Addition to azides

Ethyl cyanoformate is an effective dipolarophile undergoing 1,3-dipolar addition to azides, for example with ethyl azidoacetate to afford tetrazoleacetic acid derivatives (Ref. 45). Tetrazoleacetic acid is a key starting material for the preparation of pharmaceuticals such as the antibiotic Cefazolin [Scheme 48],... 

At elevated temperature, the azides 245 react with acetylenedicarbonic esters leading to 4,5-dicarbonic acid esters Dipolar additions to azide... 

Cefazolin [25953-19-9], antibiotic, 54. The key intermediate, tetrazole-1-acetic acid ethyl ester 53 is prepared with pivaloyl chloride [44] or ethyl cyanofbrmate 50 (an effective dipolarophile undergoing 1,3-dipolar addition to azide 51) [45],... 

The advent of azide/alkyne click chemistry, reintroduced by Sharpless and Meldal earlier this century, has prompted an avalanche of publications in the fields of biochemistry, material science and biopolymers. As of 2008, more than 1000 publications on this subject are listed on the Sharpless website. I have noticed that gradually other [3+2] and [4+2] cycloaddition reactions are included, indicating that cycloaddition chemistry is useful for construction and modification of biopolymers. Especially, the [3+2] Huisgen chemistry is useful because in addition to azides many other 1,3-dipolar species react with dipolarophiles at room temperature and the yields often approach quantitative. There is also renewed interest in [4+2] Diels-Alder chemistry. 

Cycloadditions. Methyl and ethyl cyanoformate have been reported to undergo [4 + 2] cycloadditions, e.g. with cyclopentadienones and 2-alkyl-l-ethoxybuta-1,3-dienes to form pyridines (eq 21), and with cyclobutadienes to form Dewar pyridines (eq 22). Ethyl cyanoformate is also ein effeetive dipolarophile, undergoing 1,3-dipolar addition to azides (eq 23) and cyclic carbonyl ylides (eq 24). ... 

The mammoth growth in the field of organocatalytic reactions has paved the way for an alternate synthetic approach that can eventually reach large-scale applications for the synthesis of various pharmaceuticals. Further, due to limited availability of structurally diverse alkynes, attention was focused onto the simple carbonyl compounds, considering carbonyl group as the nucleophilic source for generating an active species for addition to the azide. A handful of articles have been reported wherein activated carbonyls were converted to preformed enolates, which then underwent addition to azide to generate 1,2,3-triazoles. 

This following article was sent to Strike by Osmium and Feck (are they the same person ). It involves the direct addition of azide to a terminal alkene (you-know-who) by the in situ production of the reactant mercury (II) azide from mercuric acetate and sodium azide (please don t ask) [80]. 

That looks simple and direct don t it If safrole was used as the alkene one would get safrole-azide as product. Just one teensy little reduction away from MDA. Strike also found some azide papers that, with a little work, will get safrole-azide in a totally different way. Strike came across a lot of work where groups were using dinucleophilic addition to get an azide and a halogen added across a double bond. The azide would always go to the beta secondary carbon and the halogen to the primary carbon (just what one would want if safrole was the substrate). 

Lead azide is not readily dead-pressed, ie, pressed to a point where it can no longer be initiated. However, this condition is somewhat dependent on the output of the mixture used to ignite the lead azide and the degree of confinement of the system. Because lead azide is a nonconductor, it may be mixed with flaked graphite to form a conductive mix for use in low energy electric detonators. A number of different types of lead azide have been prepared to improve its handling characteristics and performance and to decrease sensitivity. In addition to the dextrinated lead azide commonly used in the United States, service lead azide, which contains a minimum of 97% lead azide and no protective colloid, is used in the United Kingdom. Other varieties include colloidal lead azide (3—4 pm), poly(vinyl alcohol)-coated lead azide, and British RE) 1333 and RE) 1343 lead azide which is precipitated in the presence of carboxymethyl cellulose (88—92). 

Diphenylthiirene 1-oxide reacts with hydroxylamine to give the oxime of benzyl phenyl ketone (79JA390). The reaction probably occurs by addition to the carbon-carbon double bond followed by loss of sulfur monoxide (Scheme 80). Dimethylamine adds to the double bond of 2,3-diphenylthiirene 1,1-dioxide with loss of sulfur dioxide (Scheme 81) (75JOC3189). Azide ion gives seven products, one of which involves cleavage of the carbon-carbon bond of an intermediate cycloadduct (Scheme 81) (80JOC2604). 

