Pentyne, l-chloro

The well documented synthetic method for 37 is chlorination of cyclopropyl-methylketone followed by base treatment [29]. However, this method did not provide a suitable impurity profile. The most convenient and suitable method we found was the one-step synthesis from 5-chloro-l-pentyne (49) by addition of 2equiv of base, as shown in Scheme 1.18 [21, 30]. Two major impurities, starting material 49 and reduced pentyne, had to be controlled below 0.2% each in the final bulk of 37, to ensure the final purity of Efavirenz . Acetylene 37 was isolated by distillation after standard work-up procedure. 

Presence of a certain type of functional groups in alkynes does not interfere with silylformylation. For example, the chlorine atom in 5-chloro-l-pentyne 44 and the cyano group in 5-cyano-l-pentyne 46 do not affect the silylformylation to give 45 and 47 respectively (Equations (10) and (11)). 4-Bromo-l-butyne and 6-bromo-l-hexyne also give the corresponding silylformylation products." ... 

To 3-aniino-4-iodopyridine (10.00 mmol) dissolved in 25 ml acetonitrile was added 1.67 ml trifluoroacetic anhydride at 0°C and KjCOj (30 mmol) and the mixture stirred 10 minutes at ambient temperature. To this was added bis(triphenylphosphine)-palladium(n)chloride (0.25 mmol), copper(I)iodide (0.50 mmol), and 5-chloro-l-pentyne (12.00 mmol) and the mixture refluxed 3 hours. Thereafter, the mixture was cooled, partitioned between water and EtOAc, and the organic phase extracted with water at pH 1.00. The aqueous phase was mixed with CH2CI2 and the pH raised to 10 by the addition of 2M NaOH. The organic phases were combined, dried, concentrated, and the residue dissolved in 20 ml acetonitrile. To this brownish solution was added Nal (20 mmol) and NaH (ca 55%, 20 mmol), the mixture stirred 2 hours, poured onto ice, partitioned between 100 ml apiece of water and EtOAc, and the phases separated. The organic phase was extracted 5 times with 50 ml water at pH 1.00, mixed with 100 ml CH2CI2, and the pH raised to 10 using 2M NaOH. The phases were separated, the organic phase dried, concentrated and the product isolated in 51% yield, mp = 95-96 °C after re-crystallization in t-butyl-methylether. Elemental analysis data supplied. 

Chloro-l-pentyne Propionaldehyde 8-Chloro-trans-4-octen-3-ol 47... 

The azide-alkyne click reactions are useful to attach a number of polar FGs including various azobenzene moieties to the pendants of poly(l-phenyl-5-chloro-l-pentyne), (Eq. (7)) [90]. Nucleophilic substitutions of the same starting polymer result in the formation of an imidazole-functionalized, disubstituted acetylene polymer, (Eq. (8)) [91]. The degree of incorporation of the imidazole moiety is about 65%, and the product polymer exhibits good solubility in ethanol. Hydrolysis reaction of poly[l-(/w-methoxycarbonylphenyl)-l-octyne] yields a carboxy-functionalized disubstituted acetylene polymer poly[l-(/w-carboxyphenyl)-l-octyne], (Eq. 9) [92]. Hydrazine-catalyzed deprotection of poly[l-phenyl-ll-Af-benzimide-l-undecyne] affords the corresponding polyamine, which can be further ionized with hydrobromic acid to give a polyelectrolyte ammonium salt, (Eq. (10)) [93]. 

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