Diazotization reactions

Manufacture of Dyes and Pigments and pH Adjustment, Use of sulfamic acid in the manufacture of dyes and pigments involves removal of excess nitrite from diazotization reactions (see Azo DZ s) and is based on the following reaction ... 

Peter Griess synthesized the first azo dye soon after his discovery of the diazotization reaction in 1858. The two reactions which form the basis for azo dye chemistry are diazotization (eq. 1) and coupling (eq. 2) (2). 

Barium nitrite [13465-94-6] Ba(N02)2, crystallines from aqueous solution as barium nitrite monohydrate [7787-38-4], Ba(N02)2 H2O, which has yellowish hexagonal crystals, sp gr 3.173, solubihty 54.8 g Ba(NO2)2/100 g H2O at 0°C, 319 g at 100°C. The monohydrate loses its water of crystallization at 116°C. Anhydrous barium nitrite, sp gr 3.234, melts at 267°C and decomposes at 270 °C into BaO, NO, and N2. Barium nitrite may be prepared by crystallization from a solution of equivalent quantities of barium chloride and sodium nitrite, by thermal decomposition of barium nitrate in an atmosphere of NO, or by treating barium hydroxide or barium carbonate with the gaseous oxidiation products of ammonia. It has been used in diazotization reactions. 

Synthesis. Almost without exception, azo dyes ate made by diazotization of a primary aromatic amine followed by coupling of the resultant diazonium salt with an electron-rich nucleophile. The diazotization reaction is carried out by treating the primary aromatic amine with nitrous acid, normally generated in situ with hydrochloric acid and sodium nitrite. The nitrous acid nitrosates the amine to generate the N-nitroso compound, which tautomerizes to the diazo hydroxide. 

A related diazotization reaction involving the supposed peri-aminolepidine (357) to give the unknown phenalene type system (297) was later shown to be incorrect due to wrong orientation of the amino substituent (42JA2417). 

The treatment of 3-amino-1,2,4-triazine 2-oxides 1 or 3-amino-1,2,4-benzotri-azine 1-oxides 29 with nitrous acid proceeds as a diazotization reaction, but the diazo compounds have never been isolated owing to the easy displacement of the di-azo group with nucleophiles. Thus the reaction of 3-amino-1,2,4-triazine 2-oxides 1 with sodium nitrite in hydrochloric or hydrobromic acids leads to the corresponding 3-halogen-1,2,4-tiiazine 2-oxides 119 or 3-bromo-l,2,4-benzotriazine 1-oxides 120 (77JOC546, 82JOC3886). 

Although the diazotization reaction takes place in acidic solution, it is the free amine that reacts, and not the ammonium salt ArNH3+ X . Even in acidic solution there is a small amount of free amine present, since aromatic amines are relatively weak bases. 

Aliphatic primary amines also undergo the diazotization reaction in weakly acidic solution however the resulting aliphatic diazonium ions are generally unstable, and easily decompose into nitrogen and highly reactive carbenium ions. The arenediazonium ions are stabilized by resonance with the aromatic ring ... 

Most functional groups do not interfere with the diazotization reaction. Since aliphatic amines are stronger bases and therefore completely protonated at a pH < 3, it is possible that an aromatic amino group is converted into a diazonium group, while an aliphatic amino group present in the same substrate molecule is protected as ammonium ion and does not react. ... 

For the in situ preparation of the required arenediazonium salt from an aryl amine by application of the diazotization reaction, an acid HX is used, that corresponds to the halo substituent X to be introduced onto the aromatic ring. Otherwise—e.g. when using HCl/CuBr—a mixture of aryl chloride and aryl bromide will be obtained. The copper-(l) salt 2 (chloride or bromide) is usually prepared by dissolving the appropriate sodium halide in an aqueous solution of copper-(ll) sulfate and then adding sodium hydrogensulfite to reduce copper-(ll) to copper-(1). Copper-(l) cyanide CuCN can be obtained by treatment of copper-(l) chloride with sodium cyanide. 

The reaction of nitrous acid with the amino group of the /3-amino alcohol—e.g. 1-aminomethyl-cyclopentanol 1—leads to formation of the nitrosamine 4, from which, through protonation and subsequent loss of water, a diazonium ion species 5 is formed " —similar to a diazotization reaction ... 

Curtius rearrangement, 933 diazotization reaction, 941 Gabriel amine synthesis, 929 heterocycle, 945... 

