With orthoesters

With orthoesters. Trimethyl orthoformate (TMOF) was found to be a very efficient chain transfer agent (25). Even one percent very markedly reduced the molecular weight of the PTHF (Fig. 6). In fact, it has been shown that the molecular weight of PTHF can be completely 

Some insight into the unusually high efficiency of TMOF was obtained by allowing the polymerization of THF in the presence of a large amount of TMOF (40%) to proceed for 14 days. Under these conditions degrada-tive chain transfer proceeded to the ultimate limit and only oligomers were isolated (Table 8). In this way it was clearly demonstrated that the end groups were both methoxy and that methyl formate was formed as a byproduct. 

Dreyfuss and Dreyfuss (25) explain these observations in terms of a transfer process which proceeds as follows  

Although the above reactions are most easily visualized as presented. 

When the chain transfer process is then completed in the following way (illustrated for clarity with a single resonance form), 

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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. 

Alkyl and aryl thiohydrazide derivatives react with orthoesters and trihalomethyls to afford 1,3,4-thiadiazoles. The reactions proceed via a thiosemicarbazone intermediate which cyclizes to eliminate either alcohol or hydrogen chloride. Treatment of the iV-thiohydrazide pyrazole 143 with triethyl orthoformate in acetic acid at reflux gave the 5-acetamido-l,3,4-thiadiazol-2-ylpyrazole 144 (Equation 51), and in the absence of acetic acid the 5-amino-l,3,4-thiadiazol-2-ylpyrazole 145 in 76% yield <2000JCM544>. 

Pyrrolo[l,2-rf [l,2,4]triazinones 21 were synthesized from methyl ester of /ra j-4-hydroxy-L-proline 72. The synthetic route involved formation of hydrazones followed by cyclisation with orthoesters <1998BMC349>. Similar reactions have been developed with 3-benzylindole-2-carbohydrazides 73 in reaction with triethyl orthoformate, giving the corresponding ring systems indolo[l,2-r][ 1,2,4]triazin-4-oncs 74 <2004JHC7>. 

Selective protection of 1,2- or 1,3-diols.1 Diols react with orthoesters in the presence of an acid catalyst (such as 10-camphorsulfonic acid, CSA) to form an orthoester that can be reduced, without isolation, by DIBAH to a monoacetal... 

Scheme 5.6 The competing glycosylation issue with orthoesters.

Scheme 5.7 The two-stage modification for glycosylation with orthoesters.

Scheme 5.15 Alternative strategies for efficient glycosylation with orthoesters.

The 2,3-disubstituted derivatives 316 are easily obtained by the cyclization of carboxamides 314 with orthoesters. 

A convienient route to pyrazolo[l,5-t/]-l,2,4-triazines utilizing pyrazol-5-carbohydrazide (128) has been reported (55JA1148). Thus, 128 R = H, afforded pyrazolo[l,5-cTl-l,2,4-triazine (131) on treatment with orthoesters, probably via acyclic intermediate 130. Treatment of 128 with orthoesters afforded mesoionic 129 (Scheme 17) (80JHC1291). Treatment of 4-ribosylpyrazol-5-aldehyde ethoxycarbonylhydrazone with cesium carbonate afforded C-ribosylpyrazolo[l,5-cf -l,2,4-triazin-4-one (83MI1). 

Table 20 Pyrido[2,3-e]-1,2,4-thiadiazine 1,1 -oxides 267 from the reaotion of 2-aminopyridine-3-sulfonamides 266 with orthoesters...

The synthesis of 2-alkoxymethylpteridines (antiallergic compounds) has also been achieved by the Taylor synthesis <1996EJM273> (Scheme 31). The 3-aminopyrazine-2-carboxamide 163 reacted with orthoesters to give 2-alkoxymethylpteridine derivative 164. Alternatively, 164 was synthesized by condensing 3-aminopyrazine-2-car-bonitrile 165 with the acetoxyamidine 166 followed by the base hydrolysis (Table 9). 

With orthoesters, tetramic acid 2b gives methylidene compounds (75) on heating in toluene. With excess triethyl orthoformate as solvent, 2b forms 75a in 90% yield. Intermediates (74) are not isolable, but react further with an excess of 2b. Similarly, a high tendency to form 75a is also reported for the reaction of 2b with ethoxymethylidene compounds 76a,b (67M564). In both cases 75a was furnished in 20% yield. Moreover, 77b (15%) and 78a (20%) were obtained (91TH1). According to X-ray... 

Cyclization of AT-aminoazoles with orthoesters, acids, acid chlorides, etc., constitutes another general route to fused s-triazoles or 1,3,4-... 

Alkoxy derivatives may be prepared from enaminoketones by reaction with orthoesters (Scheme 57) (70CB2760). 

The metal-promoted reactions of 1,2-dihydrazones with formaldehyde (see Scheme 35) can be compared with the purely organic reactions of 1,2-dihydrazones with orthoesters, which lead directly to macrocyclic compounds from which complexes of structural type (85) can be prepared.189190... 

The 1,3,6-benzotriazocine ring system was first synthesized by Hornyak, Lempert, and co-workers, who found that N-tosyl-o nitroanilines could be haloalkylated and then aminated to yield compounds 234 (R = H, Me R = H, Me, OMe). Hydrogenation of 234, followed by reaction with orthoesters, R2C(OAlk)3, produced compounds 235 (R = R2 = H, Me R1 = H, Me, OMe). If cyanogen bromide was used instead of orthoesters, triazocines 235 (R2 = NH2) resulted. Reduction of 234 (R = R = Me), followed by condensation with diethyl carbonate, gave urea 234 (R = R = Me, X = O). A similar reaction starting with 234... 

The condensation of the 1-methyl group in 2-benzopyrylium salts 92 with carbonyl derivatives such as aromatic aldehydes (70KGS1308) in acetic acid gives rise to 1-styryl-substituted salts 94. The reaction proceeds similarly with orthoesters (74KGS37), isocoumarin derivatives, and di-methylformamide (DMF) (80KGS193) or azomethines (82KGS465). The... 

The first results reported (41) showed that the mild acid hydrolysis of the five cyclic orthoesters 72-76 (Ri H ) gave the corresponding hydroxy-ester as the sole product of the reaction. It was found later by Capon and Grieve (58) that the hydrolysis of orthoester Ti (R=CH3 or C2H5) gave a mixture of hydroxy-ester (=70%) and lactone (30%). The hydrolysis of orthoesters 72-76 was subsequently repeated (59). It was confirmed that orthoester 73 indeed gave a =7 3 mixture of hydroxy-ester and lactone. A similar result was observed with orthoester 72 but the other three orthoesters 74-76 gave exclusively hydroxy-ester as previously reported. 

Reaction of isomeric 5-amino-3-morpholino-17/-l,2,4-triazolylcarbothiohydrazides 71 with orthoesters yielded the expected [l,2,4]triazolo[l,5-,7][l,2,4,6]tetrazepine-5(777)-thione 72 in the case of triethyl orthoacetate, but in other cases rearranged products such as 73-75 were obtained (Scheme 13). Possible explanations were given for the formation of the rearranged products <1997JHC1575, 2000JHC261>. 

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