Salts. In addition to the dangers of perchlorate salts, other salts such as nitrates, azides and diazo salts can be hazardous and due care should be taken when these are dried. Large quantities should never be prepared or stored for long periods. 

Iodine azide is a highly selective reagent addition to the 16-double bond of androsta-4,16-diene-3-ones is possible and some selectivity in addition to the 16-double bond of A -dienes has been observed.Hydroxy groups in the steroid should be protected, e.g., by acetylation, since in some instances oxidized side products are formed. 

Although chlorine azide and bromine azide tend to give some dihalogen adducts, these reagents have been used in the presence of alcohol, ester and epoxy functions without interference.In the case of 17a-acetoxy-A -progesterone, a selective addition to the 6,7-double bond is obtained. ... 

Bromine azide addition to testosterone esters is achieved by the same procedure with the use of //-bromosuccinimide. 

Some 1,3-dipolar cycloadditions to hetero ft bond systems have been reported, including a couple of examples of additions of azides to the activated nitrile function of tnfluoroacetonitrile [30, 3I (equation 27)... 

The 1,2,3,4-thiatriazoles are unstable. They decompose on heating— in some cases even at room temperature—and in many cases they melt with detonation. Accordingly the Ng-group has not been stabilized much by ring closure. The compounds behave in this respect similarly to azides and this fact doubtlessly delayed the recognition of their true nature. On heating with a solvent the thermal decomposition of 5-aryl-1,2,3,4-thiatriazoles proceeds according to Eq. (4). By the photochemical decomposition small amounts of the isothiocyanate, RNCS, are formed in addition to the nitrile. ... 

Because of resonance stabilization of the anion, a tet-nazolyl moiety is often employed successfully as a bioisosteric replacement for a carboxy group. An example in this subclass is provided by azosemide (27). Benzonitrile analogue is prepared by phosphorus oxychloride dehydration of the corresponding benzamide. Next, a nucleophilic aromatic displacement reaction of the fluorine atom leads to The synthesis concludes with the 1,3-dipolar addition of azide to the nitrile liinction to produce the diuretic azosemi de (27). ... 

Various nucleophiles undergo addition to oxepins to give functionalized cyclohexadienols. Thus, terf-butyl oxepin-4-carboxylate when treated with a methanolic solution of lithium hydroxide gives /ert-butyl ow .v-5-hydroxy-6-methoxycyclohexa-l,3-diene-1-carboxylate (3a) in 56% yield.156 When dioxane is used as solvent, the respective dihydroxy derivative 3b is obtained in 30 % yield. Sodium azide reacts with oxepin to give mws-6-azidocyclohexa-2,4-dien-l-ol (3c) in 55% yield.212... 

Thermolysis of the azide 15, bearing an allyl side chain, is more complex, and in addition to ethyl 4-allylindole-2-carboxylate and ethyl 4-methyl-l//-3-benzazepine-2-carboxylate (16 oil), two unstable tricyclic aziridines 17 and 18 are produced.82 A mechanistic rationale for these results has been suggested. 

The reaction of 1030 with nitrous acid led, through azide 1031, to labeled 1032. The proposed angular structure 1032 is the major component both in solution and in the solid state. By means of 13C-NMR, a ternary equilibrium was detected in dimethyl sulfoxide, which involves 1032 as the main compound in addition to 1031 and the linear isomer present in smaller... 

Neugen. Polyethylene glycol laurate used as an additive to prevent the expi reaction of Ba azide. See under Barium Diazide in Vol 1, A524-L... 

Among the experiments that have been cited for the viewpoint that borderline behavior results from simultaneous SnI and Sn2 mechanisms is the behavior of 4-methoxybenzyl chloride in 70% aqueous acetone. In this solvent, hydrolysis (i.e., conversion to 4-methoxybenzyl alcohol) occurs by an SnI mechanism. When azide ions are added, the alcohol is still a product, but now 4-methoxybenzyl azide is another product. Addition of azide ions increases the rate of ionization (by the salt effect) but decreases the rate of hydrolysis. If more carbocations are produced but fewer go to the alcohol, then some azide must he formed by reaction with carbocations—an SnI process. However, the rate of ionization is always less than the total rate of reaction, so some azide must also form by an Sn2 mechanism. Thus, the conclusion is that SnI and Sn2 mechanisms operate simultaneously. ... 

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