Cyclic orthoesters

Orthoester, Cyclic HgBr Ring opening (l->5)-a-L-arabo- furanan 50 — 59.5 -90 (119)... 

Orthoester, Cyclic HgBrj Ring opening (l- 5)-oe-L-arabo-furanan 20 — 23 -85 (120)... 

Orthoester, Cyclic Trimer 1,6-Anhydro Glucose HgBrj Ring opening (l- 3)- -D-gluco- pyranan 13-20 30 -9 (121)... 

Selective removal of the hydroxyl protecting groups included in this review is generally difficult to achieve and of little practical importance. Selective hydrolysis of cyclic orthoesters to give monoesters merits attention for its practical interest. 

Three possible mechanisms for the Serini reaction were originally suggested. These proceed via (a) a A -enol acetate, (b) a A -epoxide, or (c) a cyclic orthoester ... 

Imidazo[l,2-c/][l,2,4]triazines 488 were prepared (78USP4096257) from the reaction of 2-imidazocarboxylic acid hydrazide 487 with orthoesters. They inhibited cyclic-AMP phosphodiesterase in the mouse skin phosphodiesterase test and had antiasthina. 

The reaction between the cyclic orthoester 8 and diethyl chlorophosphite 9 leads via transesterification to the two acetals 4 and 5, which cannot be separated by distillation. 

Unsymmetrical ethers may be produced from the acid-promoted reactions of aldehydes and organosilicon hydrides when alcohols are introduced into the reaction medium (Eq. 173).327,328 An orthoester can be used in place of the alcohol in this transformation.327 335 A cyclic version of this conversion is reported.336 Treatment of a mixture of benzaldehyde and a 10 mol% excess of triethylsilane with methanol and sulfuric, trifluoroacetic, or trichloroacetic acid produces benzyl methyl ether in 85-87% yields.328 Changing the alcohol to ethanol, 1-propanol, 2-propanol, or 1-heptanol gives the corresponding unsymmetrical benzyl alkyl ethers in 45-87% yield with little or no side products.328 A notable exception is the tertiary alcohol 2-methyl-2-propanol, which requires 24 hours.328 1-Heptanal gives an 87% yield of //-lie ply I methyl ether with added methanol and a 49% yield of benzyl n-heptyl ether with added benzyl alcohol under similar conditions.328... 

Addition of diols to the carbonyl lactone group leads to the formation of cyclic orthoesters. Compounds containing a spiro, cyclic orthoester inter-linkage at the anomeric carbon atom are of interest, as this type of structure is found in the oligosaccharide antibiotics orthosomycins (91) (such as ever-ninomicin, flambamycin, and avilamycin). 

Further, a large number of examples with simple alkyl substituents [168, 171, 176-184], cyclic alkanes [185], aryl substituents [177, 186-192], olefmic substituents [78, 177, 193-196], deuterated compounds [172], thioether groups [171], ester groups [197], orthoesters [198, 199], acetals [168, 182, 200-204], silyl-protected alcohols [198, 205-211], aldehydes [212], different heterocycles [213-217], alkyl halides [218, 219] and aryl halides [192, 220-223] have been reported. A representative example is the reaction of 92, possessing a free hydroxyl group, an acetal and a propargylic ether, to 93 [224] (Scheme 1.40). 

Hydroformylation of unsaturated amines offer a convenient synthetic access to cyclic AT.O-hemiacetals. If performed in the presence of alcohols or orthoesters AT,O-acetals are formed. With additional N-nucleophiles N,N-acetals are obtained. These compounds are synthetically attractive building blocks and were therefore used as a key step in the synthesis of various natural products [27,35]. Thus the synthesis of (+)-prosopinine starting from enantiopure (T)-scrinc leads to a cyclic N,O-acetal functionality with the required functionality for the attachment of the side chain (Scheme 6) [36]. 

