Hydroxy methylenes

Cyclopropyl-a-hydroxy methylene)-3,5-dioxocyclohexanecarboxylic acid ethyl ester [95266-40-3]... 

P-Hydroxy-A-norpregn-3(5)-en-2-one (7) A solution of the hydroxy-methylene steroid (5) (24.8 g) dissolved in 240 ml of acetic acid and 240 ml of ethyl acetate is ozonized at — 10° with one molar equivalent of ozone. The resulting solution is diluted with 240 ml. of water and 60 ml of 30 % hydrogen peroxide and allowed to stand overnight. The solution is diluted with 1.5 liters of water and extracted with 3 x 700 ml portions of ethyl acetate. The combined extracts are washed with water, saturated sodium chloride solution, dried over sodium sulfate and concentrated to dryness under vacuum, leaving 23.4 g of a colorless amorphous residue of crude diacid. This material shows a maximum in the ultraviolet spectrum at 224 mp (s 6,400) indicating a 53 % yield of unsaturated acid (6). It is used without further purification. 

The application of this addition to aminomethylene ketones provides a convenient synthesis of monoamides of pimelic acid (508). It should be noted that the corresponding oxidation of hydroxy methylene cyclohexanone leads to ring contraction and formation of cyclopentanoic acid. 

The ether extract is evaporated to dryness to give about 500 mg of a crude product. From the ether solution there is obtained about 290 mg of yellow crystals, MP 220° to 236°C which is 17a,20,20,21-bis(methylenedioxy)-11 (3-formyloxy-2-hydroxy-methylene-6,16a-di-methyl-4,6-pregnadiene-3-one. The analytical sample is recrystallized from ethyl acetate and has a melting point of 249° to 255°C, [oIq -217°, I R 5.81 and 8.37 ji. From the mother liquor is obtained about 127 mg of 17a,20,20-21-bis(methylenedioxy)-11(3-hydroxy-2-hydroxymethylene-6,16a-dimethyl-4,6-pregnadiene-3-one. The analytical sample is recrystallized from ether and has a melting point of 200° to 204°C, [alo -197°, IR 6.05 to 6.2 and 6.4 jd. 

The 17tt,20,20,21-bis(methylenedioxy )-11 (3-hydroxy-2-hydroxy methylene-6,16a-dimethyl-4,6-pregnadiene-3-one (1.19 g) is dissolved In 25 cc of ethanol. 300 mg of phenyl hydrazine is added and the mixture is refluxed under nitrogen for one hour. About 25 cc of water is added. The product is then extracted into 150 cc of ether. The extracts are washed with 2N HCI, with saturated sodium bicarbonate, water and saturated sodium chloride solution, and then dried over sodium sulfate and evaporated to dryness to give about 1.2 g... 

A somewhat related sequence leads to trilostane (111), a compound that inhibits the adrenal gland more specifically the agent blocks some of the metabolic responses elicited by the adrenal hormone ACTH in experimental animals. Reaction of the hydroxy-methylene derivative 108, obtained from testosterone, with hydroxylamine gives the corresponding isoxazole (109). Oxidation of the C-4,5 double bond by means... 

In the next step of the sequence, the authors sought to introduce a hydroxy-methylene substituent at the unsubstituted 7-position of the enone. This bond construction can be carried out by conducting a Baylis-Hillman reaction with formaldehyde. In this instance, the authors used a modification of the Baylis-Hillman reaction which involves the use of a Lewis acid to activate the enone [26]. Under these conditions, the enone 42 is treated with excess paraformaldehyde in the presence of triethylphosphine (1 equiv), lanthanum triflate (5 mol%), and triethanolamine (50 mol%). It is proposed that the lanthanum triflate forms a complex with the triethanolamine. This complex is able to activate the enone toward 1,4-addition of the nucleophilic catalysts (here, triethylphosphine). In the absence of triethanolamine, the Lewis acid catalyst undergoes nonproductive complexation with the nucleophilic catalyst, leading to diminution of catalysis. Under these conditions, the hydroxymethylene derivative 37 was formed in 70 % yield. In the next step of the sequence, the authors sought to conduct a stereoselective epoxidation of the allylic... 

