Rearrangement diazo compounds

This synthetic appproach has been used in a few cases for the preparation of pyridazines from diazo compounds and cyclopropenes. In general, cycloadducts (176) are formed first and these rearrange in the presence of acid or alkali to pyridazines (Scheme 98) (69TL2659, 76H(5)40l). Tetrachlorocyclopropene reacts similarly and it was found that the stability of the bicyclic intermediates is mainly dependent on substitution (78JCR(S)40, 78JCR(M)0582>. 

Methylvinyldiazirine (199) rearranges at room temperature in the course of some days. Formation of the linear isomer is followed by electrocyclic ring closure to give 3-methyl-pyrazole. The linear diazo compound could be trapped by its reaction with acids to form esters, while the starting diazirine (199) is inert towards acids (B-71MI50801). 

Cyclization of the diazo compound (108) with a copper catalyst affords the clavulanic acid derivatives (110) and (111), possibly via rearrangement of the sulfur ylide (109) (80H(14)1999). Similar reactions have been reported in the recent literature (80H(14)1967, 81H(16)1305, 80TL31). 

The Bamford-Stevens decomposition of tosylhydrazones by base has been applied to steroids, although not extensively. It has been demonstrated that the reaction proceeds via a diazo compound which undergoes rapid decomposition. The course of this decomposition depends upon the conditions in proton-donating solvents the reaction has the characteristics of a process involving carbonium ions, and olefins are formed, often accompanied by Wagner-Meerwein-type rearrangement. In aprotic solvents the diazo compound appears to give carbene intermediates which form olefins and insertion products ... 

Hexafluoroacetone azine accepts nucleophiles (ROH, RSH, R NH) in positions 1 and 2 to yield hydrazones [27] Phosphites give open-chain products via a skeletal rearrangement [22] Radical addition reactions are also reported [22] Treatment of tnfluoropyruvates with tosylhydrazine and phosphorus oxychlo-ride-pyndme yields tnfluoromethyl-substituted diazo compounds [24] (equation 3)... 

In this review an attempt is made to discuss all the important interactions of highly reactive divalent carbon derivatives (carbenes, methylenes) and heterocyclic compounds and the accompanying molecular rearrangements. The most widely studied reactions have been those of dihalocarbenes, particularly dichlorocarbene, and the a-ketocarbenes obtained by photolytic or copper-catalyzed decomposition of diazo compounds such as diazoacetic ester or diazoacetone. The reactions of diazomethane with heterocyclic compounds have already been reviewed in this series. ... 

The synthesis of thiepins 14 was unsuccessful in the case of R1 = i-Pr,79 but if the substituents in the ortho positions to sulfur arc /erf-butyl, then thiepin 14 (R1 = t-Bu R2 = Me) can be isolated in 99% yield.80 Rearrangement of diazo compound 13 (R1 = t-Bu R2 = H), which does not contain the methyl group in position 4, catalyzed by dimeric ( y3-allyl)chloropalladium gives, however, the corresponding e.w-methylene compound. The thiepin 14 (R1 = t-Bu, R2 = H) can be obtained in low yield (13 %) by treatment of the diazo compound with anhydrous hydrogen chloride in diethyl ether at — 20 C.13 In contrast, the ethyl thiepin-3,5-or -4,5-dicarboxylates can be prepared by the palladium catalysis method in satisfying yields.81... 

In the case of sodium 2-(diarylmethylene)cyclopentanone tosylhydrazones 3, however, thermolysis gives the 3//-1,2-benzodiazepines 6 in good yield selected examples are shown. It is suggested that steric constraints in the diazo compounds 4 favor the [1,7] ring closure. The reaction proceeds by way of the intermediates 5, which rearrange to the products by a [1,5] shift of hydrogen.115... 

Cyclizations of doubly unsaturated diazo compounds containing a thiophene ring within rather than at the end of the diene system to yield thicnodiazepines have also been reported. Thus, thermolysis of the sodium salt 7 gives the l//-thieno[3,2-r/]-2,3-diazepine 9. The intermediate 8 rearranges to the more stable product 9 by a symmetry allowed [1,5] shift of hydrogen.14,1... 

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). 

The arenediazocyanides have been known since 1879. They played an important role in the Hantzsch-Bamberger debate on the (Z)/( ,)-isomerism of diazo compounds (see Sec. 7.1). When an aqueous solution of a diazonium salt is added to a solution of sodium or potassium cyanide, both in relatively high concentration, at a temperature below 0°C, a yellow to red (Z)-arenediazocyanide starts to crystallize. Hantzsch and Schulze (1895 a) found that these compounds rearrange into the (ii)-isomers, which have a bathochromically shifted visible absorption (see Sec. 7.1). Under strongly alkaline conditions a 1 2 adduct is formed, to which Stephenson and Waters (1939) assigned the structure 6.36. It was never corroborated, however, by modern instrumental analysis. 

In this section we first discuss photolytic reactions of arenediazonium salts and report on quinone diazides at the end of the section in the context of imaging technology. Diazoalkenes, non-quinonoid diazo ketones, and the Wolff rearrangement are treated in the book on aliphatic diazo compounds (Zollinger, 1995, Chap. 8). 

Oxo-2,5-cyclohexadienylidene [83] was generated in solid argon at 9 K by irradiation of diazo compound [84] with visible light (A>495 nm) (Sander et al., 1988 Bucher and Sander, 1992 Bucher et al., 1992). The IR, UV, and esr spectra of [83] were in accord with a structure having a triplet state with one delocalized electron. In the IR spectrum of the carbene [83] the r (CO) mode was found at 1496 cm which indicates a bond order of the C—O bond considerably less than 2. The low-temperature reaction of carbene [83] with CO generated the keto-ketene [85]. Irradiation (A = 543 10 nm) of [83] led to its transformation into a very labile species, presumed to be [86], which rearranged back to [83] not only under UV or... 

