Monoacetalization

The optically active 1,4-cyclohexenediol monoacetate 525, prepared by hydrolysis of the me.so-diacetate with lipase, was converted into the optically pure cyclohexenone 526 by an elimination reaction in the presence of ammonium formate. Optically active carvone (527) was prepared from 526[343],... 

In addition to tetrabutylphosphonium chloride, typical phosphonium salts that can be produced include tetraoctylphosphonium bromide [23906-97-0], tetrabutylphosphonium acetate [17786-43-5] (monoacetic acid), and tetrabutylphosphonium bromide [3115-68-2]. Inmost cases, these compounds can be prepared with alternative counterions. 

The synthetic techniques of in generation of the quinone and utilisation of quinone monoacetals avoid the problems of instability, sequential... 

Quinone monoacetals such as 2-methoxyben2oquinonemonoacetal [64701-03-7] (66) show regiospeciftc addition of active methylene compounds (66), yielding 83% (67) and 63% (68) on reactions with ethyl malonate. 

Thallium trinitrate oxidi2es naphthols and hydroquinone monoethers, respectively, to quinones and 4,4-diaIkoxycyclohexa-2,5-dienones, eg, 4,4-dimethoxy-2-methyl-2,5-cyclohexadienone [57197-11 -2] (108) (111,112). The yield of (108) is 89%. Because the monoacetal is easily converted to the quinone, the yield of 5-hydroxy-l,4-naphthoquinone [481-39-0] is 64%. 

Reaction of carboxylate ion with nitrophenyl sulfites gives the carboxylate -nitrophenyl esters. If the -nitrophenyl sulfite is unsymmethcal (02NCgH40S(0)0R, where R is ethyl or phenyl), carboxylate attacks the -nitrophenyl side (69). Some amino acids react with methyl and benzyl sulfites in the presence of -toluenesulfonic acid to give methyl and benzyl esters of the amino acids as -toluenesulfonate salts (70). With alcohols, the conversion of henzil to a monoacetal upon addition of sulfuric acid to the henzil in methanol and dimethyl sulfite proceeds in high yield (71). 

Cellulose acetate [9004-35-7] is the most important organic ester because of its broad appHcation in fibers and plastics it is prepared in multi-ton quantities with degrees of substitution (DS) ranging from that of hydrolyzed, water-soluble monoacetates to those of fully substituted triacetate (Table 1). Soluble cellulose acetate was first prepared in 1865 by heating cotton and acetic anhydride at 180°C (1). Using sulfuric acid as a catalyst permitted preparation at lower temperatures (2), and later, partial hydrolysis of the triacetate gave an acetone-soluble cellulose acetate (3). The solubiUty of partially hydrolyzed (secondary) cellulose acetate in less expensive and less toxic solvents such as acetone aided substantially in its subsequent commercial development. 

Cyclic diesters are often even better substrates forlipases and esterases than acyclic derivatives. Small-ring monoacetates (28, n — 1-3) are obtained in higher yield and ee than the larger derivatives (for 28, n = 4 is only 50%) (43). Hydrolysis of tetrahydrofuran diester results in monoester (29) of ee > 99% (44). 

The synthetic utihty of the above transformations stems from the fact that many monoesters obtained as a result of hydrolysis may be converted to pharmaceutically important intermediates. For example, the optically active glycerol derivative (27) is a key intermediate in the production of P-blockers. Akyl derivative (25) may be converted into (5)-paraconic acid [4694-66-0] ((5)-5-oxo-3-tetrahydrofurancarboxyhc acid) that is a starting material for the synthesis of (3R)-A-factor. The unsaturated chiral cycHc monoacetate (31) is an optically active synthon for prostaglandins, and the monoester (29) is used for the synthesis of platelet activating factor (PAF) antagonists. 

The reaction is carried out over a supported metallic silver catalyst at 250—300°C and 1—2 MPa (10—20 bar). A few parts per million (ppm) of 1,2-dichloroethane are added to the ethylene to inhibit further oxidation to carbon dioxide and water. This results ia chlorine generation, which deactivates the surface of the catalyst. Chem Systems of the United States has developed a process that produces ethylene glycol monoacetate as an iatermediate, which on thermal decomposition yields ethylene oxide [75-21-8]. 

A monoacetate can be isolated by continuous extraction with organic solvents such as cyclohexane/CCl4. 

Trichloroacetaldehyde (chloral) reacts with glucose in the presence of sulfuric acid to form two monoacetals and four diacetals. The trichloro acetal is cleaved by reduction (H2, Raney Ni, 50% NaOH, EtOH, 15 min). The trichloro acetal can probably be cleaved with Zn/AcOH [cf. ROCH(R )OCH2CCl3 cleaved by Zn/ AcOH, AcONa, 20°, 3 h, 90% yield ]. 

