Triethyl reactions with

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...

Benzyl chloride readily forms a Grignard compound by reaction with magnesium in ether with the concomitant formation of substantial coupling product, 1,2-diphenylethane [103-29-7]. Benzyl chloride is oxidized first to benzaldehyde [100-52-7] and then to benzoic acid. Nitric acid oxidizes directly to benzoic acid [65-85-0]. Reaction with ethylene oxide produces the benzyl chlorohydrin ether, CgH CH20CH2CH2Cl (18). Benzylphosphonic acid [10542-07-1] is formed from the reaction of benzyl chloride and triethyl phosphite followed by hydrolysis (19). 

The neopentanedlol and triethyl orthoformate were purchased from Aldrich Chemical Co., Inc. and used as received. Failure to distil the methyl vinyl ketone, also obtained from Aldrich Chemical Co., to a clear, colorless liquid before use resulted in difficulty in determining the endpoint of the reaction with HBr. Therefore, the methyl vinyl ketone was distilled prior to use at reduced pressure. 

Androst-4-ene-3,17-dione (83) is converted into the enol ether (84) by reaction with triethyl orthoformate. Treatment of the enol ether (84) with DDQ in aqueous acetone gives the title dienone (85). This method is particularly suitable for A" -3-ketones substituted at the 6-position. 

The reaction with methanesulfonyl chloride in the presence of a proton abstracter like triethyl amine gave not the enamine, but a cyclic amino-sulfone (64). 

In order to expand the utility of the reaction, modification of the route to anilidomethylene malonic ester equivalents was developed. Simple condensation of triethyl orthoformate with cyanoacetic ester, acetoacetic ester, or malonic ester in the... 

The free acid analogue of the antipsoriatic agent etretinate (103) is prepared in substantially the same way as the parent compound. Thus, the aldehyde group in 98 is converted finally to the pho.sphonate (101) by sequential reduction (99), conversion to the chloride (100), and finally reaction with triethyl phosphite. Condensation of the ylide from 101 with the benzaldehyde 102 gives etretinate (103) saponification affords acitretin (104) [25]. 

Diphenylcyclopropenone, 47, 62 Dii henyldiacetylene, 45, 39 Diphenyl disulfide, oxidation to methyl benzenesulfinate, 46, 62 1,1-Diphenylethylene, reaction with N,or diphenylmtrone, 46,129 N,N -Diphi iiyli tiiyleni diamine, condensation with triethyl orthoformate, 47, 14... 

Triethyl phosphonoacetate, reaction of sodium derivative with cyclohexanone to yield ethyl cvclo hexy lideneacetate, 46, 45 1 nfluoroacetic anhydride, 46, 98 p,0 0 Trifluorostyrene, 47, 52 Trusopropvl phosphite as reagent in dechlorination of decachlorobi 2,4 cyclopentadienyl, 46, 93 1,3,5-Tnketones, from aroylationof 1,3-diketones, 46, 59 from 4-pyrones, 46, 59 Tnmethylamine oxide, reaction with x-octyl iodide to yield octanal, 47, 96... 

The ureas, e.g. 28 (R = NMe2), derived from the corresponding 2-(l-arylviny )benzylamines by reaction with (dimethylamino)carbamoyl chloride (Me2NCOCl) in the presence of triethyl-amine, undergo cyclization in refluxing phosphoryl chloride to the 5-aryl-3-(dimethylamino)-l//-2-benzazepin-3-amines. e.g. 29a.84 Prepared similarly are the 3-(4-methylpiperazin-l-yl) compound 29b and the 3-methyl derivative 29c from the corresponding urea and amide, respectively. 

The lithium 2-butenyl(triethyl)aluminate complex, prepared in situ from 2-butenyllithium and triethylaluminum, displayed poor diastereoselectivity in a reaction with benzaldehyde (anti/syn 56 44)7. (Z)-3-Alkoxy-substituted aluminate complexes such as A-C, however, give good diastereoselectivity in aldehyde addition reactions8. The reactions of A with aldehydes at —100 °C give the jyw-diol monoether with >95% diastereoselectivity and >80-95% regiose-... 

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. ... 

