Hydrazones diazo compounds

Oxidative Couplings of Heterocyclic Hydrazones. This method has opened the way to the preparation of azo derivatives of diazo compounds unobtainable by other means, ie, heterocycHc compounds ia which the diazotizable amino group is conjugated with the heterocycHc nitrogen atom as ia 2- and 4-amiQopyridine, compounds which do not normally yield stable diazonium salts (38). The reaction occurs as illustrated by equation 7 for the iateraction of (A/-methylcarbostyryl)hydrazone [28219-37-6] and dimethyl aniline the overall process is oxidation. 

A formal ring enlargement of diazirines to five-membered rings is also observed with some hydrazones of ketodiazirines (65CB2509). On attempted preparation of hydrazones (201) from ketodiazirine (200) at 0 C the diazo compounds (202) are plausible intermediates since their transformation to aminotriazoles (203) is known. 

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)... 

Thus it is not surprising that three-membered rings with two hetero atoms were mentioned in the literature at an early stage. For example, at the turn of the century, nitrones, hydrazones, and aliphatic diazo compounds were all formulated with three-membered rings (I, 2, 3). Later the three-membered ring structures for these compounds became questionable. The structure of the aliphatic diazo compounds was studied very intensively. For diazomethane no clas-... 

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

Such diazo compounds 3 however, that contain two electron-withdrawing substituents, are unstable under these reaction conditions. They further react by hydrolytic cleavage of one carbonyl substituent to give an anionic species 6, that is stabilized by resonance, and which yields the hydrazone 4 upon acidic workup ... 

When hydrazones are oxidized with HgO, Ag20, Mn02, lead tetraacetate, or certain other oxidizing agents, diazo compounds are obtained ... 

Diazo compounds can also be obtained by oxidation of the corresponding hydrazone,129 the route that is most common when one of the substituents is an aromatic ring. 

Lead tetraacetate, oxidation of a hydrazone to a diazo compound, 50, 7 Lithio ethyl acetate, 53, 67 Lithium, reductions in amine solvents, 50, 89 Lithium aluminum hydride, reduction of exo-3,4-dichloro-bicyclo-[3.2.l]oct-2-ene to 3-chlorobicyclo[3.2.l]oct-2-ene, 51, 61... 

The aliphatic diazo-compounds can also be prepared by careful dehydrogenation of the hydrazones (with HgO) (Curtius, Staudinger) and, conversely, they are converted into the latter by hydrogenation ... 

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. 

Non-functionalized aliphatic diazo compounds are fairly rare, and so are their reductions. Good examples of the reduction of diazo compounds to either amines or hydrazones are found with a-diazo ketones and a-diazo esters (pp. 124, 125, 160). 

In search of a convenient procedure for preparing diazo substrates for the cycloaddition to Cgg, Wudl introduced the base-induced decomposition of tosyl-hydrazones [116]. This procedure allows the in situ generation of the diazo compoimd without the requirement of its purification prior to addition to Cgg. Since they are rapidly trapped by the fullerene, even unstable diazo compounds can be successfully used in the 1,3-dipolar cycloaddition. In a one-pot reaction the tosyUiydrazone is converted into its anion with bases such as sodium methoxide or butylHfhium, which after decomposition readily adds to Cgg (at about 70 °C). This method was first proven to be successful with substrate 142. Some more reactions that indicate the versatility of this procedure are shown in Table 4.4. Reaction of 142 with CgQ under the previously described conditions and subsequent deprotection of the tert-butyl ester leads to [6,6]-phenyl-C5j-butyric acid (PCBA) that can easily be functionalized by esterification or amide-formation [116]. PCBA was used to obtain the already described binaphthyl-dimer (obtained from 149 by twofold addition) in a DCC-coupling reaction [122]. 

A -1,3,4-Thiadiazoline-1 -oxides (146) (Equation (18)) are formed by addition of diazo compounds (R2C=N2) to sulfines (R R C =S=0). The adducts from diazomethane and aryl substituted sulfines are unstable and give the thiadiazole (147) via a Pummerer-type aromatization <84CHEC-I(4)545>. The A -thiadiazoline-1,1-dioxide (149) has been produced by oxidation of the hydrazone (148) (Equation (19)) and treatment with sulfur dioxide <84CHEC-i(4)545>. 2-Alkylidenethiadiazolines can be obtained from the dipolar addition of diazo compounds to thioketenes <83CB66, 90TL3571, 92HCA1825>. 

Numerous methods to prepare individual classes of aliphatic diazo compounds have been extensively developed. The major strategies for their synthesis involve the alkaline cleavage of N-alkyl-N-nitroso-ureas, -carboxamides and -sulfonamides, dehydrogenation of hydrazones, as well as diazo group transfer from sulfonyl and related azides to active methylene compounds, and electrophilic diazoalkane substitution reactions. These synthetic methods have been comprehensively reviewed (15,16). Useful information on the preparation of selected diazo compounds can be found elsewhere (6,17). 

