Methanolic sodium methoxide

The primary synthesis of alkoxypyrimidines is exemplified in the condensation of dimethyl malonate with O-methylurea in methanolic sodium methoxide at room temperature to give the 2-methoxypyrimidine (854) (64M207) in the condensation of diethyl phenoxymalonate with formamidine in ethanolic sodium methoxide to give the 5-phenoxypyrimidine (855) (64ZOB1321) and in the condensation of butyl 2,4-dimethoxyacetoacetate with thiourea to give 5-methoxy-6-methoxymethyl-2-thiouracil (856) (58JA1664). 

Methyl-3,4-dinitropyrrole (170) undergoes some interesting reactions with nucleophilic reagents. With methanolic sodium methoxide it yields a product (171) which on treatment with trifluoroacetic acid gives the 2-methoxypyrrole (172) 78CC564). 

Isatin (190) is a compound with interesting chemistry. It can be iV-acetylated with acetic anhydride, iV-methylated via its sodium or potassium salt and O-methylated via its silver salt. Oxidation of isatins with hydrogen peroxide in methanolic sodium methoxide yields methyl anthranilates (81AG(E)882>. In moist air, O-methylisatin (191) forms methylisatoid (192). Isatin forms normal carbonyl derivatives (193) with ketonic reagents such as hydroxylamine and phenylhydrazine and the reactive 3-carbonyl group also undergoes aldol condensation with active methylene compounds. Isatin forms a complex derivative, isamic acid (194), with ammonia (76JCS(P1)2004). 

The following table gives exchange rates in methanolic sodium methoxide for a number of hydrocarbons and equilibrium acidities for some. Determine whether there is a correlation between kinetic and thermodynamic acidity in this series of compounds. If so, predict the thermodynamic acidity of the hydrocarbons for which no values are listed. 

The corresponding reaction with 2-methylamino-5-nitroaniline affords an unambiguous synthesis of l-methyl-6-nitroquinoxaIin-2-one, the A -mcthyl derivative of (6) this product is also obtained by treatment of (6) with methyl iodide and methanolic sodium methoxided ... 

Preparation of 9, 11 -Epoxy-17a-21 -Dihydroxy-16 -Methyl-4-Pregnene-3 0-Dione 21-Acetate To a stirred solution of 100 mg of the 9a-bromo-11(3,17a,2Ttrihydroxy-16 3-methyl-4-pregnene-3,20-dione 21-acetate in 3 ml of tetrahydrofuran and 1 ml of methanol under nitrogen was added 1.02 ml of 0.215 N methanolic sodium methoxide. After 10 minutes at 25°C, 0.2 ml of acetic acid was added and the methanol removed in vacuo. The residue was acetylated with 1.00 ml of pyridine and 0.5 ml of acetic anhydride at 60°C for 70 minutes. The mixture was taken to dryness in vacuo, water added, and the product extracted into chloroform. The residue was crystallized from ether-acetone to give pure 9(3,11 (3-epoxy-17a,21-dihydroxy-16(3-methyl-4-pregnene-3,20-dione 21-acetate. 

The 3-o-ch orophenvl-5-methvlisoxa2ole4-carboxylic acid, from which the acid chloride was prepared, was obtained by hydrolysis of the ester product of the reaction between o-chloro-benzohydroxamic chlorideand ethyl acetoacetate in methanolic sodium methoxide. Reaction with thionyl chloride gave the starting material. 

Step C Preparation of 3-Morpholino-4-(3-tert-Butylamino-2-Oxopropoxy)-1,2,5-Thia-diazole — The 1-toluenesulfonyloxy-2-oxo-3-tert-butylaminopropane, prepared as described in Step B, (11 mols) is added to 0.80 N methanolic sodium methoxide (15 ml) at 0°C. The mixture is stirred for 15 minutes at 0° to 5°C, treated with 3-morpholino-4-hydroxy-1,2,5-thiadiazole (4.29 grams) and then refluxed for 16 hours. The solvent is evaporated in vacuo and the residue is treated with excess potassium carbonate to provide 3-morpholino-4-(3-butylamino-2-oxopropoxy)-1,2,5-thiadiazole. 

Methyl 2-deoxy-P-v- yxo-hexopyranoside. A suspension of 170 mg. of the nitrobenzoylated hexoside (obtained in the preceding preparation) in 50 ml. of 0.01M methanolic sodium methoxide is stirred for 4 hours at room temperature. The solvent is removed at 40°C. under diminished pressure, and the residue is suspended in 15 ml. of water. The suspension... 

Deethoxycarbonylation of the acetyl derivative 31 is accomplished with methanolic sodium methoxide, and the resulting (i/4-3-acetyl-l//-azepine)tricarbonyliron(0) can be methylated at nitrogen with iodomethane and sodium hydride.226... 

