The alcohol have been applied in methylene chloride as inert solvent. The tested nitriles are acetonitrile, benzyl cyanide, benzonitrile, and acrylonitrile (Table 2). Best yields were obtained inside the reactions of major alcohols with acetonitrile and benzyl cyanide (Table two, entries 1). Somewhat reduced yields were observed with acrylonitrile; nonetheless, reported solutions for the preparation of acrylate 5 cause similar, and in some instances even lower yields [13,14]. A typical protocol for the synthesis of 9H-fluoren-9-ylmethyl acrylate starting with all the moisture-sensitive acryloyl chloride below an inert atmosphere was reported to yield only 33 [15]. TheBeilstein J. Org. Chem. 2013, 9, 1572577.Table 2: Variation of nitriles and alcohols.a# R2-OH 1 2 three 4 5 6 7 eight 9 ten 11 (48) 12 13 14aAlcohol cTMSOTfR1 = Me Item, Yield [ ] two, 83 7, 80 12, 84 17, 75 22, 90 27, 88 32, 32 (33, 19c) 37, 21 42, 13 46, 15 0 PhOH (49) p-NO2C6H4OH (50) 3,4,5-Trimethoxyphenol (51) p-MeOC6H4CH2OH (52) 0 0 0R1 = BnR1 = PhR1 = VinylFluorenylmethanol (1) Me(CH2)9OH (6) Cl(CH2)6OH (11) Et[O(CH2)2]2OH (16) p-NO2C6H4CH2OH (21) p-HO2CC6H4CH2OH (26) HO(CH2)6OH (31) EtO2C(CH2)5OH (36) Z-NH(CH2)4OH (41) cyHexOH (45)3, 86 8, 85 13, 90 18, 85 23, 78 28, 87 34, 46 (35, 37c) 38, 16 43, 13 47, 25 0 — — –4, 44 9, 23 14, 27 19, 26 24, 39 29, 31 — 39, 10 0 — — — — –5, 52 (67b) 10, 29 (40b) 15, 38 (16b) 20, 23 (19b) 25, 85 30, 64 — 40, 7 44, 14 — — — — –(1 equiv), TMSOTf (2 equiv) dissolved within the nitrile (four mL/mmol alcohol), rt, 65 h. bTMSOTf (two equiv) and nitrobenzene (1 equiv) were added. (4 equiv) was added. Yield in the monoacylated by-products 33 and 35, respectively, in parentheses.with acetonitrile and benzyl cyanide, respectively (Scheme six). The respective esters 54 and 55 were obtained with superior yields: no esterification on the phenolic hydroxy group was observed. The reaction of 4-(2-hydroxyethyl)phenol (53) with benzyl cyanide yielded monaspilosin (55), an aromatic ester isolated in the mould fungus Monascus pilosus by Cheng et al. [18]. This compound was reported to have radical scavenger properties. The first total synthesis of this organic solution was herewith accomplished with 73 yield in only one step. Good yields were observed, when benzyl alcohols with electron withdrawing (-M) substituents such as 4-nitrobenzyl alcohol (21, Table 2, entry five) and 4-hydroxymethylbenzoic acid (26, Table 2, entry 6) had been reacted with benzyl cyanide or acetonitrile and even with acrylonitrile. A protection of the carboxylic acid turned out to be not necessary. In contrast, a TLR2 Agonist supplier 4-methoxy-substituted benzyl alcohol 52, i.e., an electron-rich benzyl alcohol, furnished no carboxylic ester at all (Table 2, entry 15). Rather poor yields of the respective carboxylic esters had been achieved, when unsubstituted benzyl alcohol (56) or 4-fluorobenzyl alcohol (64) had been reacted with one of several carbonitriles (Table 3). Instead we isolated substantial amounts of carboxamides. These amides PDE9 Inhibitor list result from a Ritter-type reaction [19-21], where a carbenium ion (or perhaps a substrate with signifi-Scheme six: Synthesis of monaspilosin.cant positive partial charge) reacts at the nitrogen atom of a nitrile. This transformation is usually a competitors towards the Pinner reaction, when benzyl alcohols are utilised. A probable mechanism of this reaction is offered in Scheme 7. Double silylation results in the formation of an excellent leaving group plus the highly electrophilic benzylic carbon is attacked by the nitrile yielding a nitrilium c.