Diazo initiators

As the functionality of the (acrylic ester-diene) copolymers l8,19> is higher than two, the disproportionation mechanism is unimportant and may be neglected. That means that in the diazo-initiated polymerization, termination mostly takes place by recombination. 

The initiator should be a hydroxyl-containing molecule (i.e., diazo or peroxide) because the chain transfer to a hydroxylated solvent (alcohol) leads to less than two OH groups per chain 144). However, contrary to the initiation by hydrogen peroxide, the polymers obtained using a diazo initiator have well-defined chain ends and functionality close to 2, with some monofunctional (0-6%) and trifunctional (1-7%) chains 22). With H202, the functionality of HTPB increases with molecular weight121 l03) or is fairly constant for 1000 < M < 4000 I34) or 1500 < M < 3000, 03) (Figs. 

Amidinyl radicals 1166 are readily generated from amidoxime benzoates, for example, 1165, by treatment with a stannane-diazo initiator or with Ni-AcOH and captured by an internal olefin to give the corresponding imidazoline 1167. Interestingly, the use of allyl tri- -butylstannane in the case of substrate 1168 results in the clean formation of allyl imidazoline 1169. As expected, allylation occurs from the least hindered exo face to give the isomer shown (Scheme 284) <2003CC1870> (ACCN = l,l -azobis(cyclohexanecarbonitrile)). 

First, Ghatge et al. [23] obtained a diazo initiator which is a precursor of isocyanate according to the followir reactions ... 

In a similar way, Hawker and Hedrick [220] synthesized a-amino,cw-aminoxyl PS. Before performing the NMP of styrene, they synthesized a new protected amino diazoic initiator by reaction of N-(ferf-butoxycarbonyl)-4-aminophenol with a bisacid chloride diazo initiator. The resulting initiator was heated in the presence of styrene and TEMPO at 130 °C (Scheme 37). 

This kinetic approach is generally used to study free radical oxidation in simple model systems. However, the azo initiators used in these studies are artificial systems that are not found in either foods or biological systems. The efficiency of these initiators is greatly affected by the lipid systems used for oxidation and by the solvent viscosity the more viscous the solvent the lower their efficiency. The efficiency of initiators in escaping the solvent cage varies DMVN is about 75% efficient whereas AIBN is 65% efficient. The diazo hydroperoxides (AOOH) formed by reaction (20) are known to interfere with the HPLC analyses of lipid hydroperoxides. Diazo initiators produce a big flux of peroxyl radicals that do not have time to branch and proceed to other reactions observed in real lipid systems. The quantitative kinetic data obtained with diazo initiators may thus be oversimplified and not relevant to either foods or biological systems. 

In the decomposition of diazo initiators, the number of free radicals in the bulk solutions is estimated to be less than two for each molecule of initiator consumed. This cage effect is dependent on the solvent viscosity. The more... 

In contrast to solution, the higher viscosity of a lecithin liposome decreases the efficiency of free radical initiation, and retards their autoxidation. Artificial azo initiators have a very low efficiency (about 9%) when solubilized in the bilayer phase. For this reason, the oxidizability of lecithin dispersed in a liposome is much lower than in solution. Although the solvent cage effect may be unique to diazo initiators commonly used in kinetic studies, and is not necessarily relevant to food lipid systems, metal initiators which are relevant to foods and biological systems, may also be affected by solvent cage effects because of the hydrated layer in emulsions (Figure 10.4). 

Bam ford-Stevens Reaction- initial conversion of a tosylhydrazone to a diazo intermediate... 

More definitive evidence for the formation of an oxirene intermediate or transition state was presented recently by Cormier 80TL2021), in an extension of his earlier work on diazo ketones 77TL2231). This approach was based on the realization that, in principle, the oxirene (87) could be generated from the diazo ketones (88) or (89) via the oxocarbenes 90 or 91) or from the alkyne (92 Scheme 91). If the carbenes (90) (from 88) and (91) (from 89) equilibrate through the oxirene (87), and if (87) is also the initial product of epoxidation of (92), then essentially the same mixture of products (hexenones and ketene-derived products) should be formed on decomposition of the diazo ketones and on oxidation of the alkyne this was the case. 

