Hemiacetal cyclic

To solve this problem we can use a protecting group to block the more reactive ketone carbonyl group. The overall process requires three steps. 

The following three-step sequence using a cyclic acetal leads to the desired product. 

Problem 21.37 How would you use a protecting group to carry out the following transformation  

Although acyclic hemiacetals are generally unstable and therefore not present in appreciable amounts at equilibrium, cyclic hemiacetals containing five- and six-membered rings are stable compounds that are readily isolated. 

All hemiacetals are formed by nucleophilic addition of a hydroxy group to a carbonyl group. In the same way, cyclic hemiacetals are formed by intramolecular cyclization of hydroxy aldehydes. 

Step [1] The ketone carbonyl is protected as a cychc acetal by reaction of the starting material with HOCH2CH2OH and TsOH. 

Step [2] Reduction of the ester is then carried out with LiAlHt, followed by treatment with 

Step [3] The acetal is then converted back to a ketone carbonyl group with aqueous acid. 

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Compounds that contain both carbonyl and alcohol functional groups are often more stable as cyclic hemiacetals or cyclic acetals than as open chain compounds Examples of several of these are shown Deduce the structure of the open chain form of each... 

Aldoses incorporate two functional groups C=0 and OH which are capable of react mg with each other We saw m Section 17 8 that nucleophilic addition of an alcohol function to a carbonyl group gives a hemiacetal When the hydroxyl and carbonyl groups are part of the same molecule a cyclic hemiacetal results as illustrated m Figure 25 3 Cyclic hemiacetal formation is most common when the ring that results is five or SIX membered Five membered cyclic hemiacetals of carbohydrates are called furanose forms SIX membered ones are called pyranose forms The nng carbon that is derived... 

FIGURE 25 3 Cyclic hemiacetal formation in 4 hydroxybutanal and 5 hydroxypentanal... 

Aldoses exist almost exclusively as their cyclic hemiacetals very little of the open chain form is present at equilibrium To understand their structures and chemical reac tions we need to be able to translate Fischer projections of carbohydrates into their cyclic hemiacetal forms Consider first cyclic hemiacetal formation m d erythrose To visualize furanose nng formation more clearly redraw the Fischer projection m a form more suited to cyclization being careful to maintain the stereochemistry at each chirality center... 

Structural drawings of carbohydrates of this type are called Haworth formulas, after the British chemist Sir Walter Norman Haworth (St Andrew s University and the University of Birmingham) Early m his career Haworth contributed to the discovery that carbohydrates exist as cyclic hemiacetals rather than m open chain forms Later he col laborated on an efficient synthesis of vitamin C from carbohydrate precursors This was the first chemical synthesis of a vitamin and provided an inexpensive route to its prepa ration on a commercial scale Haworth was a corecipient of the Nobel Prize for chem istry m 1937... 

During the discussion of hemiacetal formation in d ribose in the preceding section you may have noticed that aldopentoses have the potential of forming a six membered cyclic hemiacetal via addition of the C 5 hydroxyl to the carbonyl group This mode of ring closure leads to a and p pyranose forms... 

The anomeric carbon of a furanose or pyranose form of a ketose bears both a hydroxyl group and a carbon substituent In the case of 2 ketoses this substituent is a CH2OH group As with aldoses the anomeric carbon of a cyclic hemiacetal is readily identifi able because it is bonded to two oxygens... 

Although carbohydrates exist almost entirely as cyclic hemiacetals m aqueous solution they are m rapid equilibrium with their open chain forms and most of the reagents that react with simple aldehydes and ketones react m an analogous way with the carbonyl functional groups of carbohydrates... 

The carbonyl group of carbohydrates can be reduced to an alcohol function Typi cal procedures include catalytic hydrogenation and sodium borohydnde reduction Lithium aluminum hydride is not suitable because it is not compatible with the solvents (water alcohols) that are required to dissolve carbohydrates The products of carbohydrate reduc tion are called alditols Because these alditols lack a carbonyl group they are of course incapable of forming cyclic hemiacetals and exist exclusively m noncyclic forms... 

