Properties of diazo compounds

In Westheimer s original photoaffinity labeling experiment, diazoacetyl-chymotrypsin was photolysed. Later, Westheimer s group made the improved diazo reagents listed in Table 3.1. 

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The synthesis and properties of diazo compounds have been covered in an excellent review by Regitz and Maas. This section does not attempt to duplicate that review. Rather, two key areas are covered the most practical methods for the preparation of diazo-containing compounds, and use of these intermediates in organic synthesis. To understand these areas, however, it is important first to appreciate the structure, bonding and reactivity of the diazo functional group. 

Hantzsch now" prepared isomeric diazocyanides (not cyanide and isocyanide) with the same structure C1C6H4 N2 CN, which Bamberger regarded as (A) and (B) compounds (see above). Hantzsch first considered that (B) is incompatible with the properties of diazo-compounds, which have different structures in the solid state and in solution but he then adopted (B) for salts in solution, calling the radical diazonium whilst the solids are yw-diazo-compounds and the diazo-cyanides are stereo-isomers ... 

Nevertheless, a more traditional approach to the stabilization of carbenes and the investigation of their spectral properties deals with the direct generation of carbenes in low-temperature matrices, e.g. by the photolysis of diazo-compounds or ketenes. The method allows stabilization of carbenes in their ground electronic state, prevents intramolecular isomerization and also facilitates direct spectroscopic monitoring of their chemical transformations in low-temperature matrices. 

Constitution.—In the following discussion of the constitution and reactions of diazo compounds diazo benzene and its salts will be taken as examples. The reactions, however, are to be considered as typical of all diazo compounds. The physical properties of free diazo com-... 

The study of the salts of benzenediazo hydroxide has led to the discovery of facts which make it necessary to broaden still further the hypothesis of the structure of diazo compounds. When potassium benzenediazoate is heated with a strong solution of potassium hydroxide, it is converted into an isomeric salt, which is very stable and forms derivatives which differ widely in properties from the analogous derivatives of its isomer. The explanation which has been put forward of the isomerism in this case is based on stereochemical considerations. The arrangement of the atoms in the case of benzenediazo hydroxide is illustrated by the following formulas —... 

The cyclopropanation of olefins of various electronic properties by diazo compounds in the presence of complexes of group 9 metals with porphyrins has been systematically overviewed. " ... 

The diazirines are of special interest because of their isomerism with the aliphatic diazo compounds. The diazirines show considerable differences in their properties from the aliphatic diazo compounds, except in their explosive nature. The compounds 3-methyl-3-ethyl-diazirine and 3,3-diethyldiazirine prepared by Paulsen detonated on shock and on heating. Small quantities of 3,3-pentamethylenediazirine (68) can be distilled at normal pressures (bp 109°C). On overheating, explosion followed. 3-n-Propyldiazirine exploded on attempts to distil it a little above room temperature. 3-Methyldiazirine is stable as a gas, but on attempting to condense ca. 100 mg for vapor pressure measurements, it detonated with complete destruction of the apparatus." Diazirine (67) decomposed at once when a sample which had been condensed in dry ice was taken out of the cold trap. Work with the lower molecular weight diazirines in condensed phases should therefore be avoided. 

The properties of the diazirines and the analytical results showed that a new class of isomeric diazo compounds had been discovered. The three-membered ring structure (65), which is made probable by the synthetic methods, is confirmed by the reactions of the diazirines. 

The proof of the three-membered structure of the diazirines concludes the discussion on the three-membered ring structure of the aliphatic diazo compounds. The knowm linear aliphatic diazo compounds and the newly prepared cyclic diazo compounds (diazirines) are two independent classes of compounds completely different in their physical and chemical properties. An interconversion of the linear and cyclic diazo compounds has not so far been possible. 

Gothelf presents in Chapter 6 a comprehensive review of metal-catalyzed 1,3-di-polar cycloaddition reactions, with the focus on the properties of different chiral Lewis-acid complexes. The general properties of a chiral aqua complex are presented in the next chapter by Kanamasa, who focuses on 1,3-dipolar cycloaddition reactions of nitrones, nitronates, and diazo compounds. The use of this complex as a highly efficient catalyst for carbo-Diels-Alder reactions and conjugate additions is also described. 

