Carboxylate azides

SEI 439 f carbonyl 234, 431 Carbotron P 400 carboxyl 234 carboxylate azides 541 carboxylic groups 431... 

Curtius rearrangement of the appropriate carboxylic azides has been used to prepare 3-, and 5-amino-1,2,4-oxadiazoles <66JCS(C) 1522>. 

Dinitro-diphenylamino-4-carboxyl azide see 4-Anilino-3,5-dinitrobenzoyl azide 1 A422... 

The Curtius Rearrangement is the thermal decomposition of carboxylic azides to produce an isocyanate. These intermediates may be isolated, or their corresponding reaction or hydrolysis products may be obtained. 

An interesting, highly selective approach to both diastereomers of some aminocyclopropanes started with diesters of type 63 or 67. Saponification of 63 took place preferentially at the sterically less hindered trans- or exo-position (for references see Table 1). The free acid moiety in 64 could be transformed into an amino compound (66) via the carboxylic azide. Thereby, the ester carboxyl remained unaffected. On the other hand, the ester function of 64 could be converted into the amine (65) via the hydrazide without affecting the acid function (equation 10). Decarboxylation of 64 followed by ester amine... 

N-1 substituted carboxylic acids 201 (R = Me, = Me, X = O) are transformed into carboxylic azides 203 with 1-methylethyl chloroformate and sodium azide in DMSO (Scheme 77). Curtius rearrangement of 203 at room temperature yields isocyanates 204 that further react with nucleophiles such as ethanol to furnish urethanes 205 (75S405, 92T5473). 

Reproduction techniques. The isocyanates that are produced when aromatic carboxylic azide esters are degraded by light convert, with layers of polyvinyl alcohol, into cross-linked products with urethane groupings ... 

In synthetic target molecules esters, lactones, amides, and lactams are the most common carboxylic acid derivatives. In order to synthesize them from carboxylic acids one has generally to produce an activated acid derivative, and an enormous variety of activating reagents is known, mostly developed for peptide syntheses (M. Bodanszky, 1976). In actual syntheses of complex esters and amides, however, only a small selection of these remedies is used, and we shall mention only generally applicable methods. The classic means of activating carboxyl groups arc the acyl azide method of Curtius and the acyl chloride method of Emil Fischer. 

Acyl azides may loose N2 on heating and rearrange to isocyanates (Curtius rearrangement), which may be solvolyzed. Some of the possibilities of classical carboxyl conversions are exemplified in the schemes below, which are taken from a triquinacene synthesis (R. Russo, 1971 C. Merder, 1973) and the ergotamine synthesis of A. Hofmann (1963). 

The main example of a category I indole synthesis is the Hemetsberger procedure for preparation of indole-2-carboxylate esters from ot-azidocinna-mates[l]. The procedure involves condensation of an aromatic aldehyde with an azidoacetate ester, followed by thermolysis of the resulting a-azidocinna-mate. The conditions used for the base-catalysed condensation are critical since the azidoacetate enolate can decompose by elimination of nitrogen. Conditions developed by Moody usually give good yields[2]. This involves slow addition of the aldehyde and 3-5 equiv. of the azide to a cold solution of sodium ethoxide. While the thermolysis might be viewed as a nitrene insertion reaction, it has been demonstrated that azirine intermediates can be isolated at intermediate temperatures[3]. 

Solvent for Displacement Reactions. As the most polar of the common aprotic solvents, DMSO is a favored solvent for displacement reactions because of its high dielectric constant and because anions are less solvated in it (87). Rates for these reactions are sometimes a thousand times faster in DMSO than in alcohols. Suitable nucleophiles include acetyUde ion, alkoxide ion, hydroxide ion, azide ion, carbanions, carboxylate ions, cyanide ion, hahde ions, mercaptide ions, phenoxide ions, nitrite ions, and thiocyanate ions (31). Rates of displacement by amides or amines are also greater in DMSO than in alcohol or aqueous solutions. Dimethyl sulfoxide is used as the reaction solvent in the manufacture of high performance, polyaryl ether polymers by reaction of bis(4,4 -chlorophenyl) sulfone with the disodium salts of dihydroxyphenols, eg, bisphenol A or 4,4 -sulfonylbisphenol (88). These and related reactions are made more economical by efficient recycling of DMSO (89). Nucleophilic displacement of activated aromatic nitro groups with aryloxy anion in DMSO is a versatile and useful reaction for the synthesis of aromatic ethers and polyethers (90). 

A number of compounds of the types RSbY2 and R2SbY, where Y is an anionic group other than halogen, have been prepared by the reaction of dihalo- or halostibines with lithium, sodium, or ammonium alkoxides (118,119), amides (120), azides (121), carboxylates (122), dithiocarbamates (123), mercaptides (124,125), or phenoxides (118). Dihalo- and halostibines can also be converted to compounds in which an antimony is linked to a main group (126) or transition metal (127). 

The procedure described is essentially that of Shioiri and Yamada. Diphenyl phosphorazidate is a useful and versatile reagent in organic synthesis. It has been used for racemlzatlon-free peptide syntheses, thiol ester synthesis, a modified Curtius reaction, an esterification of a-substituted carboxylic acld, formation of diketoplperazines, alkyl azide synthesis, phosphorylation of alcohols and amines,and polymerization of amino acids and peptides. - Furthermore, diphenyl phosphorazidate acts as a nitrene source and as a 1,3-dipole.An example in the ring contraction of cyclic ketones to form cycloalkanecarboxylic acids is presented in the next procedure, this volume. 

Recently Hofmann has found that when the azide hydrochlorides of the lysergic and fsolysergic acids, or of their dihydro-derivatives, are boiled in dilute hydrochloric acid, a Curtius reaction occiys and the carboxyl is replaced by an amino-group. In this way he has prepared the following amines. They melt with decornposition and the specific rotations are for pyridine as solvent — ... 

The methyl ester (100, R = CH3), derived from this A-nor acid by treatment with diazomethane, is different from the ester (102) obtained either by Favorskii rearrangement of 2a-bromo-5a-cholestan-3-one (101) or by the action of cyanogen azide on 3-methoxy-5a-cholest-2-ene (103) followed by hydrolysis on alumina. The ketene intermediate involved in photolysis of (99) is expected to be hydrated from the less hindered a-side of the molecule to give the 2j -carboxylic acid. The reactions which afford (102) would be expected to afford the 2a-epimer. These configurational assignments are confirmed by deuteriochloroform-benzene solvent shifts in the NMR spectra of esters (100) and (102). ... 

Early attempts to prepare 5-amino- and 5-acylaminobenzofuroxans by hypochlorite oxidation of the corresponding o-nitroanilines met with failure. Pyrolysis of the appropriate azide, however, gives 5-dimetliylamino- and 5-acetamidobenzofuroxan, whereas urethans of type (33) are produced by Curtius degradation of the 5-carboxylic acid. Controlled hydrolysis of the acetamido compound and the... 

Carboxylic acid derivatives can be converted into primary amines with loss of one carbon atom by both the Hofmann rearrangement and tire Curtius rearrangement. Although the Hofmann rearrangement involves a primary-amide and the Curtius rearrangement involves an acyl azide, both proceed through similar mechanisms. 

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... 

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... 

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