Orthoform

They are colourless liquids with characteristic odours, and are prepared by the condensation of ketones with alkyl orthoformates in the presence of alcohols, or by the reaction of acetylenes with alcohols in presence of HgO and BF3. In some cases trichloroethanoic acid is used as the catalyst. They lose alcohol when heated and form vinyl ethers. Exchange of alcohol groups occurs when the ketals of the lower alcohols are boiled with alcohols of greater molecular weight. See acetals. 

The prefix is also used in orthophosphates, orthocarbonates, orthoformates and ortho-silicates, which are derivatives of POCOH), the hypothetical C(OH)4, HC(OH)3 and Si(OH)4 respectively in these the word ortho is always written in full. 

RCHO + RCHO —> RCOOCHjR 3. From ethyl orthoformate and the Grignard reagent, for example CsH aMgBr + CH(0C3H3)3 —... 

The ethyl orthoformate required in this preparation may be prepared by the action of sodium upon a mixture of chloroform and dry alcohol ... 

To a mixture of 250 ml of ether and 3 moles of freshly distilled acrolein ivere added about 3 moles of bromine at a rate such that the temperature could easily be maintained between -30 and -90°C (bath of dry-ice-acetone or liquid Nj). After persisting of the browncolour, the temperature was allowed to rise to 0°C. Freshly distilled ethyl orthoformate (3.25 moles) and 96% ethanol (30 ml) were added. 

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]. 

Oxidative carbonylation of alcohols with PdCh affords the carbonate 572 and oxalate 573(512-514]. The selectivity of the mono- and dicarbonylation depends on the CO pressure and reaction conditions. In order to make the reaction catalytic, Cu(II) and Fe(III) salts are used. Under these conditions, water is formed and orthoformate is added in order to trap the water. Di-/-butyl peroxide is also used for catalytic oxidative carbonylation to give carbonates and oxalates in the presence of 2,6-dimetliylpyridine(515]. 

Organophosphorus compounds. Phosphorus-carbon bond fonnation takes place by the reaction of various phosphorus compounds containing a P—H bond with halides or tritlates. Alkylaryl- or alkenylalkylphosphinates are prepared from alkylphosphinate[638]. The optically active isopropyl alkenyl-methylphosphinate 778 is prepared from isopropyl methylphosphinate with retention[639]. The monoaryl and symmetrical and asymmetric diarylphosphi-nates 780, 781, and 782 are prepared by the reaction of the unstable methyl phosphinate 779 with different amounts of aryl iodides. Tnmethyl orthoformate is added to stabilize the methyl phosphinate[640]. 

Carbocyanines with three methine groups can be prepared using Pvo equivalents of selenazolium quaternary salt and one equivalent of ethyl orthoformate in pyridine solution (53). 

With Lewis acids as catalysts, compounds containing more than one alkoxy group on a carbon atom add across vinyl ether double bonds. Acetals give 3-alkoxyacetals since the products are also acetals, they can react further with excess vinyl ether to give oligomers (228—230). Orthoformic esters give diacetals of malonaldehyde (231). With Lewis acids and mercuric salts as catalysts, vinyl ethers add in similar fashion to give acetals of 3-butenal (232,233). 

Additionally, Grignard reagent reacts with an alkyl orthoformate to form an acetal which is then hydrolyzed to the corresponding aldehyde usiag dilute acid. 

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... 

Aromatic compounds are formylated also by dichioromethyl methyl ether or trialkyl orthoformates (128). 

Otherwise, the main reactions at the methylene group are the dialkylation with alkyl haUdes (77), the acetylation with acetyl chloride which yields acetylma1 ononitrile [1187-11-7] (78), the Knoevenagel condensation, as well as the condensation with triethyl orthoformate, gives... 

This method, however, is not industrially practical because a large amount of dehydrating agent, such as ethyl orthoformate, is required to remove water formed in the reaction. Because water is an inhibitor of the reaction, the reaction system has to be kept under substantially anhydrous conditions. 

Reaction conditions depend on the reactants and usually involve acid or base catalysis. Examples of X include sulfate, acid sulfate, alkane- or arenesulfonate, chloride, bromide, hydroxyl, alkoxide, perchlorate, etc. RX can also be an alkyl orthoformate or alkyl carboxylate. The reaction of cycHc alkylating agents, eg, epoxides and a2iridines, with sodium or potassium salts of alkyl hydroperoxides also promotes formation of dialkyl peroxides (44,66). Olefinic alkylating agents include acycHc and cycHc olefinic hydrocarbons, vinyl and isopropenyl ethers, enamines, A[-vinylamides, vinyl sulfonates, divinyl sulfone, and a, P-unsaturated compounds, eg, methyl acrylate, mesityl oxide, acrylamide, and acrylonitrile (44,66). 

The yield of this reaction for R=R =C2H is 73% (15). Reagents are less toxic than the corresponding sulfates and less volatile than the orthoformates. Esters of phosphoms oxo-acids having beta hydrogens undergo olefin elimination upon pyrolysis, usually beginning at 160—200°C. 

Chain Transfer. A number of materials act as tme transfer agents in THF polymerization notable examples are dialkyl ethers and orthoformates. In low concentrations, water behaves as a transfer agent, and hydroxyl end groups are produced. The oxygen of dialkyl ethers are rather poor nucleophiles compared to THF and are therefore not very effective as transfer agents. On the other hand, orthoformates are effective transfer agents and can be used to produce alkoxy-ended PTHFs of any desired molecular weight (169). 

Condensation. Depending on the reaction conditions, a variety of condensation products are obtained from the reaction of aromatic amines with aldehydes, ketones, acetals, and orthoformates. 

Fig. 2. Synthesis of uma2enil (18). The isonitrosoacetanihde is synthesized from 4-f1iioroani1ine. Cyclization using sulfuric acid is followed by oxidization using peracetic acid to the isatoic anhydride. Reaction of sarcosine in DMF and acetic acid leads to the benzodiazepine-2,5-dione. Deprotonation, phosphorylation, and subsequent reaction with diethyl malonate leads to the diester. After selective hydrolysis and decarboxylation the resulting monoester is nitrosated and catalyticaHy hydrogenated to the aminoester. Introduction of the final carbon atom is accompHshed by reaction of triethyl orthoformate to...

Orthoesters are trivially named as derivatives of ortho acids such as triethyl orthoformate [122-51 -0] HC(OC2H )2, or named systematically as ethers, 1,1,1-triethoxymethane. 

Barbiturates (Veronal. Barbital, Luminal, Amytal), ethyl orthoformate, and other chemicals are produced commercially from sodium ethoxide. 

---