1,2,3 triazole primary alcohols

Several new methods for the preparation of 1,2,3-triazoles were reported in 1997. Thus, various N-alkyl benzotriazoles have been prepared via a Mitsunobu-like transformation involving treatment of primary alcohols with PhaP and NBS followed by benzotriazole <97SC1613>. 2-Aryl-2H-benzotriazoles 73, used as ultraviolet absorbers, were prepared in excellent yield by the reductive cyclization of o-nitrophenylazobenzenes 72 by Sml2 in THF under mild conditions <97TL8303>. 

Triazoles are obtained via 1,3-dipolar cycloadditions between azides and al-kynes, and they are probably the most common nitrogen heterocycles prepared on solid supports via 1,3-dipolar cycloaddition. A wide variety of 1,2,3-triazoles have been prepared on solid supports, with an alkyne or azide attached to the resin. In addition, various linkers have been studied. Alkyne-functionalized alcohol was attached to the MeOPEG resin with an oxalyl chloride linkage (Scheme 11.23). Cycloaddition of alkynes with carbohydrate-derived azides gave resin-bound 1,2,3-triazoles, and reductive cleavage with sodium borohydride released the products as primary alcohols. 

Figure 7.12 Top a plausible mechanism for aliphatic hydroxylation involving insertion of electron-deficient oxygen into a C-H o bond. Bottom the sedative alprazolam undergoes aliphatic hydroxylation at two a-positions. The methyl group is oxidized to a primary alcohol, while the 4-position, which is a- with respect to the triazole ring and the imine, is oxidized to a secondary alcohol.

In 2012, Song Cao et al. devised a novel, one-pot, three-component approach for the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles 37 through the cycloaddition of a wide range of primary alcohols 36 with sodium azide and active methylene ketones 22 at 80 °C in the presence of Af-(p-toluenesulfonyl)imidazole (Tslm), tetrabutylammonium iodide (TBAl), and triethylamine (TEA) in DMF/DMSO (Scheme 4.12) [15]. Potassium hydroxide was used as the base for inducing the cycloaddition. The mild reaction conditions, high yields, and one-pot reaction without the necessity to isolate the unstable and hazardous... 

Scheme 4.12 One-pot, three-component synthesis of 1,4,5-trisubstituted 1,2,3-triazoles starting from primary alcohols.

The selectivity of the commercially available l,3,4-triphenyl-4,5-dihydro-lH-l,2-triazol-5-ylidene carbene 1 (Figure 9.2) for the ROP of lactide prompted Coulem-bier and coworkers to investigate its reactivity in the ROP of BL [76]. The group showed that, when the polymerization of BL was initiated from primary alcohol and 1 at 80 °C in toluene, the expected polymer chains were contaminated with crotonate byproducts. 

Kinetic analysis of the polymerization revealed a first-order dependence on monomer, triazole carbene and alcohol when [triazolej/falcohol] = 1, operating by a mechanism comparable to that proposed previously (Scheme 14.9). However, altering the ratio of triazole to alcohol such that [triazole]/[alcohol] > 1 resulted in the observation of a nonlinear dependence of rate on [triazole], and suggesting that a second pathway for lactide enchainment had become significant [28]. The authors proposed that, at high [triazole]/[alcohol] ratios, the direct addition of lactide to the zwitterionic intermediate Z (Scheme 14.9, path D) was able to compete with proton transfer (Scheme 14.9, path B). Further confirmation of the presence of competing mechanisms was obtained by analysis of an unquenched polymerization sample by electrospray ionization mass spectrometry (ESl-MS), in which the primary peaks were attributed to triazole end-capped polymers, while minor f)eaks were observed for both hydroxyl-terminated and macrocyclic PLAs. 

Under microwave irradiation and applying MCM-41-immobilized nano-iron oxide higher activity is observed [148]. In this case also, primary aliphatic alcohols could be oxidized. The TON for the selective oxidation of 1-octanol to 1-octanal reached to 46 with 99% selectivity. Hou and coworkers reported in 2006 an iron coordination polymer [Fe(fcz)2Cl2]-2CH30H with fez = l-(2,4-difluorophenyl)-l,l-bis[(l//-l,2,4-triazol-l-yl)methyl]ethanol which catalyzed the oxidation of benzyl alcohol to benzaldehyde with hydrogen peroxide as oxidant in 87% yield and up to 100% selectivity [149]. An alternative approach is based on the use of heteropoly acids, whereby the incorporation of vanadium and iron into a molybdo-phosphoric acid catalyst led to high yields for the oxidation of various alcohols (up to 94%) with molecular oxygen [150]. 

DiazotriazoIe 28 (R = Ph) reacted with /-butyl alcohol and 2-propanol to give compounds 148 and 149 (Scheme 40) in comparable yields by carbenic C—H insertion and nucleophilic substitution, respectively [81DIS(B)(42)1892]. In the case of 2-propanol, an oxidation-reduction process, to give the parent triazole and acetone, was also observed to a smaller extent. Also, it was previously reported that 3-diazotriazole 28 (R = COOH) oxidizes primary and secondary alcohols to the corresponding aldehydes and ketones (1898LA33). 

A Sandmeyer reaction leading to the 3-chloro derivatives was observed upon treatment of 3-diazotriazoles with aqueous hydrochloric acid [1898LA33 26JCS1729 78ZN(B)216]. 3-Diazotriazole was reduced to the parent triazole by treatment at 0°C with primary and secondary alcohols [86DIS(B) (46) 3052]. The mechanism is not clear, but the process may be envisaged as involving hydride transfer from the intermediate 244 obtained by nucleophilic addition of alcohols to the diazo compound (Scheme 70). 

In addition to alcohols, the same triazole carbene was employed in the presence of primary amino-containing precursors serving as initiators.In this case, however, the primary amino-function was shown to act as a bifunctional initiating... 

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