Secondary diazo compounds

The main product of the acid catalyzed hydrolysis of benzoylphenyl-diazomethane in dioxane—water is benzoine which has been isolated with 88 % yield [220], viz. 

A small part of the primary product rearranges to form diphenylacetic acid. The reaction rate is proportional to the product of concentrations of substrate and H30+, and the solvent isotope effect (kH/kD ) is larger than 1 (Table 19) [220, 221]. General catalysis by chloroacetic acid has been observed [220]. The reaction rate is increased by electron-releasing substituents and decreased by electron-withdrawing substituents at the aromatic ring. The data follow Hammett s rule with a p value of —2.38 [221]. There is no doubt that the reaction takes place with ratedetermining proton transfer in the first step (A-SE2 mechanism). The same conclusion may be drawn on the basis of similar evidence for the acid catalyzed hydrolysis of 2-diazoacenaphthenone [222]. 

These findings are not surprising since the alpha carbon atoms of these diazo compounds carry an aromatic ring. However, it has been observed recently by Dahn et al. [210] that solvent isotope effects are larger than 1 in the acid catalyzed hydrolyses of various secondary diazoketones (such as 3-diazo-2-butanone), ethyl a-diazopropionate, and l,l,l-trifluoro-2-diazopropane. Similar results have been obtained by Jugelt and Berseck 

3- diazo-2-butanone in dichloroacetate buffers [223] and the hydrolysis of 1-benzoyl-l-diazoethane in chloroacetate buffers [224]. It appears that proton transfer is rate-determining in these examples because the diazo group is bonded to a secondary carbon. 

Similar conclusions may be drawn from a discussion of the reaction products. As the product ratios do not depend on [H30+], it is likely that all products are formed via a common intermediate. It is significant that alkenes are among the products of hydrolysis of 3-diazo-2-butanone and 

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The hydrofluoride anion is also useful for substituting tertiary diazo groups by hydrogen fluoride under phase-transfer conditions, giving products 4. The reaction is less efficient on secondary diazo compounds.330... 

Evidence for rate-determining proton transfer (kH/ku > 1, Table 19) has been obtained also for the hydrolyses of the unusual secondary diazo compounds (EtO)2 PO C(N2 )C6H5 and (C6H5 )2PO C(N2 )C6HS [226]. All results of Hammett p values in the hydrolysis of diazo compounds are collected in Table 20. The first three entries refer to the A2 mechanism, the other ones to the A-SE 2 mechanism. 

A 1,3-dipolar cycloaddition of ethyl propiolate and ethyl diazoacetate was catalyzed by InCb in water to afford pyrazole bis-ester. For secondary diazo compounds, the InCU-catalyzed 1,3-dipolar cycloaddition often gives a mixture of two regioisomers. 

The 1,3-dipolar addition of secondary diazo-compounds to 1,3,3-trimethylcyclo-propene affords 2,3-diazabicyclo[3,l,0]hex-3-enes [cf. (130)], but with diazoacetic ester this product, with an acidic proton at C-4, undergoes rearrangement to ethyl 3,4,4-trimethyl-l,4-dihydropyridazine-6-carboxylate. Further additions of phenyl azide to methylenecyclopropanes have shown that the presence of a carboxylate group in the three-membered ring causes the initially formed spirodihydrotriazole to undergo rearrangement to a 4-substituted 1,2,3-triazole. ... 

The photolysis of chlorodiazirine was investigated in several cases. From chloromethyl-diazirine (232) vinyl chloride was formed as the stable primary product of stabilization of chloromethylcarbene, with acetylene and hydrogen chloride as secondary products. Some 1,1-dichloroethane was assumed to have been formed through a linear diazo compound by reaction with HCl. Added HBr yielded 1-bromo-l-chloroethane (76MI5Q800). 

