Ethyl with azide

The acyl azide intermediates are prepared either by reaction of sodium azide with a reactive acylating agent or by diazotization of an acyl hydrazide. An especially convenient version of the former process is treatment of the carboxylic acid with ethyl chloroformate to form a mixed anhydride, which then reacts with azide ion.265... 

Enamines contain electron-rich double bonds and thus react readily with azides (in many cases at room temperature). Only one addition product is formed, namely a 5-amino-A2-triazoline, a result of electronic control.22 -223 Thus l-(p-nitrophenyl)-4-ethyl-5-morpholino-A2-triazoline (44) arises from the addition of p-nitrophenyl azide to 1-morpholino-l-butene (43). The addition products rearrange by heating into amidines (45).224... 

The acid-catalyzed hydrolysis of -methylstyrene oxide (38a) in azide solutions has also been studied, but the yields of azido alcohols are only very slightly greater than the yields predicted if all of the azido alcohol is formed from the bimolecular (fcN) pathway.41 For example, in water containing 0.025 M azide ion, pH 5.75, the observed yield of azido alcohol from 38a is 22%. The calculated yield from the bimolecular reaction is 19%. This yield is very close, perhaps within experimental error, to that expected from only the bimolecular pathway (kN). If it is assumed that 3% of azido alcohol is actually from trapping of the intermediate carbocation 39a with azide ion, then a lower limit of 3 x 109 s 1 can be estimated for ks. This value is fortuitously close the value of ks estimated for reaction of l-(p-methylphenyl)ethyl carbocation with 50 50 TFE/H20 (4 x 109 s 1), and is most likely an underestimate. 

As part of a project to synthesize stable analogs of the indole-2,3-quinodimethane system, the 2,4-di-hydropyrrolo[3,4]indole (251) has been prepared from formylindole (249). Knoevenagel condensation with ethyl malonate followed by bromination and nucleophilic substitution of the bromide with azide yields (250), which immediately undergoes intramolecular 1,3-dipolar cycloaddition to give the triazoline (252). Treatment of (252) with toluene-p-sulfonic acid affords diethyl diazomalonate and (251 ... 

On decomposition of the 1 1 adduct of phenyl azide with both alkyl aluminum chlorides, the main reaction is A-ethylation with the formation of IV-ethylanilides 100). 

Ethyl diethoxyphosphinylpropynoate (122) can act as a good dienophile it also reacts with azides to form C-phosphorylated-l,2,4-triazoles. Amines add to l,2-bis(dialkoxyphosphinyl)acetylene to give the enamines (123) when the latter are derived from primary amines, they can be C-alkylated via their lithio derivative. ... 

The reactivity of the ethenediazonium salt 9.100 towards the nucleophiles mentioned shows that it has the properties of the corresponding carbocation, since it can ethylate the nucleophile and is prone to attack at the C()ff)-atom of the original ethene-l-diazonium ion. The thermal decomposition pattern is typical of that for an oxonium salt. Reactions with amines are similar to those of ketene acetals. No product that could be explained in terms of an azo coupling reaction, e.g., with 2-naphthol, could be observed. The electrophilicity of the diazonio group is, therefore, low. N-Azo coupling products with azide ions have been postulated with good arguments, however, by Kirmse and Schnurr (1977) with certain short-lived ethene diazonium intermediates produced from nitroso oxazolidones. 

The synthesis of 8-azapurine analog 330 was done by the chloroalkylation of the alcohols 265 followed by replacement of chlorine with azide to give 327. Cyclization with cyanoacetamide gave the 1,2,3-triazoline 328. Deprotection formed 329, and cyclization of 328 with ethyl formate and deprotection gave 330 (88S879). The same strategy was used to prepare analogs of types 2.2 and 3.1. 

Hydroxyvaline 265 has been prepared by stereoselective opening of cyclic sulfate 263 with azide ion to give ethyl a-azido-/3-hydroxy-4-methylpentanoate 264, which was reduced by Pd(OH)2/H2—CH3OH (94T9181) (Scheme 67). 