In the presence of aprotonic organic solvents, both aromatic and aliphatic amines interact with 4-nitrophenyldiazonium in the same way. The first stage yields fast in corresponding triazenes. At the second stage, irrespective of initial amine nature, triazenes interact with an excess of diazo reagent and fonu l,3-bis(4-nitrophenyl)-triazene. Triazenes of aliphatic amines transform fast as well. In case of aromatic amines, the second stage yield depends on the inductive constants of substituents in an azo component. 

The time necessary for completion of the reaction may vary from 0.5 to 4 hours, depending on the actual activity of the alumina. The progress of conversion should be monitored by infrared analysis of a concentrated sample of the solution. Stirring should be continued for 15 minutes after the nitroso band at 1540 cm. has disappeared. A strong diazo band at about 2100 cm. will then be present. The carbonyl band at 1750 cm. initially due to nitrosocarbamate, will usually not disappear completely during the reaction, because some diethyl carbonate is formed in addition to carbon dioxide and ethanol. Diethyl carbonate is removed during the work-up procedure. 

Other electrophilic substitutions proceed with difficulty, or not at all. Nitrosation and diazo coupling require the presence of the strongly activating dimethylamino group (see Section VIII). Bromine adds, in the presence of sunlight, to give tetrabromotetrahydrobenzofuroxan (48) the initial attack is probably free-radical in nature. The product can be dehydrobrominated to form 4,7-, or a mixture of 4,5- and 4,6-dibromobenzofuroxan, depending upon the conditions. More conventional electrophilic bromination conditions have been tried in an attempt to obtain a monosubstituted product, but without success. 

Reaction of tosyl hydrazone 1 with a strong base initially leads to a diazo compound 3, which in some cases can be isolated ... 

Itishould be noticed that the similarity between the osmophore theory and Witt s chromophore colour theory does not extand much beyond the initial conception and there seems to be no connection between the odour and the colour of a body, it is indeed quite the exception for a body to have both a strong odour and a strong colour. Two prolific sources of colour, viz. the diazo group and a large molecule have no counterpart as regards odour, and it is probably only by chance that quinone and chroman both have pronounced odours and are the sources of colour. 

The strained bicyclic carbapenem framework of thienamycin is the host of three contiguous stereocenters and several heteroatoms (Scheme 1). Removal of the cysteamine side chain affixed to C-2 furnishes /J-keto ester 2 as a possible precursor. The intermolecular attack upon the keto function in 2 by a suitable thiol nucleophile could result in the formation of the natural product after dehydration of the initial tetrahedral adduct. In a most interesting and productive retrosynthetic maneuver, intermediate 2 could be traced in one step to a-diazo keto ester 4. It is important to recognize that diazo compounds, such as 4, are viable precursors to electron-deficient carbenes. In the synthetic direction, transition metal catalyzed decomposition of diazo keto ester 4 could conceivably furnish electron-deficient carbene 3 the intermediacy of 3 is expected to be brief, for it should readily insert into the proximal N-H bond to... 

The major problem of these diazotizations is oxidation of the initial aminophenols by nitrous acid to the corresponding quinones. Easily oxidized amines, in particular aminonaphthols, are therefore commonly diazotized in a weakly acidic medium (pH 3, so-called neutral diazotization) or in the presence of zinc or copper salts. This process, which is due to Sandmeyer, is important in the manufacture of diazo components for metal complex dyes, in particular those derived from l-amino-2-naphthol-4-sulfonic acid. Kozlov and Volodarskii (1969) measured the rates of diazotization of l-amino-2-naphthol-4-sulfonic acid in the presence of one equivalent of 13 different sulfates, chlorides, and nitrates of di- and trivalent metal ions (Cu2+, Sn2+, Zn2+, Mg2+, Fe2 +, Fe3+, Al3+, etc.). The rates are first-order with respect to the added salts. The highest rate is that in the presence of Cu2+. The anions also have a catalytic effect (CuCl2 > Cu(N03)2 > CuS04). The mechanistic basis of this metal ion catalysis is not yet clear. 