Research into the mechanism of diazotization was based on Bamberger s supposition (1894 b) that the reaction corresponds to the formation of A-nitroso-A-alkyl-arylamines. The TV-nitrosation of secondary amines finishes at the nitrosoamine stage (because protolysis is not possible), but primary nitrosoamines are quickly transformed into diazo compounds in a moderately to strongly acidic medium. The process probably takes place by a prototropic rearrangement to the diazohydroxide, which is then attacked by a hydroxonium ion to yield the diazonium salt (Scheme 3-1 see also Sec. 3.4). 

In the historical introduction to this book (Sec. 1.1) it was mentioned that the discoverer of diazo compounds, Peter Griess, realized quite early (1864 a) that these species could react with alkali hydroxides. Thirty years later Schraube and Schmidt (1894) found that the primary product from the addition of a hydroxide ion to a diazo compound can isomerize to form a secondary product. In this section we will discuss the equilibria of the first acid-base process of aromatic diazonium ions. In the following section additional acid-base reactions will be treated in connection with the isomerism of addition products of hydroxide ions to diazonium ions. 

The reaction of diazo compounds with amines is similar to 10-15. The acidity of amines is not great enough for the reaction to proceed without a catalyst, but BF3, which converts the amine to the F3B-NHR2 complex, enables the reaction to take place. Cuprous cyanide can also be used as a catalyst. The most common substrate is diazomethane, in which case this is a method for the methylation of amines. Ammonia has been used as the amine but, as in the case of 10-44, mixtures of primary, secondary, and tertiary amines are obtained. Primary aliphatic amines give mixtures of secondary and tertiary amines. Secondary amines give successful alkylation. Primary aromatic amines also give the reaction, but diaryl or arylalkyl-amines react very poorly. 

Amides can also be alkylated with diazo compounds, as in 10-49. Salts of sulfonamides (ArS02NH ) can be used to attack alkyl halides to prepare N-alkyl sulfonamides (ArS02NHR) that can be further alkylated to ArS02NRR. Hydrolysis of the latter is a good method for the preparation of secondary amines. Secondary amines can also be made by crown ether assisted alkylation of F3CCONHR (R = alkyl or aryl) and hydrolysis of the resulting F3CCONRR. ... 

Insertion of a carbene unit into the N—H bond of primary or secondary amines by copper salt catalyzed decomposition of diazo compounds has been known for a number of years14). The copper chelate promoted reaction of diazodiphenyl-methane 291) or 2-diazo-1,2-diphenyl-1-ethanone 292) with primary benzylamines or... 

Deuterium kinetic isotope effects, secondary, and transition state structure, 31,143 Diazo compounds, aliphatic, reactions with acids, 5, 331... 

The IR spectrum which can be measured in argon at 10 K after irradiation of diazo compound 18 with k = 313 nm is relatively complex. But the absorptions of 19 can be extracted by a subsequent irradiation with k > 570 nm. The signals of 19 decrease in intensity during this secondary irradiation. They fit much better with the bands calculated for T-19 than for S-19. The product formed under these conditions (X > 570 nm) is the ring-opened carbene 16, which in this case can directly be detected and shows an IR spectrum which is in agreement with that of S-16. Intermediate 16 can be transferred photochemically to 2-cyano-2/7-azirene (17) with X > 313 nm, which is the main product in the primary irradiation of diazocompound 18 with this wavelength. 

Superior passive stabilised diazo compounds are afforded by the diazoamino compounds (triazenes) that arise by reaction of diazonium salts with a variety of secondary amines [114]. Typically, sarcosine (CH3NHCH2COOH), which gives products based on structure 4.114, as well as N-methyltaurine (CH3NHCH2CH2SO3H) and N methylaniline-4 Sulphonic acid,... 

