Methyl compounds, reduction carboxylic esters

Phosphorus-containing compounds provide useful substrates for ozonolysis reactions as well and can provide several products depending on the reaction workup. Several biological uses exist for -amino-a-hydroxy phosphonic acid derivatives and they can be readily prepared by ozonolysis of Al-(ethoxycarbonyl)-/3-amino-Q -methylene phosphonic esters after reductive workup with sodium borohydride (eq 54). When the reaction mixture is treated with sodium hydroxide in MeOH, an anomalous ozonolysis reaction occurs and cleavage of the methylene as well as the carbon-phosphorus bond occurs to yield (V-(ethoxycarbonyl)-a-amino methyl carboxylic esters. 

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

The first conversion of protoberberines to phthalideisoquinoline alkaloids was achieved by Moniot and Shamma (88,89). 8-Methoxyberberinephenol-betaine (131), derived from berberine (15) (Section III,B,2), is an attractive compound having a carboxyl group masked as an imino ether in ring B. The masking was uncovered by hydration with water-saturated ether to furnish dehydronorhydrastine methyl ester (367) (Scheme 65). On N-methylation (68%) and subsequent sodium borohydride reduction (90%), 367 provided (+ )-/ -hydrastine (368) and ( )-a-hydrastine (369) in a 2 1 ratio. Compound 367 was converted to dehydrohydrastine (370), which also afforded 368 and 369 by catalytic hydrogenation. 

CHEC-II(1996) <1996CHEC-II(8)345> covered a range of reactions of substituents, including hydrolyses of esters to carboxylic acids and geminal dihalides to aldehydes, reduction of aldehydes and halogens directly attached to the ring, O-methylation with diazomethane, and reduction of nitroso compounds. A selection of reactions which have... 

The resistance of the furoxan ring to chemical attack allows derivatives to be prepared via the reactions of the substituents (Section 4.22.3.4). Carboxylic acids are available by permanganate oxidation of methyl derivatives or by hydrolysis of the corresponding esters reaction with ammonia affords carboxamides. Acylfuroxans provide a source of hydroxyalkyl compounds by reduction, and oximes, for example, via nucleophilic addition. Acylation and oxidation of aminofuroxans allows the amide and nitro derivatives to be prepared. Nucleophilic displacements of nitro substituents can take place, but can be somewhat hazardous on account of the explosive nature of these compounds. Alkoxy derivatives are formed with sodium alkoxide, while reaction with thiolate anions yields sulfides, from which sulfones can be synthesized by peracid oxidation. Nitrofuroxans have also been reduced to... 

The preparation of protected (/ )-2-methyl-cysteine by Fukuyama starts with the enantio-selective discrimination of the prochiral ester groups in 6 with pig liver esterase (Scheme 3) [5]. The ester function of the resulting product 7 is selectively reduced (7 16). Cyclization to the )9-lactone gives compound 17. Attack of the thioacetate at the )9-lactone methylene carbon atom provides the (/f)-compound 18. Selective reduction of the carboxylic acid function in 7 gives the (S)-compound 19 in an analogous fashion. 

Selenolate 1 [1,2], prepared from diphenyl diselenide by reduction with NaBH4 in ethanol, is not reactive enough towards esters and lactones. However, application of more rigorous conditions, i. e. at 110-120 °C in dry DMF for lactones 15, affords the corresponding ring-opened products, cu-phenylselenyl carboxylic acids 16, in good yields [44]. Compounds 16 can be easily converted to co-ole-finic methyl esters 17 by treatment with diazomethane followed by oxidative elimination of the phenylseleno group (Scheme 25). By contrast, the uncomplex-... 

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