Trimethyl orthoformate

Two efficient syntheses of strained cyclophanes indicate the synthetic potential of allyl or benzyl sulfide intermediates, in which the combined nucleophilicity and redox activity of the sulfur atom can be used. The dibenzylic sulfides from xylylene dihalides and -dithiols can be methylated with dimethoxycarbenium tetrafiuoroborate (H. Meerwein, 1960 R.F. Borch, 1968, 1969 from trimethyl orthoformate and BFj, 3 4). The sulfonium salts are deprotonated and rearrange to methyl sulfides (Stevens rearrangement). Repeated methylation and Hofmann elimination yields double bonds (R.H. Mitchell, 1974). 

The intramolecular oxidative earbonylation has wide synthetie applieation. The 7-lactone 247 is prepared by intramolecular oxycarbonylation of the alke-nediol 244 with a stoichiometric amount of Pd(OAc)2 under atmospheric pres-sure[223]. The intermediate 245 is formed by oxypalladation, and subsequent CO insertion gives the acylpalladium 246. The oxycarbonylation of alkenols and alkanediols can be carried out with a catalytic amount of PdCl2 and a stoichiometric amount of CuCb, and has been applied to the synthesis of frenolicin(224] and frendicin B (249) from 248[225]. The carbonylation of the 4-penten-l,3-diol 250, catalyzed by PdCl2 and CuCl2, afforded in the c -3-hydroxytetrahydrofuran-2-aeetie acid lactone 251[226J. The cyclic acetal 253 is prepared from the dienone 252 in the presence of trimethyl orthoformate as an accepter of water formed by the oxidative reaction[227]. 

The water of hydration of these complexes can be replaced with other coordinating solvents. For example, the ethanol and methanol solvates were made by dissolving the hydrates in triethyl and trimethyl orthoformate, respectively (81,82). The acetic acid solvates are made by treating the hydrates with acetic anhydride (83). Conductivity and visible spectra, where appHcable, of the Co, Ni, Zn, and Cu fluoroborates in A/A/-dimethylacetamide (L) showed that all metal ions were present as the MLg cations (84). Solvated fluoroborate complexes of, Fe +, Co +, , Cu +, and in diethyl... 

Cinnamaldehyde dimethylacetal is prepared by the method used to prepare the corresponding diethylacetal. A mixture of 66.0 g. (0.5 mole) of Aldrich Chemical Company, Inc.), 100 g. (1.06 mole) of trimethyl orthoformate (Eastman Organic Chemicals), 450 ml. of anhydrous methanol (J. T. Baker Chemical Company), and 0.5 g. ofp-toluenesulfonic acid monohydrate (Fisher Scientific Company) is stirred at room temperature for 24 hours. At the end of this time the alcohol is removed with a rotary evaporator and the residue is distilled to give 81-83 g. (91-93%) of cinnamaldehyde dimethylacetal, b.p. 93—96° (0.2 mm.). 

Butanedione, TMOF (trimethyl orthoformate), CSA, MeOH, 60-82% yield. ... 

A, A, A, A -tetramethylethylenediamine trimethyl orthoformate tetrapropylammonium perruthenate tetraphenylporphyrin sulfonated triphenylphosphine triisopropylbenzensulfonyl chloride triphenylcarbenium tetrafluoroborate tetrabutylammonium triphenylmethanethiolate toluenesulfonyl... 

In contrast to the Vilsmeier formylation the formylation with trimethyl orthoformate in trifluoroacetic acid proceeds with high selectivity so that only the /3-monoformylated deuteroporphyrin derivatives 8 are formed without any methinc substituted or diformylated products.1073 6... 

A completely different concept13 makes use of a highly reduced bilane 5 which is oxidatively cyclized to an isobacteriochlorin 6 with copper(II) acetate. The ring closure is initiated by ester cleavage with trifluoroacetic acid and decarboxylative formylation with trimethyl orthoformate to yield a dialdehyde. One of the aldehyde functions forms the desired methine bridge whereas the other is lost during cyclization. 

Triethylamine, 61,83,87,88,94,99,100,112 Triethylamine N-oxide, 84 Triethylbenzylammonium chloride, 49 Triethylsilane, 104,127.128 Trifluoroacetic acid, 59 Trimethyi-m-dimethylaminophenylsilane, 40 Trimethyl orthoformate, 109... 

Notes, (a) Using trimethyl orthoformate, -ketoacetals are obtained. 

Sulfonic esters are most frequently prepared by treatment of the corresponding halides with alcohols in the presence of a base. The method is much used for the conversion of alcohols to tosylates, brosylates, and similar sulfonic esters. Both R and R may be alkyl or aryl. The base is often pyridine, which functions as a nucleophilic catalyst, as in the similar alcoholysis of carboxylic acyl halides (10-21). Primary alcohols react the most rapidly, and it is often possible to sulfonate selectively a primary OH group in a molecule that also contains secondary or tertiary OH groups. The reaction with sulfonamides has been much less frequently used and is limited to N,N-disubstituted sulfonamides that is, R" may not be hydrogen. However, within these limits it is a useful reaction. The nucleophile in this case is actually R 0 . However, R" may be hydrogen (as well as alkyl) if the nucleophile is a phenol, so that the product is RS020Ar. Acidic catalysts are used in this case. Sulfonic acids have been converted directly to sulfonates by treatment with triethyl or trimethyl orthoformate HC(OR)3, without catalyst or solvent and with a trialkyl phosphite P(OR)3. ... 