A further report on the synthesis of AZT describes the reaction of anhydro-nucleoside 28, prepared in a new way, with azide ion. 3 -Azido-2-0-ethyl-2, 3 -... 

Three new synthetic methods for the conversion of alcohols into azides (and hence potentially into amines) have been published. One route involves a further application of the chemistry of 2-alkoxypyridinium salts (formed in situ from an alcohol and the 2-fluoropyridinium salt) in their reaction with azide ion " (Scheme 17). Another extends the utility of the triphenylphosphine-ethyl diazodicarboxylate system, using diphenylphosphoryl azide as azide donor (Scheme 18), but is sensitive to steric hindrance at the alcohol carbon. The third route (Scheme 19) achieves oxygen activation through the alkoxyphosphonium salts (39), which are prepared from the alcohol, a phosphine, and a positive halogen donor such as carbon tetrachloride (with primary alcohols) or Af-chlorodi-isopropylamine (in... 

In another approach, commercially available ethyl fran.y-cinnamate was used as starting material, and similar chemistry to that described above was performed, except that the cyclic sulfite 7.2.16 was opened directly with azide instead of being oxidized to sulfate the resulting azidoalcohol 7.2.17 had the opposite stereochemistry at C-2. The stereochemistry at C-2 was inverted by the Mitsonobu procedure to give... 

Azido-sugars are frequently prepared by reaction of epoxides with azide ion. 3-Azido-3-deoxy-L-threose 68 was synthesized from cu-but-2-ene-l,4-diol 66 via the Sharpless asymmetic epoxidation product 67, and was converted into 6-azido-6-deoxy-L-galocro-heptulose 69 by an enzyme-catalyzed aldol condensation (Scheme 13). 3-Azido-3-deoxy-L-etythrose, and thence 6-azido-6-deoxy-L-g/uco-heptulose were obtained in a similar way via 4-rerf-butyldiphenylsilyoxy-rraiu-but-2-enal. These and two other azido-heptulose isomers made from the enantiomeric 3-azido-3-deoxy-tetroses, were converted to a- and P-l-homonojirimycin and homomannonojirimycin on hydrogenation. Ethyl 3-azido-2,3-dideoxy-D-eryr/iro-pentopyranoside and its 3-C-methyl analogue 71, R=H or Me, were synthesized from crotonaldehyde or 3-methyl-2-... 

Consider, for example, the production of ethyl azide by the reaction of bromo-ethane with azide anion (N3 ) (Table 7.5i). A representation of the pathway over which the reactants must pass, the transition state between reactants and products, and the products themselves is provided in Rgures 7.10 and 7.11. 

Figure 7.10. A representation of an energy diagram for the Sn2 reaction of 2-bromoethane (ethyl bromide, CH3CH2Br) with azide anion (Ns"). This three-dimensional figure can be transposed into two dimensions as shown in Figure 7.11.

Figure 7.11. A two-dimensional representation of the energy diagram of Figure 7.10. In the example, bromoethane (ethyl bromide [CH3CH2Br]) undergoes reaction with azide anion (Nj ) producing ethyl azide (CH3CH2N3) and bromide (Br ) anion.

The easiest organic azide and smallest member of azidomethanes, CH3N3, was first prepared by O. Dimroth in 1905 by simple methylation of sodium azide with dimethyl sulfate. Methyl azide has been proven to be more explosive than originally reported (same accounts for ethyl azide). The much more hazardous diazidomethane, CH2(N3)2 and triazidomethane, CH(N3)3, are accessible by rather time-consuming slow reactions of dichloro/dibromomethane and tribromomethane with a polymeric ammonium azide reagent. Several reports on the potential risk when working with azides in dichlorometh-ane exist, and are attributed to the potential formation of diazidomethane (please see appropriate references cited in ref. °). 

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