With nitrous acid, diazonium salts from

Diazonium salts (Sections 20.6A, 20.6B, 20.7, and 20.8) Salts synthesized from the reaction of primary amines with nitrous acid. Diazonium salts have the structure [R-N N]+ X. Diazonium salts of primary aliphatic amines are unstable and decompose rapidly those from primary aromatic amines decompose slowly when cold, and are useful in the synthesis of substituted aromatics and azo compounds. 

A famous example of a reaction which must be kept cold is the diazotization of anilines to make diazonium salts. The reaction involves treating the amine with nitrous acid (HONO) made from NaN02 and HCl. You need not think about the mechanism at this stage— you will meet it in Chapter 22—but the key point is that the product is a rather unstable but very useful diazonium salt. The diazotization takes place readily at room temperature, but unfortunately so does the decomposition of the product to give a phenol. By lowering the temperature, we supply insufficient energy for the phenol formation, but the diazotization still works just fine. 

Diazonium salts (Sections 20.6A, 20.6B, and20.7) Salts synthesized from the reaction of primary amines with nitrous acid. Diazonium... 

Primary aromatic amines differ from primary aliphatic amines in their reaction with nitrous acid. Whereas the latter yield the corresponding alcohols (RNHj — ROH) without formation of intermediate products see Section 111,123, test (i), primary aromatic amines 3neld diazonium salts. Thus aniline gives phcnyldiazonium chloride (sometimes termed benzene-diazonium chloride) CjHbNj- +C1 the exact mode of formation is not known, but a possible route is through the phenjdnitrosoammonium ion tlius ... 

Arylamines are converted by diazotization with nitrous acid into arenediazonium salts, ArN2+ X-. The diazonio group can then be replaced by many other substituents in the Sandmeyer reaction to give a wide variety of substituted aromatic compounds. Aryl chlorides, bromides, iodides, and nitriles can be prepared from arenediazonium salts, as can arenes and phenols. In addition to their reactivity toward substitution reactions, diazonium salts undergo coupling with phenols and arylamines to give brightly colored azo dyes. 

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... 

The formation of diazonium salts from aromatic primary amines by reaction with nitrous acid undoubtedly involves the intermediate formation of V-nitroso compounds. The Demjanov and Tiffeneau-Demjanov ring expansions also involve V-nitroso compounds [2]. Some V-nitroso compounds have been used as sources of free radicals and as blowing agents. 

Aryl fluorides also may be prepared from arenamines by way of dia-zonium salts if the procedure is slightly modified. The amine is diazotized with nitrous acid in the usual way then fluoroboric acid or afluoroborate salt is added, which usually causes precipitation of a sparingly soluble diazonium fluoroborate. The salt is collected and thoroughly dried, then carefully heated to the decomposition point—the products being an aryl fluoride, nitrogen, and boron trifluoride ... 

Primary aromatic amines on reaction with nitrous acid in the presence of hydrochloric acid (or other mineral acid) at about 0 °C yield diazonium salts as discrete intermediates. The diazonium salts similarly derived from aliphatic primary amines decompose readily even at this temperature to yield the corresponding alcohol (and other products) with the evolution of nitrogen. 

A second method for preparing aryl halides is the Sandmeyer reaction. During a Sandmeyer reaction, a diazonium salt reacts with copper (I) bromide, copper (I) chloride, or potassium iodide to form the respective aryl halide. The diazonium salt is prepared from aniline by reaction with nitrous acid at cold temperatures. 

The nitrosation of primary aromatic amines with nitrous acid (generated in situ from sodium nitrite and a strong acid, such as hydrochloric acid, sulfuric acid, or HBF4) leads to diazonium salts, which can be isolated if the counterion is non-nucleophilic. 

The first 1,2,3-thiadiazole synthesized, 1,2,3-benzothiadiazole, was prepared by diazotiz-ation of o-aminothiophenol with nitrous acid (equation 31) (B-61MI42400), and recently sodium nitrite-acetic acid has been substituted for nitrous acid (B-79MI42400),. Another modification, thermal decomposition of diazonium acetate (34), affords benzothiadiazole in good yield in contrast to the variable yields usually experienced in the diazotization of o-aminothiophenols (equation 32) (78SST(5)43l). Benzothiadiazoles are also available directly from aromatic amines (equation 33) (70JCS(C)2250). Sulfur monochloride reacts with the amine to form a benzothiazothiolium salt which reacts with nitrous acid to yield a chlorinated 1,2,3-benzothiadiazole (35). This process, depending on the aromatic ring substitution, may afford a number of products, and yields are variable. 

