Primaiy alcohols

This group is prepared by the reaction of the anion of 9-hydroxyanthracene and the tosylate of an alcohol. Since the formation of this group requires an S 2 displacement on the alcohol to be protected, it is best suited for primaiy alcohols. It is cleaved by a novel singlet oxygen reaction followed by reduction of the endo-peroxide with hydrogen and Raney nickel. 

Bu2SnO, PhCH3, heat, 10 h with H2O removal, then Bu4N Br , TBDPSCl, heat, 8 h. This method was used to introduce one TBDPS group on one of two primaiy alcohols in 92% yield. 

In cases where two 1,2-acetonides are possible, the thermodynamically favored one prevails. Secondaiy alcohols have a greater tendency to form cyclic acetals than do primaiy alcohols,but an acetonide from a primaiy alcohol is preferred over an acetonide from two trans, secondaiy alcohols. 

It is important to note that although methyl and primaiy alcohols react with hydrogen halides by a mechanism that involves fewer steps than the conesponding reactions of secondary and tertiary alcohols, fewer steps do not translate to faster reaction rates. Remember, the order of reactivity of alcohols with hydrogen halides is tertiary > secondary > primary > methyl. Reaction rate is governed by the activation energy of the slowest step, regardless of how many steps there are. 

As noted eaiTier (Section 4.10) primary caibocations aie too high in energy to be intennediates in most chemical reactions. If primaiy alcohols don t fonn primary caibocations, then how do they undergo elimination A modification of our general mechanism for alcohol dehydration offers a reasonable explanation. For primary alcohols it is... 

Conditions that do pennit the easy isolation of aldehydes in good yield by oxidation of primaiy alcohols employ vaiious Cr(VI) species as the oxidant in anhydrous media. Two such reagents ar e pyridinium chlorochromate (PCC), C5H5NH ClCi03, and pyridinium dichromate (PDC), (C5H5NH)2 Ci207 both are used in dichloromethane. 

Secondary alcohols are oxidized to ketones by the sane reagents that oxidize primaiy alcohols ... 

Transesterification is catalyzed by acids or bases, or performed under neutral conditions. It is an equilibrium reaction and must be shifted in the desired direction. In many cases, low-boiling esters can be converted to higher boiling ones by the distillation of the lower boiling alcohol as fast as it is formed. Reagents used to catalyze transesterification include In/l2, Montmorillonite KlOclay, Ti(OEt)4, Cu(N03)2, which with ethyl acetate is elective for primaiy alcohols, ... 

Carboxylic acids are reduced to primaiy alcohols by lithium aluminium hydride or better with diborane. Diborane does not easily... 

Ac20, Pyr, 20°, 12 h, 100% yield.1 This is one of the most common methods for acetate introduction. By running the reaction at lower temperatures good selectivity, pan be achieved for primaiy alcohols over secondaiy alcohols.2 Tertiary alcohols are generally not acylated under these conditions. 

Strategy " What 15 an immediate precursor of a primaiy alcohol Perhaps an AlkenCt which could be hydrated with non-Markovntkov regiochemiato by reaction with boranc followed hy oxidaiion with H2O2 ... 

Figure 14. A sketch of the H-bond dynamics for primaiy alcohols with long alkylic chains. fi, mole fraction with i intact hydrogen bonds ( ) intact hydrogen bond (O) broken hydrogen bond. ( 1.2) k +i-(2-f)/3Ty (i-0,1).

In the presence of a trace of an alkaline catalyst, a 3-hydroxy-propionate ester is formed in a good yield as the reaction with tlic primaiy alcohols is very rapid, it is advantageous to run the reaction at a low temperature with excess of alcohol to cut down the polymerization. This is difficult to avsecondary alcohols which, therefore, give rather low yields of hydraerylic estw. 