Stable representatives of telluroketones were not available until recently. 2,5-Dihydro-1,3,4-telluradiazole 172 can be prepared from hydrazones 171 and tellurium tetrachloride or tetrabromide in yields of 19-48 and 42-55%, respectively (Scheme 8.39) (237). Ketazines 173 were obtained as byproducts of this reaction in 32 5% yield. It was proposed that XeX4 is hrst reduced to TeX2 in the reaction medium. The latter species probably generates both the diazo compound and the telluroketone derived from hydrazone 3 and then a [3+2] cycloaddition occurs. In fact, both 172 and 173 were obtained when hydrazones 3a-c were treated with the difhcult-to-handle tellurium dichloride in the presence of triethylamine. 

Weiss and co-workersprepared a series of oxazohnylidene steroids 343 as luminescence dyes for application as potential intracellular diagnostic agents (Scheme 6.72). The key intermediate 2-aryl-5,5-dimethyl-4(57/)-thiooxazolones 341 were readily available from the corresponding 4(57/)-oxazolones 339. Reaction of 341 with 342, generated in situ from the hydrazone 340, gave 343 as expected. It was not possible to prepare 343 from 3-thio-androsta-l,4-dien-17-one since the requisite corresponding heterocyclic diazo compounds could not be prepared. 

Diazo compounds have previously been prepared by a variety of methods. Some of these methods Include hydrazone oxidations, the reaction of diazomethane with acid chlorides,4 the reaction of activated methylene compounds with tosyl azide, decomposition of N-nitroso compounds, ... 

Another method for the preparation of the 1,2,4,5-tetrazine system from a diazo compound was reported by Staudinger and Meyer (19HCA619). They reacted diaryldiazomethanes (321) with triethylphosphine and isolated the phosphazines (322). In moist benzene or chloroform these compounds were transformed into 3,3,6,6-tetraaryl-l,2,3,6-tetrahydro-1,2,4,5-tetrazines (323). This result was only obtained when triethylphosphine was used. The intermediate formation of hydrazones seems unlikely, since these compounds are stable and do not dimerize. A reaction which has a certain similarity to the above was reported by Merrill and Shechter (75TL4527). They obtained 3,6-diphenyl-l,4-dihydro-l,2,4,5-tetrazine (80) when the phosphazine (324) was hydrolyzed. 

Ketone hydrazones can be converted into aliphatic diazo compounds which are, in contrast to nonfluorinated analogs, quite stable at room temperature. 2-Diazo-l,l,1-trifluoropropane is obtained as a solution in diethyl ether or pentane by the oxidation of l,l,l-trifluoropropan-2-one hydrazone using silver oxide.243 Analogously, phenyl trifluoromethyl ketone hydrazone is oxidized to the diazo compound 6 by mercury(II) oxide in alkaline media.362 Bis(per-fluoromethyl)- 7 and bis(perfluoroethyl)diazomethane are prepared by lead(IV) acetate oxidation of the corresponding hydrazones in benzonitrile solution at 0-25 c.244,245... 

The development of modern organic pigments started with the synthesis of dyestuffs for the textile industry. The period up to 1900 was characterized by the discovery and development of many dyes derived from coal-tar intermediates. Rapid advances in color chemistry were initiated after the discovery of diazo compounds and azo derivatives (shown to be largely hydrazone derivatives). The wide color potential of this class of pigments and their relative ease of preparation led to the development of azo colors, which represent the largest fraction of manufactured organic pigments. 

A variation on the thermal reactions of diazo compounds with alkenes is the decomposition of salts of sulfonylhydrazones. This procedure, known as the BamfoTd-Stevens reaction, is believed to occur via the formation of diazo compounds. Subsequent 1,2-hydrogen shifts generally lead to the formation of alkenes as the final products. Cyclopropanes may also be formed as the result of intramolecular 1,3-C—H insertion reactions or when the original hydrazone substrate contains a remote alkenic group as a site for intramolecular cyclopropanation.10... 

Acylation of 2- -octylthiochroman by AczO is quantitative at the 6-position (Equation 23) <2003PS(178)993> and benzoylation of thioxanthene occurs at the 2- and 7-positions and both ketone functions have been converted into the hydrazones and thence the diazo compound 277. The bis-carbene derived from 277 by cryogenic photolysis has been used to study magnetic coupling interactions through the sulfur atom (Scheme 32) <1997JA8058>. 

Like aryl azides, diazo compounds are susceptible to reduction by thiols and a study of the diazotrifluoropropionyl group has been made by Taka-gaki et al. (1980) who showed that the corresponding hydrazone is formed (Fig. 3.6). For example, one reagent 20 pM) was converted to the extent of 24% in 3 h at room temperature by 30 mM cysteine, at pH 8.0. 

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