Aromatic and a-substituted aliphatic aldehydes react with oxiranes under neutral conditions to yield 1,3-dioxoIanes [35] whereas a-unsubstituted aldehydes undergo a simple aldol condensation under such conditions. In a somewhat similar manner, perfluorocarboxylic esters react with oxiranes to produce cyclic orthoesters (-50%) [36]. The corresponding reaction with non-fluorinated esters fails. 

Li S, Dory P. Hydrolysis of cyclic orthoesters experimental observations and theoretical rationalization. Tetrahedron 1996 52 14841. 

Similar experiments were also carried out with dichloroketene diethyl and dimethyl acetals but no intermediate could be detected. This is readily explained since the cyclic ketene acetals undergo acid-catalysed hydration about 30 times more rapidly than the corresponding acyclic ones (Straub, 1970 Chiang et al., 1974 Kresge and Straub, 1983) whereas cyclic hemi-orthoesters undergo acid-catalysed breakdown 50-60 times more slowly than the corresponding acyclic ones do (see p. 70). Therefore the ratio of rate constants favourable for the detection of the cyclic hemiorthoesters becomes unfavourable with the acyclic hemiorthoesters. 

Calculated equilibrium constants and free energies for the formation of cyclic hemi-orthoesters from the corresponding esters at 25° °... 

Orthoesters. The value of cyclic orthoesters as intermediates for selective acylation of carbohydrates has been demonstrated (73). Treatment of sucrose with trimethylorthoacetate and DMF in the presence of toluene-p-sulfonic acid followed by acid hydrolysis gave the 6-0-acetylsucrose as the major and the 4-0-acetylsucrose [63648-80-6] as the minor component. The latter compound underwent acetyl migration from C-4 to C-6 when treated with an organic base, such as / -butylamine, in DMF to give sucrose 6-acetate in >90% yield (74). When the kinetic reagent 2,2-dimethoxyethene was used,... 

Hydrogenolysis of cyclic orthoesters with diborane (a method using lithium aluminum hydride-aluminum chloride had been described for 1,2-orthoesters37) has been shown to be a route to cyclic acetals38 thus, a mixture of the endo and exo isomers of methyl 3,4-0-(ethoxy-ethylidene)-/3-L-arabinopyranoside led to methyl endo-3,4-0-ethy]i-dene-/3-L-arabinopyranoside (yield 66%). 

Summarizing, it may be concluded that the ease of hydrogenolysis is (1) cyclic orthoester > isopropylidene acetal, cyclohexylidene acetal > benzylidene acetal > ethylidene acetal > methylene acetal, and (2) 5,6-O-linked and 3,5-O-linked > 1,2-0-linked acetals. 

The reactivity of functional groups presenting some similarities to cyclic acetals, such as cyclic orthoesters, and stannylidene and amide acetals, falls outside the scope of the present article, but attention has to be drawn to the fact that they may be considered to be special types of acetals having distinct properties, and a growing interest is focused... 

S. S. Battacharjee and P. A. J. Gorin, Hydrogenolysis of cyclic and acyclic orthoesters of carbohydrates with lithium aluminium hydride-aluminium trichloride, Carbohydr. Res. 72 57 (1970). 

As a class of compounds, nitriles have broad commercial utility that includes their use as solvents, feedstocks, pharmaceuticals, catalysts, and pesticides. The versatile reactivity of organonitriles arises both from the reactivity of the C=N bond, and from the ability of the cyano substituent to activate adjacent bonds, especially C—H bonds. Nitriles can be used to prepare amines, amides, amidines, carboxylic acids and esters, aldehydes, ketones, large-ring cyclic ketones, imines, heterocycles, orthoesters, and other compounds. Some of the more common transformations involve hydrolysis or alcoholysis to produce amides, acids and esters, and hydrogenation to produce amines, which are intermediates for the production of polyurethanes and polyamides. An extensive review on hydrogenation of nitriles has been recendy published (10). 

Indeed, as shown by Verin and Kuznetsov (89UP1), the oxidation of 159 with hydrogen peroxide in ethanol gives rise to cyclic orthoester 217, and the formation of this compound corroborates the mechanism suggested earlier for this reaction. 

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