Tosyl azide azides

Recendy, Guiver et al. reported a number of derivatives of polysulfone and poly(aryl sulfone).172 188 Polysulfones were activated either on the ortho-sulfone sites or the ortho-ether sites by direct lithiation or bromination-lithiation. The lithiated intermediates were claimed to be quantitatively converted to azides by treatment with tosyl azides. Azides are thermally and photochemically labile groups capable of being transformed readily into a number of other useful derivatives. 

Tosyl azide reacts differently to give sulfonamide derivatives 134). The morpholine enamine from dibenzylketone (196) for instance reacted with tosylazide to give 197 and phenyldiazomethane (198), which was trapped with acetic acid giving benzyl acetate 134). 

Intermediate 37 can be transformed into ( )-thienamycin [( )-1)] through a sequence of reactions nearly identical to that presented in Scheme 3 (see 22— 1). Thus, exposure of /(-keto ester 37 to tosyl azide and triethylamine results in the facile formation of pure, crystalline diazo keto ester 4 in 65 % yield from 36 (see Scheme 5). Rhodium(n) acetate catalyzed decomposition of 4, followed by intramolecular insertion of the resultant carbene 3 into the proximal N-H bond, affords [3.2.0] bicyclic keto ester 2. Without purification, 2 is converted into enol phosphate 42 and thence into vinyl sulfide 23 (76% yield from 4).18 Finally, catalytic hydrogenation of 23 proceeds smoothly (90%) to afford ( )-thienamycin... 

Further studies revealed that the yields of l//-azepines could be increased substantially by carrying out the thermolysis of the sulfonyl azide in a nitrogen atmosphere under pressure.62-158159 For example, thermolysis of tosyl azide in benzene at 155-160 C and a nitrogen pressure of 11.5 atmospheres produced l-tosyl-l//-azepine in 5% yield, which rose to 48% under a nitrogen pressure of 82-89 atmospheres.158 The reaction temperature was critical as no azepine was formed at 140-145°C-regardless of the nitrogen pressure.160... 

The thermolysis of tosyl azide in a variety of arene substrates bearing electron-withdrawing substituents results in poor (1.5-20%) yields of the corresponding 1-tosyl-l//-azepines, e.g. 

Interestingly, prolonged (60 h) thermolysis of tosyl azide in propionic anhydride in the presence of dimethyl terephthalate produces a moderate yield of dimethyl 1-tosyl-l 7/-azepine-2,5-dicar-boxylate (18) free from the usual accompanying anilide or sulfonamide byproducts.159... 

Since the mid-1990s, synthetic attention has been directed more towards the use of metal-stabilized nitrenes as synthetic effectors of alkene aziridination. In 1969 it was reported that Cu(i) salts were capable of mediating alkene aziridination when treated with tosyl azide, but the method was limited in scope and was not adopted as a general method for the synthesis of aziridines [12]. Metaloporphyrins [13] were shown to be catalysts for the aziridination of alkenes in the presence of the nitrene precursor N-tosyliminophenyliodinane [14] in the early 1980s, but the reaction did... 

Quinone diazides can also be obtained by the diazo group transfer reaction of 4-tosyl azide. For example, 9-diazo-10-anthrone (2.55) is formed from anthrone (2.54) if the reaction is carried out in an ethanol-piperidine mixture. On the other hand, if ethanol is replaced by pyridine, dimerization with loss of molecular nitrogen takes place and the azine 2.56 is isolated (Scheme 2-32 Regitz, 1964 Cauquis et al., 1965). In the preceding discussion tosyl azide was shown to be an electrophilic reagent. It therefore seems likely that it is not the anthrone 2.54 but its conjugate base which reacts with tosyl azide. 

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 enamines176. Similar results have been reported for the reaction of 2,3-diphenylcyclopropenone with 2-diazopropane177. Other 1,3-dipolar cycloadditions with thiirene dioxides could also be affected (see below). 

Compounds containing a CH2 bonded to two Z groups (as defined on p. 548) can be converted to diazo compounds on treatment with tosyl azide in the presence of a... 

A diazo group can be introduced adjacent to a single carbonyl group indirectly by first converting the ketone to an a-formyl ketone (10-118), and then treating it with tosyl azide. As in the similar cases of 12-7 and 12-8, the formyl group is cleaved... 

In Reaction 12-9 treatment of Z—CH2—Z with tosyl azide gives diazo transfer. When this reaction is performed on a compound with a single Z group, formation of the azide becomes a competing process. " Factors favoring azide formation rather than diazo transfer include as the enolate counterion rather than Na orLi and... 

Reaction of active hydrogen compounds with tosyl azide... 

Xylene was found to be twice as reactive as benzene towards tosyl azide, and a benzene double bond eight times more reactive towards singlet sulphonyl nitrene than a carbon-hydrogen bond in cyclohexane 8>12>. 

Eight grams of the crude ester, which had been prepared from tosyl azide and sodium butoxide, then stored for four weeks at 0°C, was to be distilled at 0.2 mm Hg. On the bath reaching 70°C, there was a violent explosion. This was attributed to a toluenesulphonic acid autocatalysed elimination. However, presence of butyl azide as an impurity seems probable. 

The glutamic moiety of TNP-351, a pyrrolo[2,3-d]pyrimidine glutamic acid derivative, and related compounds have been transformed into their A-co-masked ornithine analogs which show remarkable antifolate activity <00CPB1270>. The reaction of the heterocyclic enamine 77 with tosyl azide leads to the tosylimino derivative of 1,2,4-triazolo[l, 5-a]pyrimidine 79. Extrusion of nitrogen from the primary adduct 78 is followed by a 1,2-shift of a methyl group to yield 79 <00JHC195>. 

