Diazopropane

4- diene has also been prepared by oxidation of cycloocta-tetraene with lead tetraacetate,5 and by chlorination of cyclo-octatetraene with sulfuryl chloride followed by displacement with potassium acetate.3,7 The two other geometric isomers of the diene have been prepared by another method.6 trans,trans, 

4- Diacetoxy-1,3-butadiene is a reactive diene in the Diels-Alder reaction. It has been used as the starting material in stereospecific syntheses of conduritol-D8 and shikimic acid,9,10 and in a simple general method of preparation of benzene derivatives, especially unsymmetrical biphenyls.11,12 

Frick Chemical Laboratory, Princeton University, Princeton, New Jersey. 

Caution 2-Diazopropane is volatile and presumably toxic. All operations should be carried out in an efficient hood behind a protective screen. 

British Drug Houses Laboratory Reagent yellow mercuric oxide was used for most runs. The preparation was not apparently improved by the use of freshly precipitated mercuric oxide. 

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The dipolar cycloaddition of 2-diazopropane to l-methyl-3-phenylpyridazin-6(l//)-one takes place through an unstable adduct which thermally decomposes to a 1,2-diazepinone, a pyridazinone and diazanorcaradiene derivative (Scheme 46). 

In the case of the reaction between 2-diazopropane and diphenyldiacetylene, the reverse (as compared with other diynes) orientation of addition of the first molecule of the diazo compound with a predominant formation of 4-phenylethynylpyrazole is observed. Therefore, it is noteworthy that whereas the regioselectivity of the addition of diazoalkanes to alkenes is well studied audits products have, as a rule, the structure been predicted with respect to electron effects, the problem of orientation... 

Dipolar addition of 2-diazopropane to diacetylene in EtaO at -25°C to give 3,3-dimethyl-5-ethynylpyrazole (83) (42% yield) and at 0°C to give dipyrazole 84 (60% yield) has been described (83TL1775). 

Dipolar cycloaddition of 2-diazopropane and 1,3-diphenyldinitrilimine to E- and Z-methoxybutenynes occurs at the triple bond to form 3,3-dimethyl-5-(2-methoxyvinyl)pyrazole (168) and a mixture of , Z-l,3-diphenyl-4- (169) and -5-(2-methoxyvinyl)pyrazole (170) [70CR(C)80]. 

The ring-opening process leading to 164 (route a) is analogous to that which has been demonstrated to follow the cycloadditions of tosyl azide to certain enamines . Similar results have been reported for the reaction of 2,3-diphenylcyclopropenone with 2-diazopropane . Other 1,3-dipolar cycloadditions with thiirene dioxides could also be affected (see below). 

The 2-diazopropane 59 reacts at 0 °C in dichloromethane with the imidate 60a to give exclusively the adduct 61a after 10 h of reaction. This compound results from the regioselective 1,3-dipolar cycloaddition of the 2-diazopropane to the imidate C - N bond (Scheme 13). 

Under similar conditions, reaction of imidate 60b with 2-diazopropane performed at 0 °C in dichloromethane, was completed in less than 10 h and gave mainly product 61b. As before, the structure of 61b was determined via a detailed mono- and bidimensional NMR study. 

These results show for the first time, the reactivity of the double bond C = N with the 2 diazopropane that constitutes an efficient route for the preparation of new heterocyclic systems. In all cases, the reaction is peris-elective only the double bond C = N is affected diazo carbon attacks the quaternary carbon of the imidate 60 and not the double bond C = O (substrates 60b and 60c). Indeed, diazopropane reacts with ketones with inverse regioselectivity (with regards to imidates 60) to yield oxadiazoUnes [32,33] (Scheme 14). 

In conclusion, we have been successful in developing a new method for the synthesis of [ 1,2,3]-triazoles by regioselective 1,3-dipolar cycloaddition of 2-diazopropane with imidates 60 in good yields. 