Several earlier methods (55,56) utilized a piperazinedione derivative in an Arbuzov-based sequence as a more stable source of the requisite iV-chloromethyl intermediate 51. Treatment of piperazine-1,4-dione with formaldehyde and phosphorus trichloride provided convenient access to this starting material. Subsequent reaction with either trimethyl or triethyl phosphite produced the iV-phosphonomethyl tetraester derivative 52, which has been hydrolyzed to GLYH3. 

Figure 17-22. Polyadduct from triethyl phosphate and phosphorous pentox-ide and reaction with hexanol to produce a diester.

Figure 9 A synthetic mixture of water-soluble carboxylic acids separated by anion-exchange chromatography. Column 0.3 cm x 300 cm Diaoion CA 08, 16-20 p (Mitsubishi Kasei Kogyo). Eluant 200 mM HC1. Detection reaction with Fe3-benzohy-droxamic acid-dicyclohexy carbodiimide-hydroxylamine perchlorate-triethyl amine with absorbance at 536 nm. Analytes (1) aspartate, (2) gluconate, (3) glucuronate, (4) pyroglutamate, (5) lactate, (6) acetate, (7) tartrate, (8) malate, (9) citrate, (10) succinate, (11) isocitrate, (12) w-butyrate, (13) a-ketoglutarate. (Reprinted with permission from Kasai, Y., Tanimura, T., and Tamura, Z., Anal. Chem., 49, 655, 1977. 1977 Analytical Chemistry).

In his approach toward selenium-containing heterocycles with potential biological activity, Abdel-Hafez reacted 2-amino-3-(4,5-dihydro-17/-imidazol-2-yl)-4,5,6,7-tetrahydro-l-benzoselenophene 297 with triethyl orthoformate and benzaldehyde to generate the tricyclic systems 296 and 298, respectively (Scheme 21) <2005RJ0396>. Similarly, reaction with carbon disulfide gave the corresponding thiourea 299. 

An attempt to convert the organocalcium iodide [Cs(l,2,4-(SiMe3)3)H2]CaI(THF) to a hydride complex by reaction with NaBEt3H lead instead to the triethyl borohydride complex 167.392 Spectroscopic data indicate that the... 

Treating 644 with triethyl orthoformate gave l,2-dihydro-l-oxo[l,2,4]-triazino[4,5-a]indole 648, whose reaction with phosphorus oxychloride or phosphorus pentasulfide gave 650 and 649, respectively. Both reacted with hydrazine to give 651, which then was converted into [l,2,4]triazolo[3, 4 -/][1,2,4]triazino[4,5-a]indoles 652 and 653 by reaction with formic or acetic acid, respectively (80JHC77). 

Electrophilic substitution of the ring hydrogen atom in 1,3,4-oxadiazoles is uncommon. In contrast, several reactions of electrophiles with C-linked substituents of 1,3,4-oxadiazole have been reported. 2,5-Diaryl-l,3,4-oxadiazoles are bromi-nated and nitrated on aryl substituents. Oxidation of 2,5-ditolyl-l,3,4-oxadiazole afforded the corresponding dialdehydes or dicarboxylic acids. 2-Methyl-5-phenyl-l,3,4-oxadiazole treated with butyllithium and then with isoamyl nitrite yielded the oxime of 5-phenyl-l,3,4-oxadiazol-2-carbaldehyde. 2-Chloromethyl-5-phenyl-l,3,4-oxadiazole under the action of sulfur and methyl iodide followed by amines affords the respective thioamides. 2-Chloromethyl-5-methyl-l,3,4-oxadia-zole and triethyl phosphite gave a product, which underwent a Wittig reation with aromatic aldehydes to form alkenes. Alkyl l,3,4-oxadiazole-2-carboxylates undergo typical reactions with ammonia, amines, and hydrazines to afford amides or hydrazides. It has been shown that 5-amino-l,3,4-oxadiazole-2-carboxylic acids and their esters decarboxylate. 

In the case of the synthesis of 10,19,19,19-2H4-vitamin A, the most useful for biological studies, three deuterium atoms were incorporated into /i-ionone 30, in >98% by deuterium exchange with excess D2O in the presence of Na02H (and pyridine). The tri-deuteriated 30, utilized in Wittig-Horner reaction with dideuterio triethyl phosphonate, provided tetradeuteriated ethyl /J-ionilidene acetate 31 with more than 98% 2H4 (by NMR). No deuterium loss in the subsequent synthetic steps was observed as evidenced by MS and NMR analysis. 

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