Azidophenyl

Treatment of resin-bound iminophosphorane 197 with an excess of solid CO2 and CS2 in a sealed glass tube, and with aryl isocyanates afforded I-OXO-, 1-thioxo- 198, and l-arylimino-l//-pyrido[l,2-c]pyrimidine-3-car-boxylates 199 (OlJMClOll). Reaction of iminophosphorane 200, derived from 2-(2-azidophenyl)pyridine with excess PPh3, yielded 6//-pyrido[l,2-c] quinazoline-6-thione (201). 

Example 2 a-Azidobenzylpenicillin via the Acid Chloride — 6-aminopenicillanic acid (18.5 grams, 0.085 mol) and sodium bicarbonate (21 grams, 0.025 mol) were dissolved in 200 ml of water and 100 ml of acetone. To this solution, chilled in ice, was added a-azidophenyl-acetyl chloride (16.6 grams, 0.085 mol), diluted with 10 ml of dry acetone. The temperature is held at 0° to 5°C and the reaction mixture was stirred for 2 A hours. 

A comparison of the photolysis of 2-azidophenyl methyl ketone and 3-methyl-2,1-benzisoxazole in piperidine reveals that whereas the former gives a mixture of isomeric 3//-azepines the latter furnishes 3-acetyl-2-piperidino-3/7-azepine (4) in almost quantitative yield.124... 

The thermolysis of 4-azidophenyl methyl ketone in morpholine at 170°C yields a mixture of the expected 5-acetyl-2-morpholino-3f/-azepine (33) and 6-acetyl-2-morpholino-3//-azepine (34), the product of a unique and totally unexpected thermal rearrangement of the 5-acetyl derivative.119 Similar results can be obtained in hot piperidine, whereas thermolysis of 4-azido-diphenyl ketone under similar conditions yields only the 6-benzoyl-2-(cycloalkylamino)-3//-azepines (7-18%) accompanied by much tar. 

The thermolysis of aryl azides in alcoholic solution has been used to prepare 2-alkoxy-37f-azepines. Thermolysis of 3-azidophenyl methyl ketone in methanol in a sealed ampule furnishes a mixture of the 6-acetyl- (36a) and 4-acetyl-2-methoxy-3//-azepine (37a) in superior yields to those obtained in the corresponding photolytic reaction.78 Other 3-substituted azides behave similarly, with a preference for the 6-substituted isomers 36, as is observed for azide photolyses in amine solutions. 

Likewise, thermolysis of 4-azidophenyl methyl ketone in methanol yields 5-acetyl-2-methoxy-3//-azepine (60%), compared to only an 8% yield from the photolytic reaction.78 119 The thermolysis of phenyl azide in refluxing cyclohexanol yields no 3H-azepine, only diphenyl-diazene (10%) and aniline (30%).74 In contrast, thermolysis of methyl 2-azidobenzoate in cyclohexanol furnishes a mixture of methyl 2-(cyclohexyloxy)-3//-azepine-3-carboxylate (20 % bp 127°C/0.1 Torr) and methyl 2-aminobenzoate (60%). Thermolysis of the azido ester in methanol under nitrogen in an autoclave at 150 C yields a 7 10 mixture (by 1HNMR spectroscopy) of the amino ester and methyl 2-methoxy-3//-azepine-3-carboxylate, which proved to be difficult to separate, and much tar.74 The acidic medium179 is probably responsible for the failure of methyl 2-azidoberjzoate to yield a 3//-azepine when thermolyzed in 3-methoxyphenol aniline (40%) is the major product.74... 

The photolysis of 2-azidophenyl methyl ketone in piperidine yields 3-acetyl-2-piperidino-3//-azepine (18 % mp 67-68 CC) in admixture with a lesser amount of the regioisomeric 2-acetyl-7-piperidino-3f/-azepine (12% bp 100l C/0.05 Torr) 125 2-azido-4-tolyl methyl ketone behaves similarly. 

Few heteroaryl-substituted 37/-azepines are known however, photolysis of 2-(2-azidophenyl)-pyridine (80) in diethylamine provides Ar,Ar-diethyl-3-(2-pyridyl)-3/f-azepin-2-amine(81), along with minor amounts of pyrido[3,2-6]indole (82) and the mesoionic pyridofl, 2-7>]indazole (83).191... 

Similarly, photolysis of l-(2-azidophenyl)-l/f-pyrazole in acetonitrile in the presence of dipropylamine affords AfN-dipropyl-7-(lF/-pyrazol-l-yl)-3//-azepin-2-amine in low yield (4%).192 Surprisingly, however, photolysis of the corresponding 1-(2-azidophenyl)-3,5-dimethyl-l//-pyrazole (84) in cyclohexane in the presence of the base yields 85 which, on the basis of H NMR spectroscopic evidence, has been formulated as a rare example of a stable 2 H-azepine. 