We now report the synthesis of new antibacterial 3H-pyrazoles by regioselective 1,3-dipolar cycloaddition of the versatile 2-diazopropane to nonprotected disubstituted propargyl alcohols and that the unsubstituted propar-gyl alcohol allows the double addition of 2-diazopropane and gives a 3H-pyrazole with formal insertion of the dimethylcarbene into a carbon-carbon bond. We also show that the photolysis of the 3H-pyrazoles leads to new alcohols containing the cyclopropenyl unit. 

Whereas the Rh2(OAc)4-catalyzed addition of diazoalkanes to propargyl alcohols readily gives the insertion of the carbene into the 0-H bond, with only a small amoimt of cyclopropenation of the resulting propargylic ether [54] the 2-diazopropane 59 reacts at 0 °C with l,l-diphenyl-2-propyn-l-ol 62a in dichloromethane and exclusively gives, after 10 h of reaction, only the adduct 63a isolated in 75% yield and corresponding to the regioselective 1,3-dipolar cycloaddition of the 2-diazopropane to the alkyne C - C bond (Scheme 15). 

Analogously, the 1,3-dipolar cycloaddition reaction of 2-diazopropane with propargyl alcohol 62b, performed at 0 °C in dichloromethane, was completed in less then 10 h and led to a monoadduct 63b with the same regioselective addition mode of 59 to the triple bond. The HMBC spectrum showed correlations between the ethylenic proton and the carbons C3 and C5 and between the methyl protons and the carbons C3 and C4. 

It is noteworthy that the addition of an excess of the 2-diazopropane to the alkynes 62a,b did not give the corresponding bisadduct of diazoalkane. It... 

This study demonstrates that the addition of the 2-diazopropane with the triple bond of propargyl alcohols is regioselective, and affords new antibacterial 3H-pyrazoles. The photochemical reaction of these 3H-pyrazoles selectively leads to a- and 6-hydroxy cyclopropenes. The overall transformation constitutes a simple straightforward route to substituted cyclopropenyl alcohols without initial protection of the propargyl alcohol hydroxyl group. 

Some examples of carbene dimer formation resulting from diazoalkane decomposition on transition-metal surfaces have been reported. Diazomethane is decomposed to give ethylene and N2 upon passage over a C0O/M0O3 catalyst as well as on Ni, Pd, Fe, Co, Ru and Cu surfaces 367). Similarly, 2-diazopropane is readily decomposed on Raney nickel 368). At room temperature, propene and N2 were the only detectable products, but above 50 °C, the carbene dimer 2,3-dimethyl-2-butene started to appear which reached its maximum yield at 100 °C, where approximately 40 % of the carbene fragments dimerized. It is assumed 367,368), that surface carbenes are formed as intermediates from both diazomethane and 2-diazopropane which either dimerize or desorb by migration of a P-hydrogren, if available (Scheme 40). 

The 1,3-dipolar cycloaddition of diazomethane to MFA (24) occurred exclusively at the C2-C3 Jt-bond to give 4-(fluoromethylene)pyrazolines. The methylene group of diazomethane was regioselectively attached to the C2 carbon atom of 24 with a syw.anti ratio of 88 12 [72b], DFA (25) similarly reacted with diazomethane to give 4-(difluoromethylene)pyrazoline 89 selectively [72b, 86], The cycloaddition reaction of bulkier 2-diazopropane with DFA was less regioselective. 

Ultraviolet irradiation of oxadiazoline (38d) at 333.6 nm (or irradiation using benzophenone as a triplet sensitiser) gave 2-diazopropane and methyl acetate. A triplet biradical intermediate formed by cleavage of the C(OMe)—N bond was postulated <90TL863>. Oxadiazolinone (42) underwent nucleophilic attack at the carbonyl group by methyllithium to give acetate (41) after treatment of the product with acetyl chloride <89CJC1753>. 

