Pyridine reactions with alcohols

Aryl(trimethylsiloxy)carbenes. Acylsilanes (153) undergo a photoinduced C —> O silyl shift leading to aryl(trimethylsiloxy)carbenes (154).73,74 The carbenes 154 can be captured by alcohols to form acetals (157) 73 or by pyridine to give transient ylides (Scheme 29).75 LFP of 153 in TFE produced transient absorptions of the carbocations 155 which were characterized by their reactions with nucleophiles.76 The cations 155 are more reactive than ArPhCH+, but only by factors < 10. Comparison of 154 and 155 with Ar(RO)C and Ar(RO)CH+, respectively, would be of interest. Although LFP was applied to generate methoxy(phenyl)carbene and to monitor its reaction with alcohols,77 no attempt was made to detect the analogous carbocation. 

Hydroxypyridines are readily alkylated under a variety of conditions. Mitsunobu reaction with alcohols occurs selectively at oxygen in the presence of PPh3 and DEAD in THF at room temperature <2003TL725>. The 3-hydroxy group may be selectively alkylated in the presence of aliphatic hydroxyl groups. Pyridine 104 is alkylated at the aromatic position with dodecyl bromide in the presence of potassium carbonate in DMF at 95 °C <20030BC644> (Equation 70). 

Selenium tetrafluoride, which can be prepared from selenium metal and chlorine trifluoridc (CIF3), was introduced by Olah as a fluorinating agent for carbonyl compounds and alcoholsT It is generally necessary to add pyridine in the reactions with alcohols I. Pyridine forms a I 1 complex with selenium tetrafluoride and neutralizes the hydrogen fluoride which is formed in the fluorination reaction. 

Considerable research has been reported on the third process which Involves reaction of pyridine compounds with alcohols or potential alcohols in the presence of various nickel catalysts. 

The sulfamoyl esters (102) and (103) are prepared by condensation of the corresponding sulfamoyl halides (104) and (105) with the appropriate alcohol, alkoxide, phenol or phenoxide a suitable base, e.g. pyridine, is needed for the reaction with alcohols (Scheme 44). The yields of the sulfamoyl esters are often poor but... 

MeS02Cl, pyridine, 0°C, 65-83% yield." Although the yields are moderate compared to more conventional methods, this reaction is important in that these conditions are often used to prepare mesylates of alcohols which indicates that some caution must be exercised with free acids during reactions with alcohols. 

At ambient temperature, capture by pyridine was fast (7.9 x 10"M- s- ), as was reaction with alcohols. Plots of kohs against alcohol concentration (at constant [Py]) were not linear, as hydrogen-bonded oligomeric aggregates reacted faster than monomeric alcohols. From the four alcohols studied, it is possible to derive a very approximate Bronsted a of 0.4 for the reaction with monomeric alcohols, with the rate for hexafluoro-2-propanol (2.9 x 10 M-... 

Reaction with alcohols (Section 15.8) Acyi chiorides react with aicohois to form esters. The reaction is typicaiiy carried out in the presence of pyridine. 

Reaction with alcohols (Section 15.8) Acid anhydrides react with alcohols to form esters. The reaction may be carried out in the presence of pyridine or it may be catalyzed by acids. In the example shown, only one acetyl group of acetic anhydride becomes incorporated into the ester the other becomes the acetyl group of an acetic acid molecule. 

The great significance of the later discovery, that exactly comparable additions to iV-aUcoxycarbonyl- or iV-aryloxycarbonyl-pyridinium cations, generated and reacted in situ, is that the dihydro-pyridines that resnlt are stable, and can be further manipulated. If re-aromatisation " is required, the iV-substituent can be easily removed to give a substituted pyridine. It is worth noting the contrast to the use of A-acyl-pyridinium salts for reaction with alcohol, amine nncleophiles (8.1.1.7), when attack is at the carbonyl carbon the nse of an iV-alkoxy/aryloxycarbonyl-pyridininm salt in the present context diverts attack to a ring carbon. 

The reaction of [l,2,3]diazaphospholo[l,5-a]pyridine (22) with alcohol is completed only in the presence of sulfur or selenium and a catalytic amount of the respective sodium alkoxide to give 66. The reaction with thiophenol also occurs in the presence of sulfur to form 67 however no catalyst is required in this case (Scheme 24) [78],... 

Reaction with Alcohols and Phenols. The reaction of alcohols and phenols with triflic anhydride (Tf20) at 0°C in the presence of a base (usually Pyridine) in an inert solvent (usually dichloromethane) for 2-24 h affords the corresponding reactive trifluoromethanesulfonate esters (triflates). When triflic anhydride and pyridine are combined, the pyridinium salt forms immediately and normally precipitates out from the reaction mixture. Nevertheless, the salt is an effective esterifying agent, reacting with the added alcohol to give triflates in high yields (eq 1). ... 

Most metal chlorides undergo only partial metathetical halide/alkoxide exchange upon reaction with alcohols or no reaction at all even at elevated temperatures. The metal alkoxide chlorides thus obtained, MClx(OR), have not been used in sol-gel processing (see, however. Section 7.10.3.3.2). In order to achieve the preparation of homoleptic metal alkoxides from metal chlorides basic conditions are essential in order to trap the liberated HCl. This can be achieved by reaction of metal chlorides with alcohols in the presence of a base such as ammonia or, less often, trialkylamines or pyridine (Equation (11a)). The base also increases the equilibrium concentration of alkoxide ions, which are a more powerful nucleophile for reaction with the metal chloride than the parent alcohol. For this reason the use of alkali alkoxides (M OR), mostly lithium, sodium, or potassium alkoxides, proves to be more successful (Equation (11b)). The use of LiOR has advantages for the preparation of insoluble metal methoxides because LiCl is soluble in methanol and is thus easily separated from insoluble metal alkoxides. 

The cyclization of ort/zo-allyl phenols was reported by Murahashi in the late 1970s. The reaction of the 2-(2-cyclohexenyl)phenol (Equation 16.110) was one of the early examples of Wacker-type reactions with alcohol nucleophiles and has been re-investigated in more recent years with chiral catalysts. Intramolecular reactions of alkene-ols and alkenoic acids form cyclic ethers and lactones. These reactions were reported by Larock and by Annby, Andersson, and co-workers, and examples are shown in Equations 16.111 and 16.112. °° ° The use of DMSO as solvent was important to form the lactone products. More recently, reactions with alcohols were reported by Stoltz to form cyclic ethers by the use of pyridine and related ligands in toluene solvent. - The type of ligand, whether an additive or the solvent, is crucial to the development of these oxidative processes. However, the features of these ligands that lead to catalysis are not well understood at this time. 

Pyridine-carboxylic acid chlorides, usually prepared by the use of thionyl chloride [a reaction in which nuclear chlorination sometimes occurs (p. 227)], are in most respects normal though rather unstable. Their reactions with alcohols provide some of the best ester preparations in this series. The Rosen-mund reduction fails with all three of the pyridoyl chlorides i though it... 

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