R—N=N. This procedure is called diazotization of an amine. Diazonium salts are the most useful products obtained from the reactions of amines with nitrous acid. The mechanism for diazonium salt formation begins with a nucleophilic attack on the nitrosonium ion to form an A-nitrosoamine. 

Arylanthranils (205) have been obtained from 2-aroylbenzamides by Hofmann degradation and subsequent oxidation, using two moles of sodium hypobromite besides (205), some brominated product was isolated. The anthranil (205) could be reduced (Zn/CaCl2)tothe amino-ketone (206), which with nitrous acid gave some 205, as well as the diazonium salt.345... 

The foimation of aromatic diazonium salts from aromatic primary amines is one of the oldest synthetic procedures in organic chemistry. Methods based on nitrosation of amine with nitrous acid in aqueous solution are die best known, but diere are variants which are of particular use widi weakly basic amines and for the isolation of diazonium salts fiom nonaqueous media. General reviews include a book by Saunders and AUen and a survey of preparative methods by Schank. There ate also reviews on the diazotization of heteroaromatic primary amines and on the diazotization of weakly basic amines in strongly acidic media. The diazotization process (Scheme 11) goes by way of a primary nitrosamine. 

The reaction of aromatic amines with nitrous acid is of considerable importance and the formation of diazonium salts from the primary amines is discussed in detail in Section 8.6. Reaction of nitrous acid with secondary amines does not give diazonium salts, but results instead in A -nitrosation. Tertiary amines such as A, A -dimethylaniline do not N-nitrosate, but undergo electrophilic substitution by the nitrosonium cation (NO ) to give A, A -dimethyl-4-nitrosoaniline (Scheme 8.8). 

Fluorodikylammes react with nitrous acid to produce the corresponding unstable fluoroahphatic diazonium ions Placement of the tnfluoromethyl group at a carbon position a, P, or Y to a diazonium ion was used to probe the inductive effect on the chemistry of the transient carbocation resulting from dediazoniation [7] If the fluoroalkyl group is bound to the same carbon as the amino group, conversion to the more stable diazo compound occurs For example, 4-diazo-1,1,1,2,2-pentafluoro-3-pentafluoroethyl-3-tnfluoromethylbutane is obtained from the reaction of the poly-fluoroalkylamine salt with sodium nitnte [S, 9] (equation 8)... 

Salts of primary aromatic amines react with nitrous acid to produce diazonium salts. The reaction is usually performed by adding a cold solution of sodium nitrite to a cold solution of the arylamine in aqueous mineral acid. The end point of the reaction is conveniently determined by the detection of excess nitrous acid with potassium iodide-starch paper. Sulfamic acid has long been used both in industry and in the laboratory to remove excess nitrous acid. It has been found to react with the more active diazo compounds. In most cases, high temperatures are avoided to prevent the formation of phenols and the decomposition of the unstable nitrous acid. An excess of mineral acid is necessary to prevent coupling between the diazonium salt and unreacted amine (cf. method 494). If the amine salt is somewhat insoluble, a fine crystalline form, which is produced by rapid crystallization from a warm aqueous solution, may be employed. ... 

Much of Landsteiner s pioneer work was carried out with haptens that were aromatic amines. The compounds were converted to diazonium salts with nitrous acid and aUowed to react with proteins at alkaline pH (approximately 9). Reaction occurred primarily with histidine, tyrosine, and tryptophan residues of the protein carrier. For a representative procedure, see Kabat (p. 799 seq.). An interesting application of this procedure was the preparation of a chloramphenicol-protein conjugate which was used to elicit antibodies specific for chloramphenicol. In this case, a prior reduction of the nitro group of chloramphenicol to an amino group was required. As early as 1937, carcinogenic compounds were conjugated to protein carriers by means of their isocyanate derivatives which were prepared from amines. Immune sera were raised, and their properties were studied. - ... 

Problem 23.20 (a) Coupling of diazonium salts with primary or secondary aromatic amines (but not with tertiary aromatic amines) is complicated by a side reaction that yields an isomer of the azo compound. Judging from the reaction of secondary aromatic amines with nitrous acid (S. 23.10), suggest a possible structure for this by-product. 

Diphenylamine (8) reacts with nitrous acid to yield iV-nitrosodiphenylamine (180), formerly a useful rubber vulcanization inhibitor. As a toxic nitroso compound, its use is now restricted. The reaction between 8 and acetone yields A-phenylbenzeneamine, a rubber antioxidant. 3-Methyl-phenyl-1-benzenesulfonyltriazene (181) and its toluene analog, both made from the reaction between the diazonium salt of aniline and the corresponding sulfonamide, have been used as blowing agents for rubber. 

---