Rosenmund-von Braun reactions

A common method for the preparation of alkyl cyanide 2 is the treatment of corresponding alkyl halides 1 with cyanide. The corresponding reaction with aromatic substrates is called the Rosenmund-von-Braun reaction. 

A second reaction which is very often used for the preparation of phthalonitriles, although the yields are usually not reproducible, is the Rosenmund-von Braun reaction (see Houben-Weyl, Vol. E5, p 1460).106 107 Herein, a benzene derivative with a 1,2-dibromidc or 1,2-dich-loride unit is treated with copper(I) cyanide in dimethylformamidc or pyridine. During this reaction the formation of the respective copper phthalocyanine often occurs. This can be used as an easy procedure for the exclusive synthesis of copper phthalocyanines (see Section 2.1.1.7.),1 os-109 but can also lead to problems if the phthalonitrile is required as the product. For example, if l,2-dibromo-4-trifluoromethyl-benzene is subjected to a Rosenmund-von Braun reaction no 4-trifluoromethylphthalonitrile but only copper tetra(tri-fluoromethyljphthalocyanine is isolated.110... 

Both 4,5- and 3,6-disubstituted phthalonitriles are commonly used to prepare phthalocyanines with liquid crystalline properties. An example of the Rosenmund-von Braun reaction is shown below.107... 

Due to its commercial importance, the synthesis of copper phthalocyanine (PcCu) is the best investigated of all the phthalocyanines. Copper phthalocyanine is prepared from phthalonitrile and copper(I) chloride without solvent137 and also in a melt of urea.229,277 Additionally, the insertion of copper into metal-free phthalocyanine in butan-l-ol and pentan-l-ol is possible. The copper salts used in this case are copper(I) chloride112 and copper(II) acetate.290 Starting from copper(II) acetate, copper phthalocyanine can also be prepared in ethylene glycol.127 As mentioned above, copper phthalocyanine often occurs as a byproduct of the Rosenmund-von Braun reaction. To increase the yield of the phthalocyanine the solvent dimethylformamide can be substituted by quinoline. Due to the higher boiling point of quinoline, the copper phthalocyanine is the main product of the reaction of copper(I) cyanide and 1,2-dibromoben-zene.130... 

A microwave-assisted variant of the Rosenmund von Braun reaction has also been developed (Scheme 73) [83]. DMF at 200 °C proved not very useful for the cyanodehalogenation of methyl (3R)-6-bromo-5-oxo-2,3-dihydro-5ff-[l,3]thiazolo[3,2-a]pyridine-3-carboxylates since only low yields of the corresponding nitrile were obtained, and there were substantial amoimts of unconverted starting material. Extending the reaction time from 10 to 20 min gave more desired reaction product but also significant amoimts of... 

These modified Rosenmund von Braun reaction conditions were also used by Gopalsamy et al. for the rapid cyanation of the 1,3,4,9-tetrahydropyrano-[3,4-fc]indole skeleton while searching for potent and selective Hepatitis C virus polymerase inhibitors (Scheme 74) [84]. 

For more than a century, stoichiometric methods were presumed in the preparation of benzonitriles in laboratory and industry. These particularly include the Rosenmund-von Braun reaction of aryl halides, the diazotization of anilines and subsequent Sandmeyer reaction, and the ammoxidation. Because of (over)stoichiometric amounts of metal waste, lack of functional group tolerance, and harsh reaction conditions, these methods do not meet the criteria of modern sustainable synthesis. 

Following the reports of sulfur appended porphyrazines, Fitzgerald et al. (28) reported a facile synthesis of alkyl appended porphyrazines in 1991, preparing the dialkyl dinitrile precursors from alkynes via a Rosenmund von Braun reaction. Later, these types of dinitriles were used in mixed cyclizations to prepare porphyrazines with three dipropyl substituents (6,29). An intriguing extension was the... 

A bromine atom on the benzene ring of chromones takes part in the Rosenmund-von Braun reaction to give moderately good yields of the nitrile, for example ethyl 8-cyano-6-methylchromone-2-carboxylate (545) (72JCS(Pl)779). Iodochromones and iodoflavones undergo the Ullmann reaction to form bis-compounds, some of which occur naturally or are related to such biflavonoids (B-75MI22302, 72JMC583). 

Side Note 16.2. Figure 16.8 shows a nucleophilic aromatic substitution reaction conducted with copper Rosenmund-von-Braun cyanide. This Rosenmund-von-Braun reaction is not included among the numerous Ull-... 

The reaction between aryl halides and cuprous cyanide is called the Rosenmund-von Braun reaction Reactivity is in the order I > Br > Cl > F, indicating that the SNAr mechanism does not apply. Other cyanides (e.g., KCN and NaCN) do not react with aryl halides, even activated ones. This reaction has been done in ionic liquids using CuCN. ° The reaction has also been done in water using CuCN, a phase transfer catalyst, and microwave irradiation. 

As a classical technique for the synthesis of aromatic cyanides treatment of the corresponding halides with CuCN has to be cited (Rosenmund-von Braun reaction). It is carried out at 15C1-250 C, either without any solvent at all, or using pyridine or quinoline, which also operate as complexing agents for the CuCN. Other heavy metal cyanides or hexacyanoferrates have been used in principle, but their... 

Conventional organic synthesis for aromatic nitriles [e. g. 10], for example the Rosenmund-von Braun reaction, the Sandmeyer reaction, or the oximation of aldehydes in the presence of dehydrating agents, performed in batch processes, are cumbersome and result in different amounts of by- and waste products. The ineffectiveness of such processes with regard to the amount of feedstock necessary per formed nitrile and the waste produced is rather high (in terms of the effectiveness factor defined by Sheldon [11]). 

Aryl halides are inert to reaction with cyanide ion under normal Sn2 conditions (chap. 2, sec. 2.11), but they do reaet when heated with cuprous salts like cuprous cyanide (CuCN). Reaction of 1-bromonaphthalene (13) with CuCN at 202°C gave an 89% yield of the aryl nitrile (14). This transformation is called the Rosenmund-von Braun reaction and can be applied to a wide range of aryl halides. The aryl nitriles produced can be used in a variety of reactions. This transformation does not work when potassium or sodium cyanide is used. An amine base is usually added to facilitate the reaction. 

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