Synthesis of cyclic acetals

We noted earher that the reaction of an aldehyde with an alcohol to give an acetal is not favorable entropically. However, the simple expedient of using a diol to make the acetal ehminates this unfavorable entropy change. The most common alcohol used is for making cychc acetals 1,2-ethanediol (ethylene glycol). In this reaction, two molecules of reactant yield two molecules of product, and the entropy change is approximately zero. The acid catalyst is tolunesulfonic acid (TsOH), and benzene is the solvent. 

Ketones also react with ethylene glycol to give good yields of ketals. Distillation with toluene or benzene drives the position of the equilibrium toward products. Benzene and toluene co distill with water as a mixture with a constant boiling called an azeotrope. 

---

Cyclic Acetals. One of the most significant developments in the chemistry of sucrose was the synthesis of cyclic acetals which, despite many attempts, were not synthesized until 1974. The first synthesis of 4,6-O-benzylidenesucrose was achieved from the reaction of sucrose with Ot, Ot-dibromotoluene in pyridine (29). Since then, many new acetalating reagents have been used to give a variety of sucrose acetals, generally by transacetalation reactions. 

II. Summary of Developments Concerning the Synthesis of Cyclic Acetals. 73... 

It seems useful to begin with a summary of recent advances concerning the synthesis of cyclic acetals as a supplement to de Beider s discussion3 of the literature up to 1975. 

K. Furuta, T. Nagata, and H. Yamamoto, A direct synthesis of cyclic acetals from f - or y-hydroxy ethers by means of C-H activation, Tetrahedron Lett., 29 (1988) 2215-2218. 

Synthesis of Cyclic Acetals and Ketals Cyclization Mediated by Electrophiles... 

Scheme 15. Synthesis of Cyclic Acetals by Hydroxyselenenylation of Dialkenyl Ketones...

Martinet, P., Mousset, G., Colineau, M. Activated montmorillonite as a catalyst in the synthesis of cyclic acetals. Evidence of side reactions. C. R. Seances Acad. Sci. C. 1969, 268, 1303-1306. 

This ease of synthesis of cyclic acetals makes them appropriate for the preparation of certain well-defined, mono-substituted esters of different origin. 2,3 4,5-Di-0-isopropylidene-/8-D-fructopyranose has been used for the synthesis of certain phosphoramidate compounds. The acetal is dissolved in 20 ml of toluene and refluxed for 6 to 8 hours in the presence of phosphoramidic chloride. The sirupy l-[iV,W-bis-(2-chloroethyl)phos-phoramidic chloride] (5) is then used for the preparation of other derivatives, such as the phosphoramidate itself. Hydrolysis with ethanolic hydrogen chloride removes the isopropylidene groups and results in the formation of ethyl /3-D-fructopyranoside l-[iV,JV-bis-(2-chloroethyl)phosphoramidate]. 

Transacetalization is particularly suitable for the synthesis of cyclic acetals.931 932 It is sometimes an advantage first to prepare the starting acetal and then to perform the transacetalization operation in that reaction mixture.926 927 933 934... 

Synthesis of cyclic acetals Cyclic ketals (potential cosmetics ingredients) have been obtained in excellent yields from a cineole ketone under the action of microwave in solvent-free conditions or in toluene. The results reported compared very favorably with those obtained by use of conventional heating (Eq. (39), Table 4.11) [123]. 

Intramolecular amination with allylic acetates is used for the synthesis of cyclic alkaloids 175]. Cyclization of 293 affords the six-membered ring compound 294 rather than a four-membered ring. The reaction is particularly... 

The most general method for synthesis of cyclic enamines is the oxidation of tertiary amines with mercuric acetate, which has been investigated primarily by Leonard 111-116) and applied in numerous examples of structural investigation and in syntheses of alkaloids 102,117-121). The requirement of a tram-coplanar arrangement of an a proton and mercury complexed on nitrogen, in the optimum transition state, confers valuable selectivity to the reaction. It may thus be used as a kinetic probe for stereochemistry as well as for the formation of specific enamine isomers. 

In 1981, it was demonstrated (70) that anions of nitro compounds can be involved in C,C-coupling with allyl acetates at the allylic carbon atom with the use of metal complex catalysis. For many years, this observation did not come to the attention of chemists interested in the synthesis of cyclic nitronates. However, Trost demonstrated (71) that this process can be used in the synthesis of five-membered cyclic nitronates from olefins (18) containing two acyl groups in the different allylic positions (Scheme 3.21). 

A recently developed general procedure for the synthesis of cyclic nitroso acetals is based on the reaction of cyclic nitronates with C-nucleophiles under conditions of electrophilic catalysis (Scheme 3.153 for more details, see Section 3.5.2.3). 

A direct synthesis of cyclic quinone imine acetals has been accomplished by the treatment of substituted phenol ethers bearing an alkyl azido side chain with IBTA (Eq. 39) [96JCS(CC)1491]. The cyclization reaction proceeds smoothly in polar and low nucleophilic solvents such as CF3CH2OH and (CF3)2CH0H in the presence of 10% MeOH. 

We developed a method for the synthesis of a variety of cyclic acetals that utilizes bismuth triflate as a catalyst and does not require the use of a Dean-Stark trap for removal of water [102]. In this method, an aldehyde or ketone is treated with 1,2-bis (trimethylsiloxy)ethane in the presence of bismuth triflate. A comparison study using o-chlorobenzaldehyde showed that with ethylene glycol a low conversion to the dioxolane was observed after 2 h whereas the use of the 1,2-bis(trimethylsiloxy) ethane afforded the corresponding dioxolane in good yields. (Scheme 9). 

The carbamate derivatives of amino alcohols also proved applicable for the synthesis of cyclic hemiaminal derivatives. Through the ring closures of W-BOC-substituted 1,3-amino alcohols with aldehydes or acetals, 3-BOC-1,3-oxazine derivatives were obtained <1998TL6561, 1999J(P1)1933, 2006JOC8481, 2006T8687, 2006TL7923>. 

When five- or six-membered ring ethers can readily be formed by intramolecular alkoxymercuration of the initially formed alkenol, cyclic ethers are often the observed product (equation 219).341 This process has recently proven useful in the synthesis of spirocyclic acetals (equation 220).342... 

Although the Hay coupling has also been successfully used in the synthesis of cyclic oligoacetylenes (shown in the Section 1.3.3, Scheme 8) [6], for extended, macro-cyclic oligoacetylenes the modification presented by Eglinton and Galbraith [7a] is quite often the method of choice [2]. Here copper(II) acetate must be used in large excess, most commonly dissolved in pyridine or mixtures of pyridine and methanol... 

A generally applicable oxetane synthesis (e.g., 100 101) can be achieved by the anionic ring contraction of cyclic acetals fused to butanolide using organolithium reagents (Scheme 53) <2004SL651, CHEC-III(2.05.10.2)352>. 

---