Diazoquinone-novolac resist, 506 Diazotization reaction, 941 DIBAH, see Diisobutylaluminum hydride... 

In all the diazotization reactions discussed in Sections 2.1-2.4 an equimolar amount of water is formed as byproduct. There are two general pathways for obtaining diazonium salts without formation of water. One is based on the rearrangement of 7V-nitroso-7V-arylacetamides, the other on the nitrosation of a monoarylated sp2-hybridized nitrogen compound by nitrosating reagents XNO in which X is a weak nucleophile. 

The diazotization reaction can also be initiated via the vapor phase, e. g. with ethyl nitrite that can be generated in one trough of a twin-trough chamber by adding a few drops of cone, hydrochloric acid to a mixture of ethanol and saturated aqueous sodium nitrite solution (1 + 1) [3] the less volatile amyl nitrite can be used as an alternative [3]. 

The rates are very fast and comparable with those of diazotization reactions. They vary with the nature of the isomer in the order 3 > 4 > 2. 

Diazotization reactions diazonium salt and amine instabiiity... 

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 important event in the history of azo pigments was the discovery of the diazotization reaction by P. Cries in 1858. In 1875, Caro and Witt synthesized chrysoidine,... 

The diazotization reaction typically involves an aromatic amine, such as a mono-, di-, or trisubstituted aniline, as a diazo component. Coupling components are also frequently based on aniline or its derivatives. The following examples are thus important diazo components ... 

The list of important diazo components for the diazotization reaction includes aniline and a number of aniline derivatives, diamino diphenyl derivatives, and aromatic aminosulfonic acids. Important coupling components are acetoacetic arylides, pyrazolones, (3-naphthol, 2-hydroxy-3-naphthoic acid, and their aniline derivatives. 

The reaction proceeds via two main steps a diazotization reaction, which is the basis of diazonium salt formation, followed by azo coupling, which is responsible for the formation of the azo compound. 

On an industrial scale, diazotization reactions are carried out by dissolving the aromatic amine in hydrochloric or sulfuric acid. Despite the fact that 2 equivalents of acid per equivalent of amino group should theoretically suffice, as much as 2.5 to 3 equivalents per amino function are actually required to ensure complete diazonium salt formation. One equivalent of an aqueous sodium nitrite solution is added to the resulting mixture at 0 to 5°C. The exothermic nature of the reaction, combined with the heat sensitivity of most diazonium salts, makes it necessary to provide cooling, usually by direct addition of ice. 

The diazotization reaction requires an excess of acid formation of the active ni-trosating agent XNO proceeds via the underlying equilibrium ... 

Amines which are considerably or entirely insoluble in water are dissolved in glacial acetic acid or in other organic media, possibly mixed with water e.g., alcohols or aprotic solvents. Addition of acid is followed by a typical diazotization reaction in an aqueous sodium nitrite solution. Other possible sources of the nitrosating species NO include nitrosylsulfuric acid, nitrosylchloride, alkylnitrite, and nitrous gases. 

The outcome of a diazotization reaction is largely controlled by the temperature, the pH, and the concentration of the medium in which the reaction is carried out. Reactions involving sparingly soluble amines are also dependent on physical parameters, such as distribution and particle size, as well as on the possible presence of emulsifiers or dispersion agents. 

On an industrial scale, diazotization reactions are chiefly carried out in cast iron kettles that are lined with brick or rubber as a protection against acid. Wooden vats also continue to be used. 

What is the diazotization reaction How does it help in the assay of drugs Explain. 

Based on the diazotization reaction how would you carry out the assay of the following drug substances ... 

The nucleotide 5-astato-2-deoxyuridine has been obtained from 2-deoxyuridine in a manner similar to that described for preparing 5-astatouridine with a radiochemical yield of 85% (170). Attempts to synthesize 5-astato-2-deoxyuridine from the diazonium salt of 5-amino-2-deoxyuridine led only to a 2-3% yield of desired product, whereas 20-25% of the bound astatine was found in the form of 5-astatouracil (99,123). This was apparently due to hydrolysis of the 7V-glycosyl bond in the course of the diazotization reaction. The final product, 5-astato-2-deoxyuridine, was identified by TLC, paper electrophoresis (170), and HPLC (99,122,123). 

The most traditional method used to obtain diazo compounds involves the diazotization reaction of an amino group, followed by neutralization of... 

An example of a diazotization reaction of a tosylaminotriazole in sulfuric acid has been reported to give the corresponding diazo compound, following hydrolysis of the tosyl group (75LA2159). 

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