Catalytic hydrpgenation in acetic anhydride-benzene,- moves the aromatic benzyl ether and forms a monoacetate hydrogenation in ethyl acetate re-moves the aliphatic benzyl ether to give, after acetylation, the diacetate. ... 

The chloromethyl derivatives may be prepared from pentaerythritol via the trichloride or trichloride monoacetate (Figure 19.13). 

Similar pentaerythritol cryptands have been prepared by a slight modification of the above approach. Although the general strategy is as illustrated in Eq. (8.11), atfetal formation is accomplished by reaction of pentaerythritol with paraformaldehyde. This reaction leads to diacetal 12 which is hydrolyzed in dilute H2SO4 to yield the monoacetal, 13. The latter is then used in a fashion similar to that described in Eq. 8.10, above. 

Rubin and Blossey standardized the experimental conditions for the Serini reaction, using freshly activated zinc in refluxing xylene for 20-24 hr with vigorous stirring yields of68-100 % could then be obtained. They noted, however, that the presence of a 16a- or -methyl group markedly decreased the yield, and that a primary-secondary glycol monoacetate failed to react. 

An apparently related reaction involves iodination in pure methanol in the presence of calcium chloride. The main product is the 21,21-d3-iodo derivative, which on reaction with acetate ion gives, surprisingly, the 21-monoacetate ... 

A monoacetate can be isolated by continuous extraction with organic solvents such as cyclohexane/CCI4. Monoacylation can also be achieved by ion exchange resin or acid-catalyzed transesterification. 

Scb m 7.1S. Selective cis or tions double conjugate addition of Et Zn to o/clohoradlenone monoacetal 66. 

A variant on this theme contains mixed acyl groups. In the absence of a specific reference it may be speculated that the synthesis starts with the diacetyl derivative (15). Controlled hydrolysis would probably give the monoacetate (16) since the ester para to the ketone should be activated by that carbonyl function. Acylation with anisoyl chloride followed by reduction would then afford nisobuterol (18). 

In order to prepare the monoacetate, the crude diacetate is suspended in 150 cc of methanol and, after adding 1.5 cc, concentrated hydrochloric acid, heated to boiling for 15 minutes in a nitrogen atmosphere. The crude monoacetate mhich separates upon the addition of meter after cooling is filtered off, meshed end dried in vacuo over calcium chloride at room temperature. The pure 17-ecetete, obtained after repeated recrystellizetions from methylene chloride/hexane has a MP of 161° to 162°C. 

A higher glycol yield (approximately 94%) than from the ethylene oxide process is anticipated. However, there are certain problems inherent in the Oxirane process such as corrosion caused hy acetic acid and the incomplete hydrolysis of the acetates. Also, the separation of the glycol from unhydrolyzed monoacetate is hard to accomplish. 

The first known pseudo-hexose, pseudo-a-DL-toZopyranose (34) was prepared by reduction of the keto-acid monoacetate (30) 26, 27). This intermediate, which had been used by Daniels, Doshi, and Smissman (9, JO) for a synthesis of shikimic acid, is prepared from the Diels-Alder adduct (31) of 2-acetoxyfuran and maleic anhydride, by a remarkable series of transformations. 

The monoacetate 9a (R1 = Ac) and the diacetate 10a (R1 = R2 = Ac) are obtained by treatment of 8 with acetic anhydride in anhydrous pyridine at room temperature 4 the oxo group in position 5 of 8 is more reactive towards acetylation. Similarly, the S,S-dioxidc of 8 can be converted to the bisacetylated S,5-dioxide of 10a in 78 % yield.74 Methylation of 8 with diazomethane gives 9c (65 % yield), along with 14 % of the 3-methoxy compound 11. Other alkylation agents, such as dimethyl sulfate in the presence of potassium carbonate, selectively give 9c, albeit in lower (30 %) yield.90 The dimethyl enol ether 10c (R1 = R2 = Me) is obtained by a subsequent methylation of 9c (R1 = Me) with dimethyl sulfate and potassium teri-butoxide.90... 

The fact that with acetal 1 (R1 = H R2 = CH3) a lower stereoselectivity is observed than with the acetals where R1 = Ft or C6II5 suggests that the bulkiness of the substituent at the acetal center also plays an important role in fixing the conformation of the transition state. With 1 bearing a hydrogen atom at the acetal center (R1 = II), the acetyl group is allowed to occupy the quasiequatorial position (3B) and the addition reaction therefore proceeds with no or only a weak chelation control. The same presumably holds for the elyoxal monoacetal 1 (Ri = R2 = M). 

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