The procedure for the preparation of a dithiolane from a hydroxy-methylene derivative of a ketone and ethylene dithiotosylate (ethane-1,2-dithiol di-p-toluenesulfonate) can be varied to produce dithianes when the latter reagent is replaced by trimethylene dithiotosylate.8,4 The dithiotosylates also react with enamine derivatives to produce dithiaspiro compounds.4,5... 

Deprotonation provides the necessary electron push to kick out the electron pair joining C(6) with the nitrobenzene oxygen. If, however, N(l) is alkylated (as with the nucleosides and nucleotides), OH catalysis is much less efficient since it now proceeds by deprotonation from N(3) (with the uracils) or from the amino group at C(4) (with the cytosines). In these cases the area of deprotonation is separated from the reaction site by a (hydroxy)methylene group which means that the increase in electron density that results from deprotonation at N(3) is transferable to the reaction site only through the carbon skeleton (inductive effect), which is of course inefficient as compared to the electron-pair donation from N(l) (mesomeric effect) [26]. Reaction 15 is a 1 1 model for the catalytic effect of OH on the heterolysis of peroxyl radicals from pyrimidine-6-yl radicals (see Sect. 2.4). 

The synthesis of cyclic ethers 137 was achieved by a Fischer indole synthesis starting from cyclic keto arylhydrazones generated in situ from 4-(hydroxy-methylene)-3,4-dihydrobenzo[ 7]oxepin-5(2H)-one 136 and the corresponding diazonium salt (Equation (20), 1993JHC1481). 

Diazocycloalkanones with five- to twelve-membered rings can be synthesized by the present procedure in good yields (Table I).4 Diazo transfer with deformylation can also be used for the preparation of bicyclic a-diazo ketones.10,11 A related procedure involving reaction of the sodium salt of an a-(hydroxy methylene)-ketone with p-toluenesulfonyl azide in ethanol has been applied to the synthesis of diazoalkyl ketones, a-diazo aldehydes, and a-diazo carboxylic esters.12... 

Mepiquat chloride Ethyl 4-cyclopropyl(hydroxy)methylene-3,5-dioxocyclohexanecarboxylate... 

Potent inhibitors of aspartyl proteases have been prepared by incorporating hydroxy-methylene transition-state analogues modified in the a-position. The a-methylene moiety is either functionalized by a heteroatom 16,71 72 or it is dihalogenated)15,73,74 Alkyl substituents in that position are found in several residues present in compounds of natural origin, such as dolaproine (8) in dolastatin 10 and 4-amino-3-hydroxy-2-methylpentanoic acid (9) in bleomycin D (Scheme 1). This position is also substituted in synthetic, conformationally constrained six-membered-ring analogues)75 77 ... 

In a number of early papers only one isomer was said to be formed,146,159,261 but this conclusion was often incorrect and due to inadequate separation procedures. Even keto aldehydes (hydroxy-methylene ketones) tend to give two products in spite of the considerable difference between the carbonyl groups159,262 here again the earlier papers were at fault.263,264 The reactions of hydroxy-methylene acetophenone, which is particularly accessible, with... 

Dimethyl-2,3-dihydro-1,8-naphthyiidin-4(l//)-one (38) gave its 3-hydroxy-methylene derivative (39) (Et02CH, NaOEt, PhH, 20°C 81%) that underwent oxidation in refluxing benzene to afford l,7-dimethyl-4-oxo-l,4-dihydro-l,8-naphthyridine-3-carbaldehyde (40) as the main product ( 45%).1394... 

N-Hydroxy methyl 1 cyclohexene 1.2 dicarboximide tetramethrin Hydroxy methylene acrylic acid methacrifos... 

A useful modification, which prevents 2,2-diarylations, first introduces a 2-hydroxy-methylene group 92). 

Fod = 6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionata hfc = [3-(heptafluoropropyl)-hydroxy methylene] -d-camphorate. 

The hydroxy methylene complex is isomeric with complexes formed by ude-on coordination of formaldehyde, as shown in Equation (18). 

HYDROXY-2-HYDROXYMETHYLENE-17-a-METHYL-3-ANDROSTANONE 17-P-HYDROXY-2-(HYDROXY-METHYLENE)-17-METHYL-5-a-ANDROSTAN-3-ONE ... 

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