Whereas the utility of these methods has been amply documented, they are limited in the structures they can provide because of their dependence on the diazoacetate functionality and its unique chemical properties. Transfer of a simple, unsubstituted methylene would allow access to a more general subset of chiral cyclopropanes. However, attempts to utilize simple diazo compounds, such as diazomethane, have never approached the high selectivities observed with the related diazoacetates (Scheme 3.2) [4]. Traditional strategies involving rhodium [3a,c], copper [ 3b, 5] and palladium have yet to provide a solution to this synthetic problem. The most promising results to date involve the use of zinc carbenoids albeit with selectivities less than those obtained using the diazoacetates. 

Bis(diazo)-l,2,4,5-cyclohexanetetraone (4.5) may be regarded as a derivative of a double 1,2-quinone diazide. Its X-ray analysis was reported by Ansell (1969). The synthesis, properties, and structure of this interesting compound will be discussed in the forthcoming book on aliphatic diazo compounds (Zollinger, 1995, Secs. 2.3 and 5.2). 

Quinone diazides (12.9) and their 1,2-isomers (Secs. 1.2, 2.4, and 4.2) simultaneously display the properties of both aliphatic and aromatic diazo components. They can be considered as analogues of conjugated diazoketones. On the other hand, a specific feature of many of their reactions is their conversion to hydroxyarenediazo-nium ions (12.8) in the presence of acids (Scheme 12-7). The p Ta-value of the 4-hydroxybenzenediazonium ion is 3.19 (Kazitsyna and Klyueva, 1972), so the reactivity of compounds of this type will depend considerably on the acidity of the reaction medium. Compound 12.8 is much more electrophilic than 12.9, and therefore the measured rate depends on the position of the equilibrium in Scheme 12-7. 

Another remarkable property of iodorhodium(III) porphyrins is their ability to decompose excess diazo compound, thereby initiating carbene transfer reactions 398). This observation led to the use of iodorhodium(III) me.vo-tetraarylporphyrins as cyclopropanation catalysts with enhanced syn anti selectivity (see Sect. 2.2.3) s7, i°o) as wep as catalysts for carbenoid insertion into aliphatic C—H bonds, whereby an unusually high affinity for primary C—H bonds was achieved (see Sect. 6.1)287). These selectivities, unapproached by any other transition metal catalyst,... 

Carbenes are commonly generated by irradiation or pyrolysis of an appropriate diazo-compound (2). Apart from differences readily traced to the change in temperature, the chemical properties of the carbenes formed from photolysis and from thermolysis are usually quite similar. These observations... 

The diazo-compounds and corresponding aromatic carbenes that form the basis for our dissection of structure and reactivity are shown in Table 1. The carbenes in this group are carefully chosen so that the variation in structure is systematic the theory identifies the carbene bond angle and certain electronic factors as controlling chemical and physical properties, and as far as possible, these two features are varied independently of each other for these carbenes. Table 2 lists some other aromatic carbenes that have been studied. In general, the structures of these carbenes are not simply related to each other. Nevertheless, the principles uncovered by analysis of the compounds of Table 1 can be readily extended to those of Table 2. 

Shortly after Perkin had produced the first commercially successful dyestuff, a discovery was made which led to what is now the dominant chemical class of dyestuffs, the azo dyes. This development stemmed from the work of Peter Griess, who in 1858 passed nitrous fumes (which correspond to the formula N203) into a cold alcoholic solution of 2-aminO 4,6 dinitrophenol (picramic acid) and isolated a cationic product, the properties of which showed it to be a member of a new class of compounds [1]. Griess extended his investigations to other primary aromatic amines and showed his reaction to be generally applicable. He named the products diazo compounds and the reaction came to be known as the diazotisation reaction. This reaction can be represented most simply by Scheme 4.1, in which HX stands for a strong monobasic acid and Ar is any aromatic or heteroaromatic nucleus. 

Nor can there be any question of real tautomerism in the case of phenol. In its chemical properties phenol resembles the aliphatic enols in all respects. We need only recall the agreement in the acid character, the production of colour with ferric chloride, and the reactions with halogens, nitrous acid, and aromatic diazo-compounds (coupling), caused by the activity of the double bond and proceeding in the same way in phenols and aliphatic enols. The enol nature of phenol provides valuable support for the conception of the constitution of benzene as expressed in the Kekule-Thiele formula, since it is an expression of the tendency of the ring to maintain the aromatic state of lowest energy. In this connexion the hypothetical keto-form of phenol (A)—not yet obtained—would be of interest in comparison with... 

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