Sandmeyer reaction

\( \newcommand\) No headers Each of the following three reactions of aromatic Each reaction, overall, is a nucleophilic substitution. None of the reactions, however, occurs in the absence of copper (I) ion, which is a reducing agent. The mechanism of Sandmeyer reactions is not fully understood. • • Gamini Gunawardena from the

Sandmeyer Reaction Mechanism What Is the Sandmeyer Reaction? The Sandmeyer reaction is a type of substitution reaction that is widely used in the production of aryl halides from aryl diazonium salts. Copper salts like chloride, bromide or iodide ions are used as catalysts in this reaction. Notably, the Sandmeyer reaction can be used to perform unique transformations on benzene. The transformations include hydroxylation, trifluoromethylation, cyanation, and halogenation. Table of Contents • • • • • • The reaction was first discovered in the year 1884, when Traugott Sandmeyer, a Swiss chemist, was conducting an experiment to synthesise phenylacetylene from benzene diazonium chloride and cuprous acetylide. However, at the end of the experiment, he obtained phenyl chloride as the main product. The Sandmeyer reaction is believed to be a great example of a The Sandmeyer Reaction Mechanism The Sandmeyer reaction follows a free radical mechanism. The reaction is actually a two-step process, where the synthesis of To elucidate further, the Sandmeyer reaction mechanism commences with a transfer of a single electron from the copper to the diazonium. This results in the formation of a non-participating diazo radical as well as copper(II) halide. A molecule of nitrogen gas is then released by the diazo radical to give aryl radical, which then reacts with the copper(II) halide to restore the Sandmeyer Reaction Mechanism Formation of Nitrosonium Ion We will look at the Sandmeyer reaction...

\( \newcommand\) • • • Aryl diazonium salts are important intermediates. They are prepared in cold (0 º to 10 ºC) aqueous solution, and generally react with nucleophiles with loss of nitrogen. Some of the more commonly used substitution reactions are shown in the following diagram. Since the leaving group (N 2) is thermodynamically very stable, these reactions are energetically favored. Those substitution reactions that are catalyzed by cuprous salts are known as 4 (–), a reaction known as the Schiemann reaction. Stable diazonium tetrafluoroborate salts may be isolated, and on heating these lose nitrogen to give an arylfluoride product. The top reaction with hypophosphorus acid, H 3PO 2, is noteworthy because it achieves the reductive removal of an amino (or nitro) group. Unlike the nucleophilic substitution reactions, this reduction probably proceeds by a radical mechanism. These aryl diazonium substitution reactions significantly expand the tactics available for the synthesis of polysubstituted benzene derivatives. Consider the following options: • The usual precursor to an aryl amine is the corresponding nitro compound. A nitro substituent deactivates an aromatic ring and directs electrophilic substitution to meta locations. • Reduction of a nitro group to an amine may be achieved in several ways. The resulting amine substituent strongly activates an aromatic ring and directs electrophilic substitution to ortho & para locations. • The activating character of an amine su...

\( \newcommand\) • • • • • • • • • Objectives After completing this section, you should be able to • • identify the product formed when a given arylamine is reacted with aqueous bromine. • give an appropriate example to illustrate the high reactivity of arylamines in electrophilic aromatic substitution reactions. • explain why arylamines cannot be used in Friedel‑Crafts reactions. • • show how the problems associated with carrying out electrophilic aromatic substitution reactions on arylamines can be circumvented by first converting the amine to an amide, and illustrate this process with an appropriate example. • outline a possible synthetic route for the preparation of a given sulfa drug. • identify the starting material, the necessary organic reagents, inorganic reagents, or both, and the intermediate compounds formed during the synthesis of a given sulfa drug. • design a multi‑step synthesis for a given compound in which it is necessary to protect the amino group by acetylation. • • write a general equation to describe the formation of an arenediazonium salt. • identify the product formed when a given arenediazonium salt is reacted with any of the following compounds: copper(I) chloride, copper(I) bromide, sodium iodide, copper(I) cyanide, hot aqueous acid, hypophosphorous acid. • identify the arenediazonium salt, the inorganic reagents, or both, needed to produce a given compound by a diazonium replacement reaction. • • illustrate, with appropriate examples, the import...

\( \newcommand\) • • • • • • • • • • • • • • • • • • • • • • Alkanediazonium salts are very unstable; therefore, arenediazonium salts are often simply referred to as diazonium salts. As is mentioned in the textbook, arenediazonium salts are very useful intermediates from which a wide variety of aromatic compounds can be prepared. You should be thoroughly familiar with the use of diazonium salts to prepare each of the classes of compounds. In addition, you should be aware that fluoroarenes can also be prepared from diazonium salts, as follows: Making the aromatic ring available for attack by nucleophiles Most preparations of aromatic compounds we have seen (such as ortho or para to a leaving group. The most versatile way to make aromatic rings available for nucleophilic attack is to prepare arenediazonium salts, containing the ArN 2 + ion. The diagram below shows the variety of reactions possible with arenediazonium salts. Arenediazonium salts are easily prepared from arylamines (anilines) using a process called diazotization. The process involves dissolving the amine in a suitable acid, cooling in an ice bath to 0-5 oC, then adding sodium nitrite (NaNO 2) solution. The acid reacts with the NaNO 2 to form nitrous acid (HNO 2), which then reacts with the arylamine to form the arenediazonium salt. The most common salt to use for these reactions is the chloride (made using HCl as the acid), which are fairly soluble but decompose rapidly at room temperature. However, in some re...