The photochemical reaction can also proceed via the triplet state and in this case no cyclization is observed. Especially when acetophenone is added as a triplet sensitizer, 41 is not formed. Remarkable is the observation that in the presence of anthracene or pyrene as triplet quencher, the yield of the cyclization product 41 was not enhanced and that nitrene insertion into CH bonds of anthracene or pyrene was observed. When the photochemical cyclization reaction was performed with the tosyl azide derivative 42a or the azido nitrile derivative 42b (Scheme 6), only low yields of the tricyclic amide 41 (32% from 42a, 9% from 42b, respectively) were obtained <2001JCS(PI)2476>. 

Derivative 165 was treated with tosyl azide at room temperature for 48 h to give 167. Formation of this product was rationalized by a 1,3-dipolar cycloaddition with participation of the C=C bond in the pyrimidine ring in 165 to form a cycloadduct 166 at first, which underwent a [l,2]-methyl shift and a nitrogen elimination to yield 167. Stmcture elucidation of this product revealed the relative rzr-stereochemistry of the phenyl and methyl substituents. 

Thus, 5-methoxypyrimidine 103 when treated with lithium tetramethylpiperidide (LTMP) and subsequently by tosyl azide led to formation of the 2-azido derivative 104, which spontaneously undergoes ring closure to 8-methoxytetrazolo[l,5-c]pyrimidine 105. 

Diazo transfer. This azide is recommended as a relatively safe substitute for tosyl azide for diazo-transfer reactions to reactive methylene groups. Either DBU or N(C2H5)i is a suitable base. It is also suitable for synthesis of vinyl diazo compounds. 1... 

Investigations into the mechanism of this reaction revealed several interesting facts (61). Compelling evidence was presented that a discreet Cu nitrenoid was involved in the catalytic cycle. Photolysis of a solution of tosyl azide and styrene in the presence of the catalyst afforded aziridine with the same enantioselectivity as obtained from the PhI=NTs reaction, Eq. 69. Since photolysis of tosyl azide is known to extrude dinitrogen and form the free nitrene, the authors argue that this is indicative of a common Cu-nitrenoid intermediate in this reaction. 

Routes to phosphazenes involving the reaction of phosphines with carbon tetrachloride in the presence of amines have been reviewed44 and it has been shown45 that this type of reaction does not occurwithdiphosphines.lt was, however, successful with a phosphonite and tosylamine (Scheme 3).46 The same product was also obtained with tosyl azide. 

Arylamines and hydrazines react with tosyl azide under basic conditions to yield aryl azides [1] and arenes [2], respectively, by an aza-transfer process (Scheme 5.25). Traditionally, the reaction of anilines with tosyl azides requires strong bases, such as alkyl lithiums, but acceptable yields (>50%) have been obtained under liquidiliquid phase-transfer catalytic conditions. Not surprisingly, the best yields are obtained when the aryl ring is substituted by an electron-withdrawing substituent, and the yields for the corresponding reaction with aliphatic amines are generally poor (-20%). Comparison of the catalytic effect of various quaternary ammonium salts showed that tetra-/i-butylammonium bromide produces the best conversion, but differences between the various catalysts were minimal [ 1 ]. 

The formation of 3-diazo-37/-indoles from the reaction of indoles with tosyl azide is catalysed by the addition of benzyltriethylammonium chloride [22]. In the absence of the catalyst, 3,3 -azoindoles are formed to the complete exclusion of the diazoindoles. 

The reaction of activated methylene groups with tosyl azide to yield the corresponding diazo derivatives proceeds in high yield [23]. The phase-transfer catalysed reaction is sensitive to the strength of base used the reaction of acetoacetic esters requires relatively mild conditions, otherwise diazoacetic esters are produced (Table 5.41). 

OpticaUy active iV-tosylsulfoximides produced in the copper-catalyzed reaction of chiral sulfoxides with tosyl azide may be hydrolyzed with strong acid (H2SO4) to optically active free sulfoximides. However, this procedure often fails and/or results in decomposition. It is interesting to note in this connection that a simple one-step method for the preparation of optically active unsubstituted sulfoximides has been reported recently by Johnson and co-workers (180). It involves the reaction between optically active sulfoxides and 0-mesi-tylsulfonylhydroxylamine and results in sulfoximides 60 of high optical purity. As expected, this imidation process occurs with retention of configuration at sulfur. 

The starting diazoacetamide is prepared by N-arylation of /-phenylalanine methyl ester (DMP, 5.5 M 4-fluoronitrobenzene, 110°C, lOh, 30%), acetoa-cetylation (2,2,6-triraethyl-4/7-l,3-dioxin-4-one, toluene, 110 °C, 4h, 71%) and diazo group transfer (tosyl azide, triethylamine, acetonitrile, 20 °C, 1.5 h, 90%). 

Carbethoxy-4-diazo-l-phenylpyrazol-5-one (22a) (Scheme 88) was synthesized in 76% yield under mild conditions by direct introduction of the diazo group with the azidium salt 293 in sulfuric acid at room temperature [78H(10)199]. The easy introduction of the diazo group probably occurred because the a position of the ester was activated. On the contrary, tosyl azide failed to give the diazo derivative under the same conditions. Diazo transfer with this reagent only takes place under alkaline conditions, but in these reaction conditions, the diazo compound couples with the starting material. 

---