On the other hand, the analogous reaction of 2,2,4,4-tetramethyl-3-thioxocyclo-butanone and 2-diazopropane afforded a stable cycloadduct, which upon heating eliminated N2 and yielded a mixture of thiirane (46) and vinyl thioether 47 (85). A similar competition involving both an electrocyclization and a 1,4-H shift was observed in the case of diisopropylthioketone (5)-methylide (39). 

Not unexpectedly, predictions on reactivity and regiochemistry based on a FMO treatment can be overruled by steric effects (13). The change in reactivity may be illustrated by the following example 2-Phenylsulfonyl-norbomadiene reacts with 2-diazopropane at the electron-deficient C=C bond, as expected. However, 2-phenylsulfonyl-3-trimethylsilyl-norbomadiene reacts with the same dipole at the unsubstituted double bond, probably as a result of the steric bulk of the trimethylsilyl group (27). 

An interesting preparation of aliphatic diazoalkanes (R R C = N2 R, R = alkyl) involves the photolysis of 2-alkoxy-2,5-dihydro-1,3.4-oxadiazoles (see Scheme 8.49). When the photolysis is carried out in the presence of an appropriate dipolarophUe, the diazo compounds can be intercepted (prior to their further photolysis) by a [3 + 2] cycloaddition reaction (54). As an example, 2-diazopropane was intercepted with A-phenylmaleimide (54) and norbornenes (55) to give the corresponding A -pyrazolines. 

Stanovnik and co-workers (100,101) systematically investigated the cycloaddition reactions of diazoalkanes with unsaturated nitrogen heterocycles, such as azolo-[l,5-fl]pyridines, pyridazin-3(2/7)-ones, and [fo]-fused azolo- and azinopyridazines. The Stanovnik group have studied the further transformations of the products and reviews of this chemistry are available. In a typical example, the reaction of 6-chlorotetrazolo[l,5-/7]pyridazine (37) with 2-diazopropane yields the NH,NH-dihy-dro-pyrazolo[4,3-(i]tetrazolo[l,5-/7]pyridazine 38 (102) (Scheme 8.11). The latter substrate reacts with acetone to produce an azomethine imine 39 that thermally rearranges to give the fused dihydro-1,2-diazepine 40. The azomethine imine obtained with glucose can be trapped with methyl acrylate to furnish the C-nucleoside 41 (103). 

With 2-diazopropane, two stereoisomers of the resulting tricyclic product 116 (cis, anti, cis and cis, syn, cis) were obtained (183). Formation of 116 can be rationalized by N2 extrusion from the cycloaddition product 114 and a subsequent [34 + 22 ] cycloaddition of the resulting 3-alkylidene-l,2,3-diazaphosphole 115 with the remaining heterophosphole 110. When an excess of 2-diazopropane was used, 115 was trapped by 1,3-dipolar cycloaddition across the exocyclic P=C bond. 

The electron-deficient C —C double bond of dimethyl trieyclo[4.2.1.02S]nona-3,7-diene-3,4-dicarboxylate readily reacted with 2-diazopropane to give the [3 + 2] cycloadduct dimethyl 6,6-dimethyl-4,5-diazatricyclo[7.2.1,02 8]dodeca-4,10-diene-3,7-dicarboxylate (21b) by attack at the a-face.27 Similar reaction of the tricyclic ester with diazomethane gave dimethyl 4,5-di-azatricyclo[7.2.1.02-8]dodeca-4,10-diene-3,7-dicarboxylate (21a).28... 

Diazopropane (called 2-Diazo-propan or Dimethyldiazomethan in Ger), (C CrN/N, mobile red liq of unpleasant, overpowering odor, bp --31.2° at 14mm press dec at RT with evolution of heat loss of N may de-flgr suddenly reacts violently with acids (Refs 2 3)... 

The most commonly used diazoalkanes have been diphenyldiazomethane (DPD) and 2-diazopropane (DAP), on account of their ready accessibility. The numerous other examples include l-phenyldiazoethanet0,t ... 

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