Laser flash photolysis of phenylchlorodiazirine was used to measure the absolute rate constants for intermolecular insertion of phenylchlorocarbene into CH bonds of a variety of co-reactants. Selective stabilization of the carbene ground state by r-complexation to benzene was proposed to explain the slower insertions observed in this solvent in comparison with those in pentane. Insertion into the secondary CH bond of cyclohexane showed a primary kinetic isotope effect k ikY) of 3.8. l-Hydroxymethyl-9-fluorenylidene (79), generated by photolysis of the corresponding diazo compound, gave aldehyde (80) in benzene or acetonitrile via intramolecular H-transfer. In methanol, the major product was the ether, formed by insertion of the carbene into the MeO-H bond, and the aldehyde (80) was formed in minor amounts through H-transfer from the triplet carbene to give a triplet diradical which can relax to the enol. 

A Sandmeyer reaction leading to the 3-chloro derivatives was observed upon treatment of 3-diazotriazoles with aqueous hydrochloric acid [1898LA33 26JCS1729 78ZN(B)216]. 3-Diazotriazole was reduced to the parent triazole by treatment at 0°C with primary and secondary alcohols [86DIS(B) (46) 3052]. The mechanism is not clear, but the process may be envisaged as involving hydride transfer from the intermediate 244 obtained by nucleophilic addition of alcohols to the diazo compound (Scheme 70). 

The second class of benzo-fused heterocycles accessible from benzofuroxans are benzimidazole oxides. In this case only one carbon from the co-reactant is incorporated in the product. With primary nitroalkanes 2-substituted l-hydroxybenzimidazole-3-oxides (46) are formed via displacement of nitrite, and / -sulfones behave similarly. The nitrile group of a-cyanoacetamides is likewise eliminated to alford 2-amide derivatives (46 R = CONRjX and the corresponding esters are formed in addition to the expected quinoxaline dioxides from acetoacetate esters. Under similar conditions secondary nitroalkyl compounds afford 2,2-disubstituted 2//-benzimidazole-1,3-dioxides (47). Benzimidazoles can also result from reaction of benzofuroxans with phosphorus ylides <86T3631>, nitrones (85H(23)1625>, and diazo compounds <75TL3577>. 

A neutral diazo compound can be considered as both a nucleophile and an electrophile. Thus, it can be substituted by the combination of an electrophilic moiety and a nucleophilic moiety (X+ Nu ") (Scheme 8). In practice, the diazomethyl group is transformed to the fluoromethyl group by treatment with hydrogen fluoride/pyridine mixture (70 30 w/w) (X = H Nu = F), or to the halofluoromethyl group by addition of A-halosuccinimide in the same medium (X = Cl, Br, I Nu = F), e.g. formation of l.16 The reaction can be performed on secondary diazo alkanes, diazo ketones or diazo esters.16 90 316... 

Aviv and Gross developed an interesting insertion reaction of diazo compounds into a secondary amine-hydrogen bond in the presence of Fe-corrole complexes (Scheme 7.8) [12], Competition experiments performed in the presence of an amine and an alkene revealed the N—H-insertion reaction to be much faster than the cyclopropanation of the C=C bond. Apart from this chemoselectivity issue, the reactions are characterized by their very short reaction times most insertion reactions were completed within 1 min at room temperature. Most recently, Woo s group reported on a similar process using commercially available iron tetraphenyl-porphyrin [Fe(TPP)] dichloride [13]. 

An attractive alternative to the direct preparation of enamines from mono-substituted phosphonate reagents is the use of dimethyl diazomethylphosphonate (Me0)2P(0)CH= N2. Treatment of this diazo compound with t-BuOK (or with LiOH or K2C03), followed by various ketones in the presence of secondary amines, delivered the corresponding enamines251-253 (equation 17). In the presence of amines, (MeO)2P(0)CH= N2 and RCHO afforded the terminal acetylenes RC=CH. 

Coupling reactions with diazo compounds which are very sensitive to alkali often are most successful when pyridine is used as an acidfixing agent. This is especially true in the preparation of secondary polyazo dyes with l-amino-2-naphthol ethers or their sulfonic acids as intermediates. ... 

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