalent azo compound. In acid solution diazonium salts are ionic and their reactions are polar. When they cleave, the product is an aryl cation (see p. 852). However, in neutral or basic solution, diazonium ions are converted to covalent compounds, and these cleave to give free radicals ... 

This seeming unreactivity of vinyl halides in solvolytic processes and the lack of availability of more reactive precursors, such as sulfonate esters, until recently has discouraged early attempts at mechanistic investigations of vinyl cations generated by solvolyses. However, vinyl cations have been generated via vinyl diazonium ions derived from various precursors. 

Rearrangements Involving Diazonium Ions. Aminomethyl carbinols yield ketones when treated with nitrous acid. The reaction proceeds by formation and rearrangement of diazonium ions. The diazotization reaction generates the same type of (J-hydroxycarbocalion that is involved in the pinacol rearrangement. 

The first widely used intermediates for nucleophilic aromatic substitution were the aryl diazonium salts. Aryl diazonium ions are usually prepared by reaction of an aniline with nitrous acid, which is generated in situ from a nitrite salt.81 Unlike aliphatic diazonium ions, which decompose very rapidly to molecular nitrogen and a carbocation (see Part A, Section 4.1.5), aryl diazonium ions are stable enough to exist in solution at room temperature and below. They can also be isolated as salts with nonnucleophilic anions, such as tetrafluoroborate or trifluoroacetate.82 Salts prepared with 0-benzenedisulfonimidate also appear to have potential for synthetic application.83... 

In addition to the aqueous method for diazotization in aqueous solution, diazonium ions can be generated in organic solvents by reaction with alkyl nitrites. 

Good yields of chlorides have also been obtained for reaction of isolated diazonium tetrafluoroborates with FeCl2-FeCl3 mixtures.100 It is also possible to convert anilines to aryl halides by generating the diazonium ion in situ. Reaction of anilines with alkyl nitrites and Cu(II) halides in acetonitrile gives good yields of aryl chlorides and bromides.101... 

The reaction can be carried out efficiently using aryl diazonium tetrafluoroborates with crown ethers, polyethers, or phase transfer catalysts.103 In solvents that can act as halogen atom donors, the radicals react to give aryl halides. Bromotrichloromethane gives aryl bromides, whereas methyl iodide and diiodomethane give iodides.104 The diazonium ions can also be generated by in situ methods. Under these conditions bromoform and bromotrichloromethane have been used as bromine donors and carbon tetrachloride is the best chlorine donor.105 This method was used successfully for a challenging chlorodeamination in the vancomycin system. 

Scheme 11.7 illustrates some arylation of alkenes by diazonium ions. Entries 1 to 4 are typical conditions. Entry 5 illustrates generation of the diazonium ion under in situ conditions. Entry 6 is an example of the reductive conditions using Ti(III). 

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