Protonated acetic alcohol

G Addition of a second equivalent of alcohol gives a protonated acetal. 

Wender and coworkers conclude that cobalt-catalyzed benzyl alcohol homologation involves the intermediate formation of car-bonium ions (8). However, since the methyl cation (CH3+) is unstable and difficult to form (9), it is more likely that methanol homologation to ethanol proceeds via nucleophilic attack on a protonated methyl alcohol molecule. Protonated dimethyl ether and methyl acetate forms have been invoked also by Braca (10), along with the subsequent formation of methyl-ruthenium moieties, to describe ruthenium catalyzed homologation to ethyl acetate. 

Tiedemann and Riveros (1974) first discussed the gas-phase reactions which are equivalent to an esterification reaction. An icr study of alcohols and acetic acid revealed that the formation of protonated acetic acid by ion-molecule reactions of fragment ions with acetic acid is followed by the rapid reaction (72). 

These considerations can be formulated by schemes (e)—(g) below (R1 = H or alkyl). Scheme (e), in which the acid (ester) is protonated and alcohol reacts in non-adsorbed state, corresponds to the mechanisms Aac1 or Aac2 proposed for homogeneous esterification and hydrolysis with ion exchanger catalysts, the mechanism (e) was assumed to be operating in the liquid phase esterification of salicyclic acid with methanol [449] and in the transesterification of ethyl acetate with the same alcohol in dioxan as... 

Hydrolysis of 63 in concentrated hydrochloric acid at 100 °C for 6 h afforded 95% of uracil diol 65 with H and 13C NMR spectral data virtually identical to those of cylindrospermopsin except for the protons and carbons close to C12. A similar hydrolysis of 64 provided 95% of 66. This hydrolysis is perhaps the most remarkable step in the synthesis. Very harsh conditions are needed to hydrolyze the dimethoxypyrimidine to the uracil. However, the reaction is remarkably clean, accompanied only by the desired hydrolysis of the acetate ester, but no decomposition or epimerization at any of the stereocenters. Presumably, the protonated guanidine and uracil make it hard to protonate either alcohol and solvolyze to form a trication. 

A second molecule of alcohol attacks the carbonyl carbon that is forming the protonated acetal. 

The presence of two heteroatoms complicates the mechanism. In fact, propyl acetate yields protonated acetic acid as a base peak, whereas methylbutyrate yields an (RCOOH + H)+ peak that is hardly detectable the proton is derived from the alcohol. Experiments on propyl acetate labelled with deuterium at various positions on the propyl chain yield the following percentages concerning the origin of the proton during the rearrangement. This distribution seems fairly statistical ... 

The reaction involves the formation (step I) of the ion I, which then combines (step 2) with a molecule of alcohol to yield the protonated acetal. As we can see,... 

A protonated compound is a compound that has gained an additional proton. A pro-tonated alcohol or a protonated carboxylic acid is a very strong acid. For example, protonated methanol has a of -2.5, protonated ethanol has a pK of -2.4, and protonated acetic acid has a pK of -6.1. 

The nonsteric interactions in ipc depend on the chemical structure of the analyte, and also on nature of stationary and mobile phases. In normal- or reversed-phase hplc, neutral solutes are separated on the basis of their polarity. In the former case, polar stationary phases are employed (eg, bare sihca with polar silanol groups) and less polar mobile phases based on nonpolar hydrocarbons are used for elution of the analytes. Solvent selectivity is controlled by adding a small amoimt of a more polar solvent, such as 2-propanol or acetonitrile or other additives with large dipole moments (methylene chloride and 1,2-dichloroethane), proton donors (chloroform, ethyl acetate, and water), or proton acceptors (alcohols, ethers, and amines). Correspondingly, the more polar the solute, the greater is its retention on the column, yet increasing the polarity of the mobile phase results in decreased solute retention. 

The mechanism for the acid-catalyzed conversion of a hemiacetal to an acetal is divided into four steps. As you study this mechanism, note that acid is a true catalyst in this reaction. The protonated alcohol is used to add a proton in Step 1, but another proton-ated alcohol is generated in Step 4. The latter steps of this mechanism are very similar to those for hemiacetal formation. 

Step 4 Take a proton away. Proton transfer from the protonated acetal to alcohol gives the acetal and generates a new molecule of the acid catalyst. 

Protonated alcohols and protonated carboxylic acids are very strong acids. For example, protonated methyl alcohol has a p Ta of —2.5, protonated ethyl alcohol has a p Ta of —2.4, and protonated acetic acid has a p Ta of—6.1. 

Structural effects can now be discussed by asking how they will affect the position of the transition state on the potential energy surface. The stepwise path via the protonated acetal should be followed in the case of alcohols that are poor... 

As shown in Figure 19.10, nucleophilic addition of an alcohol to the carbonyl group initially yields a hydroxy ether called a hemiacetal, analogous to the gem diol formed by addition of water. Hemiacetals are formed reversibly, with the equilibrium normally favoring the carbonyl compound. In the presence of acid, however, a further reaction occurs. Protonation of the -OH group, followed by an El-like loss of water, leads to an oxonium ion, R2C=OR", which undergoes a second nucleophilic addition of alcohol to yield the protonated acetal. Loss of a proton completes the reaction. 