Broxton and Roper measured the rate of dissociation (A 3) of the (ii)-diazo ether, A 2, and the rate of the protection reaction (A p), i.e., the transformation of the (Z)-into the (ii)-ether ( protection because the diazo ether is protected against dediazoniation almost completely if present as the ( >isomer). Rate constants kx and k are known from Ritchie and Virtanen s work (1972). The results demonstrate firstly that the initial reaction of the diazonium ion takes place in such a way that almost exclusively the (Z)-ether is formed directly (ki/k3 = 120). The protection rate constant kp is a simple function of the intrinsic rate constants as shown in Scheme 6-4. 

An interesting rearrangement was found by Davies and Kirby (1967) in the diazo-tization of 7-amino-benzothiazole (6.68). As Scheme 6-45 shows, the diazonium ion formed initially rearranges under hydrolytic conditions into 7-amino-l,2,3-benzo-thiadiazole (6.69). 

Coming back to the chain reaction sequence (Scheme 8-50) the inclusion of the final step shown here demonstrates clearly that the initial formation of the aryl radical from the diazo ether (Scheme 8-49) may be only an initiation step. The arguments of Broxton concerning whether the homolytic dediazoniation starts with the diazo ether or with the diazonium ion therefore become irrelevant. 

In 1882 Griess discovered that in aqueous acidic solution 4-diazobenzenesulfonate and 4-methylaniline react quantitatively to yield 4-toluenediazonium ion and 4-ami-nobenzenesulfonic acid. This phenomenon is called diazo migration or diazo exchange. We now know that it is a consequence of the tautomerism of the initially formed l-(4 -methylphenyl)-3-(4 -sulfophenyl)-triazene, as discussed above. Griess also found another reaction that could not be explained at his time, but which is based on the tautomerism of intermediate triazenes occasionally, the reaction of an arenediazonium salt with a primary aromatic amine in weakly acidic solution yields a mixture of two isomeric aminoazo compounds (Scheme 13-21). 

Carbonyl oxides (formed by the reaction of diazo compounds with singlet oxygen) may also be used to oxidize sulphoxides74. The corresponding sulphone is formed in reasonable yields and the reaction may be carried out in the presence of the sulphide functionality. The reaction proceeds as shown in equation (21) and involves initial nucleophilic attack by the carbonyl oxide on the sulphoxide sulphur atom followed by the facile departure of the carbonyl compound yielding the required sulphone. 

The use of dirhodium(II) catalysts for catalytic reactions with diazo compounds was initiated by Ph. Teyssie [14] in the 1970s and rapidly spread to other laboratories [1]. The first uses were with dirhodium(II) tetraacetate and the more soluble tetraoctanoate, Rh2(oct)4 [15]. Rhodium acetate, revealed to have the paddle wheel structure and exist with a Rh-Rh single bond [16], was conve-... 

These tetrathiametallacyclohexanes are probably formed via the initial attack of diphenylcarbene, generated from the corresponding diazo compound, on a sulfur atom and subsequent ring expansion (Scheme 55). The... 

The diazo transfer reaction between p-toluenesulfonyl azide and active methylene compounds is a useful synthetic method for the preparation of a-diazo carbonyl compounds. However, the reaction of di-tert-butyl malonate and p-toluenesulfonyl azide to form di-tert-butyl diazomalonate proceeded to the extent of only 47% after 4 weeks with the usual procedure." The present procedure, which utilizes a two-phase medium and methyltri-n-octylammonium chloride (Aliquat 336) as phase-transfer catalyst, effects this same diazo transfer in 2 hours and has the additional advantage of avoiding the use of anhydrous solvents. This procedure has been employed for the preparation of diazoacetoacetates, diazoacetates, and diazomalonates (Table I). Ethyl and ten-butyl acetoacetate are converted to the corresponding a-diazoacetoacetates with saturated sodium carbonate as the aqueous phase. When aqueous sodium hydroxide is used with the acetoace-tates, the initially formed a-diazoacetoacetates undergo deacylation to the diazoacetates. Methyl esters are not suitable substrates, since they are too easily saponified under these conditions. 

---