The reactions of methanolic sodium methoxide with 2,4,6-triarylthiopyr-ylium perchlorates 61 have been subjected to many experimental investigations resulting in the chemical picture shown in Scheme 4. 

B. 2,5-Heptanedione. Methanolic sodium methoxide [Methanol, sodium salt] is prepared by cautiously adding small pieces of freshly cut sodium (5.67 g., 0.247 mole) to 200 ml. of cold methanol (Note 3) in a 500-ml., three-nccked flask equipped with a mechanical stirrer, a... 

A portion of the product was heated to reflux with methanolic sodium methoxide to convert it into the thermodynamic mixture of trans- (ca. 65%) and cis- (ca. 35%) isomers. Small amounts of the isomers were collected by preparative gas chromatography using an 8 mm. by 1.7 m. column containing 15% Carbowax 20M on Chromosorb W, and each isomer exhibited the expected spectral and analytical properties. The same thermodynamic mixture of isomers was prepared independently by lithium-ammonia reduction5 of 2-allyl-3-methyl-cyclohex-2-enone [2-Cyclohexen-l-one, 3-methyl-2-(2-propcnyl)-],6 followed by equilibration with methanolic sodium methoxide. 

Tetranitro derivative 90 (z-TACOT Section 12.10.15.5) treated with methanolic sodium methoxide at ambient temperature does not lead to simple product of nucleophilic substitution of a nitro group but provides compound 92. Its formation can be rationalized by introduction of the methoxy group into the 1-position, followed by scission of the remote triazole ring of 91 to give the final product. Compound 90 subjected to the vicarious nucleophilic substitution (VNS) conditions using either hydroxylamine or trimethylhydrazinium iodide gives a very insoluble red solid, which was identified as l,3,7,9-tetraamino-2,4,8,10-tetranitrobenzotriazolo[2,l- ]benzotriazole 93 (Scheme 5) <1998JOC3352>. 

With lower hydrochloric acid concentration and reversal of the mode of addition, i.e., acid to indanone-nitrite mixture, the intermediate 2-methyl-2-nitroso-l-indanone may also be isolated as its dimer. This can be isomerized to the isocarbostyril rapidly in refluxing methanolic sodium methoxide and more slowly in concentrated hydrochloric acid.4... 

Warm slides on a hot plate at 40 50°C remove epoxy resin by inserting slide into methanolic sodium methoxide for 3 min (2 g sodium metal to 110 mL methanol then add 100 mL benzene after dissolution use immediately). 

Treatment of chloroindolenine 7Vb-oxide (552), derived from yohimbine (74), with ethanolic potassium hydroxide gave 3-hydroxyyohimbine Nb-oxide (553). The same type of reaction occured, when 552 was treated either with methanolic sodium methoxide or with methanolic potassium cyanide, the products being 3-methoxyyohimbine iVb-oxide (554) and 3-cyanoyohimbine Nb-oxide (555), respectively (275). 

A total synthesis of (35, 4/ )-(+)-eldanolide (246), a sex attractant pheromone, has been reported (243). Compound 246 was synthesized by two different routes, both involving the butenolide 245 as the key precursor. The higher-yielding sequence is described here. Treatment of the tosylate acetal 242 with methanolic sodium methoxide led, as previously described by Hoffman and Ladner (244), to the epoxide 243. Addition of lithium diiso-butenylcuprate to 243 afforded 244, which after successive hydrolysis of the isopropylidene group, treatment with triethyl orthoformate, and pyrolysis,... 

O-Methylisouronium sulfate and S-alkylisothioureas were reacted with EMME in methanolic sodium methoxide or aqueous ethanol, respectively, to yield 2-methoxy- and 2-alkylthiopyrimidine-5-carboxylates (220) (07MI2 42JA794 59MI4 62JOC3614 87MI9). 

The fluorination of nitroalkanes has been described. A solution of acetyl hypofluo-rite, AcOF, is prepared by passing fluorine, diluted with nitrogen, into a cold suspension of hydrated sodium acetate in acetonitrile containing acetic acid. Adding a mixture of a nitroalkane and methanolic sodium methoxide yields the fluorinated nitroalkane, e.g. 1-fluoro-l-nitrocyclopentane from nitrocyclopentane417. A general method for alkylating nitroalkanes is exemplified by the reaction of the sodium nitronate 376 with the benzotriazole derivative 377 to yield 378418. 

Treatment of the nitronate salt 397 (from nitroethane and methanolic sodium methoxide) with benzene in the presence of trifluoromethanesulphonic acid gives acetophenone oxime, which is obtained mainly as the (E)-isomer 398433. 

Methanol, Hydrogen, Raney nickel catalyst, 0484 Methoxyacetyl chloride, 1165 4-Methoxy-3-nitrobenzoyl chloride, 2916 Methyl formate, Methanol, Sodium methoxide, 0834 3-Methyl-2-penten-4-yn-l-ol, 2384 Nitric acid, 4436... 

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