Cyanophenyl azide is of interest in that on photolysis in methanol/tetrahydrofuran solution, an unseparated 1 1 mixture (by HNMR spectroscopy) of 2-methoxy-3//-azepine-3-carbonitrile and -7-carbonitrile (44%) is formed.197-282 Likewise, irradiation of 2-azidophenyl methyl ketone in methanol furnishes a mixture of 3-acetyl-2-methoxy- (11 %) and 7-acetyl-2-methoxy-3//-azcpine (3%) along with 3-methyl-2,l-benzisoxazole (18%).78... 

Internal nitrenes normally react at the adjacent position. Reduction of 2-(2-nitrophenyl)furan by ethyl phosphite yields furoindole derivatives in fair yield (34%) only, whereas much better results attend the pyrolysis of 2-(2-azidophenyl)furan.280 Furopyrazoles are obtained similarly.281 Azidofurans yield nitrenes that insert into adjacent CH links to form furo-pyrroles.282 Quite different results attend either the pyrolysis or the photolysis of azide 107a for the expected insertion into the side chain occurs giving the related indole but it is accompanied by the surprising replacement of furan oxygen by nitrogen producing 107b and similar products.283... 

SADP, N-succinimidyl-(4-azidophenyl)l,3 -dithiopropionate, is a photoreactive heterobifunctional crosslinker that is cleavable by treatment with a disulfide reducing agent (Thermo Fisher). The crosslinker contains an amine-reactive NHS ester and a photoactivatable phenyl azide group, providing specific, directed coupling at one end and nonselective insertion capability at the other end. 

The reactions of APDP are similar to that of the reported compound N-(4-azidophenyl) thiophthalimide, a non-radioiodinatable crosslinker (Moreland et al., 1982). Both the phenyl... 

Politz, S.M., Noller, H.F., and McWhirter, P.D. (1981) Ribonucleic acid-protein cross-linking in Escherichia coli ribosomes (4-azidophenyl) glyoxal, a novel heterobifunctional reagent. Biochemistry 20, 372-378. 

Prostaglandin receptors, including prostacyclin (PGI2), are all G-protein coupled receptors, which activate cAMP cyclase, resulting in cAMP. PGI2 receptors were identified in mouse mastocytoma P-815 cells (43 kDa) by a photolabile analogue, [15-3H]-19-(3-azidophenyl)-20-norisocarbacyclin (21, Fig. 10). The photoprobe also labeled a 45-kDa band in membranes of procine platelets [98]. 

Esters of 2-(2-azidophenyl)ethyl alcohol are photolyzed under a high-pressure mercury lamp to a reactive nitrene intermediate which, following insertion into the alkyl side-chain, undergoes elimination to give the free carboxylic acid (up to 32%) and producing indole. The photochemical release was somewhat improved (65-80%) when 5-azido-4-(hydroxy-methyl)-l-methoxy naphthalene was used (see Scheme 27). 

Scheme 27.—Photocyclization of 2-(2-Azidophenyl)ethyl Esters and 5-Azido-4-(hy-droxymethyl)-l-methoxynaphthalene Esters.

Isomeric l,3a,4,6a- (220) and l,3a,6,6a- (91) dibenzotetraazapentalenes can be prepared from the thermal decomposition of 2-((9-azidophenyl)-2//-benzotriazole (224) and - o-azidophenyl)-2//-benzotriazole (230), respectively, in high boiling solvents such as 0-dichlorobenzene and decalin. This synthesis was improved upon when it was found that (220) and (91) can be prepared from the reactions of 2-((9-nitrophenyl)-2//-benzotriazole (226) and l-(o-nitrophenyl)-2//-benzotriazole (229), respectively, with triethyl phosphite in refluxing xylene. ... 

This also may be looked upon as a substituent reaction (see Chapter 2.06) but a few examples are given here. A suitably substituted pyridine will undergo Pschorr cyclization to give 2- and 4-azafluorene and two other products (equation 181) (65CJC940). With a 2-substituted pyridine (287), cyclization on to the pyridine nitrogen is heavily favoured (equation 182) (54JCS4263). Decomposition of 3-(o-azidophenyl)pyridine results in a nitrene... 

C2Hs.C H.4.(Na) mw 147.17, N 28.54%. Refs were found only for a- and p-azidophenyl-ethanes. No refs to o-, m- or p-azidophenyl ethanes were found... 

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