Azidoacetyl chloride

The interaction of acid chlorides (167 X = Cl) with imines in the presence of bases such as triethylamine may involve prior formation of a ketene followed by cycloaddition to the imine, but in many cases it is considered to involve interaction of the imine with the acid chloride to give an immonium ion (168). This is then cyclized by deprotonation under the influence of the base. Clearly, the distinction between these routes is a rather fine one and the mechanism involved in a particular case may well depend on the reactants and the timing of mixing. Particularly important acid chlorides are azidoacetyl chloride and phthalimidoacetyl chloride, which provide access to /3-lactams with a nitrogen substituent in the 3-position as found in the penicillins and cephalosporins. 

Scientists at Merck developed a cephalosporin synthesis based on the addition of azidoacetyl chloride to 1,3-thiazines (56). Although this gives the incorrect 7a -epimer (57), it could be equilibrated to a mixture of 7-amino epimers (see Section 5.10.3.3) from which the desired 7/3-isomer could be separated and further elaborated to cephalosporins (B-82MI51001). 

Another synthetic sequence leading to penicillin derivatives is illustrated in Scheme 61 (77MI51102). Note that the cycloaddition of azidoacetyl chloride to the thiazoline affords an azidopenam with the 6-epi configuration. Equilibration leads to a mixture of (81) and (82) in a ratio of 4 1, but repeated recycling allowed the isolation of (82) in 40% yield. A related synthesis was shown in Scheme 26. 

Azidoacetyl chloride See other 2-azidocarbonyl compounds, organic acids... 

Azidoacetonitrile, 0714 Azidoacetyl chloride, 0693 4-Azidobenzaldehyde, 2697 7-Azidobicyclo[2.2.l]hepta-2,5-diene, 2777 Azido-2-butyne, 1473... 

Diazidoacetic Anhydride, NrHaC.OC.O.CO. CHj.Nj, mw 184.12, N45.65%. Col oil, bp 110° at 0,2 mm. Indexed in CA as Triazoacetic Acid Anhydride. Prepd by shaking an abs ether suspension of the Ag salt of azidoacetic acid with a soln of azidoacetyl-chloride in abs ether... 

Acetyl chloride and derivs 1 A56-AS6 azidoacetyl chloride 1 AS 7 nitroacetyl chloride 1 A57... 

Azidoacetyl Chloride See Vol 1, p A57-L Barium Chloride, BaCl2 mw 208.27, monoclinic or cubic crysts mp 960°... 

COOH, mw 221.17, N19.00%. Col crysts, mp 104 easily sol in alc,acet, EtOAc, eth, chlf diff sol in w. Was prepd by treating salicylic acid with azidoacetyl-chloride in chlf and pyridine. No mention... 

Azidoacetyl-dl-olonine Chloride. See under Acetylalanine and Derivatives, p A54 Azidoacetyl Chloride. See under Acetyl Chloride and Derivatives, p A57... 

In the course of their studies on the synthesis of ot-amido-spiro-(5-lactams as analogs of penicillin and cephalosporin, Manhas et al. [76] have prepared 1-phenyl-3-phenoxy-4,4-spirocyclohexylazetidin-2-ones by the reaction of phenoxyacetyl chloride 7 and cyclohexylidenephenylamine 8 in the presence of triethylamine and dichloromethane. Azidoacetyl chloride was found to be even more reactive... 

Azidoacetaldehyde, 0768 Azidoacetic acid, 0770 Azidoacetone oxime, 1211 Azidoacetonitrile, 0710 Azidoacetyl chloride, 0689 4-Azidobenzaldehyde, 2693 Azidobenzene, see Phenyl azide, 2264 7-Azidobicyclo[2.2.1]hepta-2,5-diene, 2773 2-Azido-1,3-butadiene, 1468 Azido-2-butyne, 1469... 

An approach to obtain racemic 7-ACA and its 7-epimer has been achieved employing a Staudinger-Bose ketene-imine cycloaddition to form the /3-lactam ring <1996T7691> (Scheme 18). Reaction of azidoacetyl chloride and thiazine 75 in the presence of 7-Pr2NEt afforded azidocephem 76 in 38% yield. Compound 76 was reduced to amine... 

This synthesis requires the separation of the diastereoisomers of 92 (obtained from D-penicillamine). An attempt to control the stereochemistry was developed by the Merck group in 1974, in a total synthesis based on the [2+2] cycloaddition of the ketene derived from azidoacetyl chloride and the chiral thiazoline 94. The reaction only gives the /ra .r-pcnam derivative 95, which could be epimerized via the Schiff base 96 (cisltrans ratio = 2 1) (Scheme 51). The separated tyr-isomcr has been transformed into synthetic penicillin G <1974JOC437>. 

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