The carbocation reacts with the alcohol in another reaction to give a protonated acetal. 

Acid—Base Chemistry. Acetic acid dissociates in water, pK = 4.76 at 25°C. It is a mild acid which can be used for analysis of bases too weak to detect in water (26). It readily neutralizes the ordinary hydroxides of the alkaU metals and the alkaline earths to form the corresponding acetates. When the cmde material pyroligneous acid is neutralized with limestone or magnesia the commercial acetate of lime or acetate of magnesia is obtained (7). Acetic acid accepts protons only from the strongest acids such as nitric acid and sulfuric acid. Other acids exhibit very powerful, superacid properties in acetic acid solutions and are thus useful catalysts for esterifications of olefins and alcohols (27). Nitrations conducted in acetic acid solvent are effected because of the formation of the nitronium ion, NO Hexamethylenetetramine [100-97-0] may be nitrated in acetic acid solvent to yield the explosive cycl o trim ethyl en etrin itram in e [121 -82-4] also known as cyclonit or RDX. 

Acidic Cation-Exchange Resins. Brmnsted acid catalytic activity is responsible for the successful use of acidic cation-exchange resins, which are also soHd acids. Cation-exchange catalysts are used in esterification, acetal synthesis, ester alcoholysis, acetal alcoholysis, alcohol dehydration, ester hydrolysis, and sucrose inversion. The soHd acid type permits simplified procedures when high boiling and viscous compounds are involved because the catalyst can be separated from the products by simple filtration. Unsaturated acids and alcohols that can polymerise in the presence of proton acids can thus be esterified directiy and without polymerisation. 

The initiating step in these reactions is the attachment of a group to the sulfoxide oxygen to produce an activated intermediate (5). Suitable groups are proton, acyl, alkyl, or almost any of the groups that also initiate the oxidations of alcohols with DMSO (40,48). In a reaction, eg, the one between DMSO and acetic anhydride, the second step is removal of a proton from an a-carbon to give an yUde (6). Release of an acetate ion generates the sulfur-stabilized carbonium ion (7), and the addition of acetate ion to the carbonium ion (7) results in the product (eq. 15) ... 

The poly(vinyl alcohol) made for commercial acetalization processes is atactic and a mixture of cis- and /n j -l,3-dioxane stereoisomers is formed during acetalization. The precise cis/trans ratio depends strongly on process kinetics (16,17) and small quantities of other system components (23). During formylation of poly(vinyl alcohol), for example, i j -acetalization is more rapid than /ra/ j -acetalization (24). In addition, the rate of hydrolysis of the trans-2iQ. -A is faster than for the <7 -acetal (25). Because hydrolysis competes with acetalization during acetal synthesis, a high cis/trans ratio is favored. The stereochemistry of PVF and PVB resins has been studied by proton and carbon nmr spectroscopy (26—29). 

Aromatic ethers and furans undergo alkoxylation by addition upon electrolysis in an alcohol containing a suitable electrolyte.Other compounds such as aromatic hydrocarbons, alkenes, A -alkyl amides, and ethers lead to alkoxylated products by substitution. Two mechanisms for these electrochemical alkoxylations are currently discussed. The first one consists of direct oxidation of the substrate to give the radical cation which reacts with the alcohol, followed by reoxidation of the intermediate radical and either alcoholysis or elimination of a proton to the final product. In the second mechanism the primary step is the oxidation of the alcoholate to give an alkoxyl radical which then reacts with the substrate, the consequent steps then being the same as above. The formation of quinone acetals in particular seems to proceed via the second mechanism. ... 

In solvents containing low concentrations of water in acetic acid, dioxane, or sulfolane, most of the alcohol is formed by capture of water with retention of configuradon. This result has been explained as involving a solvent-separated ion pair which would arise as a result of concerted protonation and nitrogen elimination. ... 

Metal-ammonia solutions reduce conjugated enones to saturated ketones and reductively cleave a-acetoxy ketones i.e. ketol acetates) to the unsubstituted ketones. In both cases the actual reduction product is the enolate salt of a saturated ketone this salt resists further reduction. If an alcohol is present in the reaction mixture, the enolate salt protonates and the resulting ketone is reduced further to a saturated alcohol. Linearly or cross-conjugated dienones are reduced to enones in the absence of a proton donor other than ammonia. The Birch reduction of unsaturated ketones to saturated alcohols was first reported by Wilds and Nelson using lithium as the reducing agent. This metal has been used almost exclusively by subsequent workers for the reduction of both unsaturated and saturated ketones. Calcium has been preferred for the reductive cleavage of ketol acetates. 

Much information on proton transfers has been obtained by NMR chemical exchange studies. An example is the proton exchange between neopentyl alcohol and acetic acid in acetic acid as the solvent. The reaction is... 

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