Alkyl aryl ketones can be converted to arylacetic acid derivatives in an entirely different manner. The reaction consists of treatment of the substrate with silver nitrate and I2 or Br2, ° or with thallium nitrate, MeOH, and trimethyl orthoformate adsorbed on Montmorillonite K-10 clay, an acidic clay. ... 

C,oH,403 707-07-3) see Betamethasone benzoate trimethyl orthobutyrate (C7H, j03 43083-72-/) see Difluprednate trimethyl orthoformate... 

AcetaUzation of benzaldehyde with trimethyl orthoformate can be carried out with a series of MOFs constructed from In and BDC or BTC ligands with open In sites. The catalysts are even stable in aqueous medium and can be reused without loss of activity. Owing to the small pores of these MOFs, the reaction only takes place at the outer surface of the crystals [54]. In another MOF constructed from In and 4,4 -(hexafluoroisopropylidene)bis(benzoic acid), the same reaction takes place inside the pores [55]. 

In a similar vein, condensation of the substituted anthranilamide 96 with trimethyl orthoformate affords directly the quinazolone 98. Reaction with phosphorus... 

Dining attempted preparation of trimethyl orthoformate, addition of sodium to an inadequately cooled chloroform-methanol mixture caused a violent explosion. See Ethanol (or methanol), Potassium sulfide, above See Sodium methoxide, below... 

In addition to aldehydes and a-diketones, a-ketoesters can also be used in the domino process, as shown by Tietze and coworkers [396]. Reaction of methyl pyruvate 2-791 with dimethylbarbituric acid (2-747) and the enol ether 2-792 in the presence of trimethyl orthoformate (TMOF) and a catalytic amount of EDDA gave the cycloadduct 2-793 in 84% yield (Scheme 2.176). 

The 3,4-dihydro-27/,6//,lltf//-[l,3]oxazino[2,3- ][l,3]benzoxazine 405 was Stained by treating 3-(2-hydroxyben-zamido)-l-propanol 404 with trimethyl orthoformate and formic acid (Equation 48) < 1999W099/33469>. 

A patent procedure for formation of compounds 19 from simple tartaric acid derivatives has appeared <06USP047129> and various new routes to chiral dioxolanones include synthesis of dioxolan-2-ones either by transition metal-mediated asymmetric synthesis <06T1864> or enzyme-mediated kinetic resolution <06H(68)1329> and a new synthesis of the chiral dioxolan-4-ones 21 from lactic or mandelic acid involving initial formation of intermediates 20 with trimethyl orthoformate in cyclohexane followed by reaction with pivalaldehyde <06S3915>. 

Methyl cc-D-glucofuranosidurono-6,3-lactone (26) may be obtained exclusively by reaction of 4 with trimethyl orthoformate in the presence of boron trifluoride etherate.28 Its 2,5-dimethyl ether (27) is formed by methyl iodide-silver oxide methylation29,30 (Purdie-Ir-... 

While halogenation and Sandmeyer reactions are suitable for preparation of oxazolyl halides, benzoxazolyl halides with halogen on the benzene ring moiety may be synthesized via other approaches. For instance, 5-halobenzoxazoles were prepared by treating 4-halo-2-aminophenols with trimethyl orthoformate and concentrated aqueous HC1 [6]. 

When the pyrrolo[l,2-c]oxazole 269 was treated with trimethyl orthoformate in the presence of BF3 Et20, in dichloromethane at — 78 °C, a mixture of compounds was obtained from which the expected 5-dimethoxymethyl derivative, 270, was isolated in poor yield (12%) with another dimethoxylated compound 271 (23%). The formation of 271 could be explained by the addition of the formyl cation equivalent at C-7, followed by the protonation at C-6 of the resulting enamide 272 leading to the electrophilic iV-acyliminium ion 273 (Scheme 40). The regioselectivity of this electrophilic addition of trimethylorthoformate to the silyloxypyrrole 269 at C-7, in a non-vinylogous manner, is unusual <1999TL2525>. 

The reaction of 2-hydroazinobenzothiazole 388 with trimethyl orthoformate or trimethyl orthobenzoate allows to prepare compounds 91 and 4 respectively, in poor yield (Scheme 47) <1996EJM575>. 

After treatment with an excess of trimethyl orthoformate, the hydrazino-isoborneol derivatives 412, via the corresponding dipoles, and reaction with phenylisocyanate, furnish stereoselectively oxazolo[3,2-A [l,2,4]triazoles 50 (Equation 85) <2002TL607, 2000PAC1721, 1995JOC1720>. 

The triazoloxazine 294 containing the saturated oxazine moiety was synthesized by Knight and Leeper <1998J(P1)1891> treatment of the hydrazinium salt 293 with trimethyl orthoformate yielded the product 294 in quantitative yield. 

Tris(phenylthio)methyllithium, (QHsS)3CLi (1). Tris(phenylthio)methane is prepared from thiophenol and trimethyl orthoformate. 

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