Many reagents known for the direct conversion of alcohols into halides have been used to achieve site-selective nucleophilic substitution in polyhydroxy compounds [44-46,62]. In some cases, it is possible to effect selective displacements of primaiy alcohols in the presence of secondary ones, and to achieve differential substitutions of secondary alcohols in unprotected sugars [44,45,64,65] (Scheme 4). 

It was found that the signs of rotation of the recovered a-phenyl-butyrio acid corresponded to the known absolute configurations of the deuteriated alcohols if and only if the size relationships CH3 > CfDs and H>D were valid. In the case of ( + )-(S)-2-propanol-l,l,l-ds (4), the optical yield was between 0-4 and 0-5% (Horeau et al., 1965), corresponding to a A AG value of about 23 cal mol at 26°C. For the primaiy alcohols, quite analogous results were obtained (Horeau and Nouaille, 1966). 

The answer is D. Primaiy alcohols are more acidic than secondary alcohols, and secondary alcohols are more acidic than tertiary alcohols. Ammonia is much weaker than any other compound in the remaining choices. In fact NHj has a pKa of roughly 36. All the alcohols listed have pKa values ranging from 16 through 18. 

Alcohol has probability 0.9 Primaiy alcohol has probability 0.01 Secondaiy alcohol has probability 0.99 Tertiaiy alcohol has probability 0.01 Phenol has probability 0.01... 

In addition to kinetic resolution processes, the previously described peptide-catalysed acylation reaction of alcohols can be applied to desymmetrisation of meso compounds. In 2005, Miller and coworkers published the desymmetrisation of prochiral glycerol derivatives via enantioselective acylation of one primaiy alcohol function. A (3-tum histidine-based pentapeptide was identified as the most promising catalyst from a peptide libraiy and afforded the monoacylated product with up to 97% enantiomeric excess. One year later Miller and Hansen successfully demonstrated the desymmetrisation of a meso bis-phenol compound, which was found to be challenging because of the large distance between the two OH groups as well as between the desired site of functionalisation and the prochiral stereogenic centre of the substrate. The nucleophilic N-methylhistidine containing peptide 9 was identified as a powerful tool for monoacylation via extensive libraiy... 

Primaiy alcohols can be oxidized to aldehydes and carboxylic acids. Often it is difficult to stop at the aldehyde... 

A specific oxidizing agent for the conversion of primaiy alcohols to aldehydes is pyridinium chlorochromate, abbreviated as py CrOsCl A Generally, the oxidation is run in methylene chloride solvent. For example. 

Primaiy Alcohols. Reaction 13.8 gives the general reaction, and the formation of acetic acid Is a specific example (Reaction 13.9) ... 

Primaiy alcohols with extensive jS-branching give large amounts of a product derived from rearrangement. For example, treatment of 2,2-dimethyl-l-propanol (neopentyl alcohol) with HBr gives a rearranged product almost exclusively. 

Shown in Figure 12.8 is an infrared spectrum of neat 1-hexanol. The hydrogen-bonded O—H stretching appears as a broad band of strong intensity centered at 3340 cm T The C—O stretching appears at 1058 cm a value characteristic of Figure 12 8 primaiy alcohols. of 1-hexanol... 

Galactose oxidase (GO) is a mononuclear radical-coupled copper enzyme which catalyzes the oxidation of primary alcohols using molecular oxygen, producing aldehydes and H2O2. Galactose oxidase can be present in three oxidative states (6,7) The active oxidized form with a tyrosine radical in the active site, the reduced form which results from the two electron redox reaction by which a primaiy alcohol is converted to an aldehyde (Cu, tyrosine), and an intermediate semi-form containing tyrosine. The three oxidation states can be defined as in equation I. 

Scheme 8.45 Enz5nnatic DKR of primaiy alcohols with Shvo s catatyst.

Scheme 8.46 Enzymatic DKR of primaiy alcohols derived from tropic acid ethyl ester with Shvo s catalyst.

C aibo lic acids Hydio Qr fi-ketone Primaiy alcohols Secondaiy alcohols B-diketone Esters... 

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