Thermolysis of 58a in butanol affords, together with 17% of 60a (R = C4H9) which evidences the intermediacy of the thiophosphene 59 a, a variety of partly atypical products which seriously impede the desired rearrangement38. Photolysis of 58b in methanol is also found to give only 18 % 1,2-P/C shift to form the heterocumulene 59b, from which the thiophosphinic rater 60b (R = CH3) results 39). As already mentioned in connection with the photolysis of diazo compounds of type 36 (see Sect. 2.2), Wolff rearrangement (9%) and O/H insertion (6%) once again compete with thiophosphinic ester formation. Moreover, solvolysis of the P(S)/C(N2) bond 391 prevents a greater contribution of carbene products to the overall yield. 

The Davies group has described several examples of a rhodium-catalyzed decomposition of a diazo-compound followed by a [2+1] cycloaddition to give divinyl cyclopropanes, which then can undergo a Cope rearrangement. Reaction of the pyrrol derivative 6/2-51 and the diazo compound 6/2-52 led to the tropane nucleus 6/2-54 via the cyclopropane derivative 6/2-53 (Scheme 6/2.11) [201]. Using (S)-lactate and (R)-pari lolaclorie as chiral auxiliaries at the diazo compound, a diastereoselectivity of around 90 10 could be achieved in both cases. 

Protected 6-amino-hexahydro-l,7-dioxopyrazolo[l,2-4]pyrazole-2-carboxylic acid 274 is available by a thermolytic decomposition of diazo compound 273 via the Wolff rearrangement. The starting compound is simply available by alkylation of racemic 272 with the corresponding bromoacetoacetate and subsequent diazo transfer reaction (Scheme 35) <1996TL4891>. 

Table 23. Rearrangements upon catalytic decomposition of diazo compounds... 

Enol ether additives were used to probe the protonation of 3-cyclopen-tenylidene (127). Treatment of A-nitroso-A-(2-vinylcyclopropyl)urea (124) with sodium methoxide generates 2-vinylcyclopropylidene (126) by way of the labile diazo compound 125 (Scheme 25). For simplicity, products derived directly from 126 (allene, ether, cycloadduct) are not shown in Scheme 25. The Skat-tebpl rearrangement of 126 generates 127 whose protonation leads to the 3-cyclopentenyl cation (128). In the presence of methanol, cyclopentadiene (130) and 3-methoxycyclopentene (132) were obtained.53 With an equimolar mixture of methyl vinyl ether and methanol, cycloaddition of 127 (—> 131)... 

The second intermediate s identity has been debated since the mid-1980s. In 1984, Liu and Tomioka suggested that it was a carbene-alkenc complex (CAC).17 Similar complexes had been previously postulated to rationalize the negative activation energies observed in certain carbene-alkene addition reactions.11,30 A second intermediate is not limited to the CAC, however. In fact any other intermediate, in addition to the carbene, will satisfy the kinetic observations i.e., that a correlation of addn/rearr vs. [alkene] is curved, whereas the double reciprocal plot is linear.31 Proposed second intermediates include the CAC,17 an excited carbene,31 a diazo compound,23 or an excited diazirine.22,26 We will consider the last three proposals collectively below as rearrangements in the excited state (RIES). 

Cyclohexadienylidenes, disubstituted at the 4-position are expected to be kinetically more stable than the parent carbene, however, the rearrangement to benzene derivatives is still very exothermic. The gas phase chemistry of 4,4-dimethyl-2,5-cyclohexadienylidene Is was investigated by Jones et al.100,101 The gas phase pyrolysis of the diazo compound 2s produces a mixture of p-xylene and toluene, and by crossover experiments it was demonstrated that the methyl group transfer occurs intermolecularly via free radicals. Thus, the pyrolysis of a mixture of the dimethyl and the diethyl derivative 2s and 2t... 

The use of copper as a catalyst in carbenoid transfer has its roots in the Amdt-Eistert reaction, Eq. 1 (3). Although the original 1935 paper describes the Wolff rearrangement of a-diazo ketones to homologous carboxylic acids using silver, the authors mention that copper may be substituted in this reaction. In 1952, Yates (4) demonstrated that copper bronze induces insertion of diazo compounds into the X-H bond of alcohols, amines, and phenols without rearrangement, Eq. 2. Yates proposal of a distinct metal carbenoid intermediate formed the basis of the currently accepted mechanistic construct for the cyclopropanation reaction using diazo compounds. 

The unexpected feature of the reaction of the primary aromatic amines with nitrous acid is that the diazo-compound, which is doubtless formed at low temperatures according to the scheme so far used, undergoes rearrangement by the acid present in the solution, and forms... 

The mechanism of the coupling reaction has been very exhaustively studied. Summarising first what has already been mentioned, it must be noted that the reaction is not confined to the aromatic series, for diazo-compounds condense also with enols and with the very closely related aliphatic aci-nitro-compounds. The final products of these reactions are not azo-compounds, but the isomeric hydrazones formed from them by rearrangement. 

This is the first example of a direct coupling of a diazo compound in a / position of the thiophene nucleus. The Beckmann rearrangement with the ketoxime of 2-thienylketone was found to give poor yields of the aceto-2-thiopheneamide. Furthermore, the Schmidt reaction using hydrazoic and sulphuric acids was investigated and did give rise to aceto-2-thiopheneamide but probably as an eutectic with the isomeric 2-thenoylmethylamide. 

---