Carbohydrates are marvelous molecules In most of them every carbon bears a functional group and the nature of the functional groups changes as the molecule mterconverts between open chain and cyclic hemiacetal forms Any approach to understanding carbohydrates must begin with structure... 

Most carbohydrates exist as cyclic hemiacetals Those with five membered rings are called furanose forms those with six membered rings are called pyranose forms... 

Furanose form (Section 25 6) Five membered nng ansing via cyclic hemiacetal formation between the carbonyl group and a hydroxyl group of a carbohydrate... 

Ketoses, like aldoses, exist mainly as cyclic hemiacetals. In the case of D-ribulose, furanose forms result from addition of the C-5 hydroxyl to the car bonyl group. 

When this sequence is applied to carbohydrates, the first step takes place intramoleai-larly to yield a cyclic hemiacetal. The second step is intermolecular, requires an alcohol R"OH as a reactant, and proceeds readily only in the presence of an acid catalyst. An oxygen-stabilized carbocation is an intermediate. 

Acetal and hemiacetal groups are particularly common in carbohydrate chemistry. Glucose, for instance, is a polyhydroxy aldehyde that undergoes an internal nucleophilic addition reaction and exists primarily as a cyclic hemiacetal. 

Glycolysis is a ten-step process that begins with isomerization of glucose from its cyclic hemiacetal form to its open-chain aldehyde form—a reverse nucleophilic addition reaction. The aldehyde then undergoes tautomerixa-tion to yield an enol, which undergoes yet another tautomerization to give the ketone fructose. 

If the carbonyl and the hydroxyl group are in the same molecule, an intramolecular nucleophilic addition can take place, leading to the formation of a cyclic hemiacetal. Five- and six-membered cyclic hemiacetals are relatively strain-free and particularly stable, and many carbohydrates therefore exist in an equilibrium between open-chain and cyclic forms. Glucose, for instance, exists in aqueous solution primarily in the six-membered, pyranose form resulting from intramolecular nucleophilic addition of the -OH group at C5 to the Cl carbonyl group (Figure 25.4). The name pyranose is derived from pyran, the name of the unsaturated six-membered cyclic ether. 

Some monosaccharides also exist in a five-mem be red cyclic hemiacetal form called a furanose form. D-Fructose, for instance, exists in water solution as 70% /Tpvranose, 2% a-pyranose, 0.7% open-chain, 23% /3-furanose, and 5% a-furanose. The pyranose form results from addition of the -OH at C6 to the carbonyl group, while the furanose form results from addition of the —OH at C5 to the carbonyl group (Figure 25.5). 

Monosaccharides normally exist as cyclic hemiacetals rather than as open-chain aldehydes or ketones. The hemiacetal linkage results from reaction of the carbonyl group with an —OH group three or four carbon atoms away. A... 

Towards the end of the nineteenth century it was realized that the free sugars (not only the glycosides) existed as cyclic hemiacetals or hemiketals. Mutarotation, discovered in 1846 by Dubrunfaut, was now interpreted as being due to a change... 

Cyclic hemiacetals or hemiketals of sugars with a five-membered (tetrahydrofuran) ring are called furanoses, those with a six-membered (tetrahydropyran) ring pyran-oses. For sugars with other ring sizes see 2-Carb-5. 

This is a modified form of the 1980 recommendations [4]. Priority is now given to naming cyclic forms, since in most cases branched-chain monosaccharides will form cyclic hemiacetals or hemiketals. 

If the branched monosaccharide forms a cyclic hemiacetal or hemiketal, the chain which includes the ring atoms rather than any alternative open chain must be the basis of the name. Otherwise the parent is chosen according to the principles given in 2-Carb-2.1. 

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