Pyridyl -2-propanol

This procedure is based upon that of Ziegler.2 l-(a-Pyridyl)-2-propanol has also been prepared in poor yields (4-6 per cent) by heating a-picoline with aqueous acetaldehyde in sealed tubes.3-4... 

The chlorine atom in 4-chloropyridine can be replaced photochemically by the dimethyl ketyl radical755. Irradiation of 4-chloropyridine in a 4 1 mixture of 2-propanol and water gives a low yield (2%) of 2-(4 -pyridyl)-2-propanol. Sensitization by benzophenone increases the yield to 25%, but the product is now accompanied by 6% of diphenyl-(4-pyridyl)methanol. The major product is believed to be formed via hydrogen abstraction from 2-propanol by photoexcited pyridine. Protonated pyridines do not undergo this abstraction process, and accordingly the product yield decreases under acidic conditions. The radical (259) formed from the pyridine will combine (at position 4) with the dimethyl ketyl radical (260) and elimination of HC1 from the adduct (261) completes the reaction (equation 194). 

To 9 g of n-butyllithium in 200 ml of dry ether 20 g of 3-bromopyridine Is added as quickly as possible at -40°C without raising the temperature. When the addition Is finished the mixture is stirred for another 30 minutes. Thereafter 32.5 g of 0>dimethylamino-4 -bromopro-piophenone is added in such a way that the temperature does not exceed -40°C. The cooling is discontinued and the mixture is stirred during the night whereupon the reaction mixture is poured onto ice and diluted HCI, which is washed with ether and is extracted with 20 ml of methylene dichloride. The methylene dichloride is dried and evaporated. The crystals are dissolved in water, which then is made alkaline with a solution of Na2C03, is extracted with ether, dried, and evaporated and recrystallized from isopropyl ether, petroleum ether 1 1. Yield 4 g of 1 -(4 -bromophenyl)-3-(N,N-dimethylamino)-1 -(3"-pyridyl)-propanol. Melting point 67°C. 

Sodium borohydride, even in a very large excess, reduced methyl 2-none-noate and methyl cinnamate incompletely to mixtures of saturated esters, unsaturated alcohols and saturated alcohols [1061]. On the other hand, a,p-unsaturated esters of pyridine and pyrimidine series were converted predominantly and even exclusively to saturated alcohols. Methyl 3-(7-pyri-dyl)acrylate gave, on refluxing for 1-2 hours in methanol with 10 mol of sodium hydride per mol of the ester, 67% of 3-(y-pyridyl)propanol and 6% of 3-(y-pyridyl)-2-propenol methyl 3-(6-pyrimidyl)acrylate gave 77% of pure 3-(6-pyrimidyl)propanol [1061]. 

The most favourable route to indolizine itself is a one-step cyclization of 3-(2-pyridyl)-propanol (134a) (59JA1456). A second route, which involves the reaction of 2-pyridyllithium with epichlorohydrin (69CB1309), has been found to proceed in varying yields. Compound... 

When 2-pyridinecarboxaldehyde is added to a cooled solution of nitroethane and diethylamine in ethanol, 2-nitro-l-(2-pyridyl)propanol (IX-280) is obtained. Dehydration of IX-280 followed by hydrogenation gives... 

Molecular arrangements in the as-prepared dimer and 2 OPr-a-dimer-PrOH crystals are shown schematically in Figs 16(a) and (b), respectively. In the complex, propanol molecules are hydrogen-bonded to the pyridyl groups and, as expected from its high photoreactivity, the... 

Equally good yields of l-(a-pyridyl)-3-propanol, b.p. 116— 118°/4 mm., may be obtained by using ethylene oxide in place of acetaldehyde. 

The carbonylation of the sp3 C-H bond adjacent to a nitrogen atom is also possible by means of chelation-assisted C-H bond activation.121 The carbonylation reaction of A-(2-pyridyl)pyrrolidine occurs at the a-position of the pyrrolidine ring by using [RhCl(cod)]2 as a catalyst and 2-propanol as a solvent. Cyclic amines exhibit a high reactivity (up to 84%) (Equation (93)), while acyclic amines show relatively low reactivity (18%). The use of Ru3(CO)i2 as a catalyst does not result in a carbonylation reaction, but instead the addition of the sp3 C-H bond across the olefin bond to give an alkylation product, as mentioned before (Section 10.05.4). 

In the course of the continuing study [9a,b] on the enantioselective addition of dialkylzincs to aldehydes by using chiral amino alcohols such as diphenyl(l-methyl-2-pyrrolidinyl)methanol (45) (DPMPM) [48] A. A -dibutylnorephedrine 46 (DBNE) [49], and 2-pyrrolidinyl-l-phenyl-1-propanol (47) [50] as chiral catalysts, Soai et al. reacted pyridine-3-carbaldehyde (48) with dialkylzincs using (lS,2/ )-DBNE 46, which gave the corresponding chiral pyridyl alkanols 49 with 74-86% ee (Scheme 9.24) [51]. The reaction with aldehyde 48 proceeded more rapidly (1 h) than that with benzaldehyde (16 h), which indicates that the product (zinc alkoxide of pyridyl alkanol) also catalyzes the reaction to produce itself. This observation led them to search for an asymmetric autocatalysis by using chiral pyridyl alkanol. 

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