Steroids formyl deriv

Formyl derivatives are also popular in situations where several groups have to be blocked, as in steroid analysis, because the formyl group adds little to the molecular weight. To prevent the formation of artifacts, the strength of the formic acid should be kept at 95% and reaction allowed to take place for 30 min at... 

The oxidation of steroidal 3a-, 3)5-, 20a-, and 20j8-amines with m-chloroper-benzoic acid to the corresponding nitro-compounds has been described. Oxidation of several steroidal tertiary amines with chromic acid in pyridine leads to the corresponding N-formyl derivatives. Photosensitised irradiation (methylene blue) of 20a- and 3)5-dimethylamino-steroids leads to a secondary amine in 80% yield. The formyl derivative (10% yield) is not an intermediate in the N-demethylation reaction. 3a-Dimethylamino-5a-pregnane gives 5a-pregnan-3-one and the secondary amine. Conanine gives the lactam (50). ... 

The compounds (Table 4) in the column headed Aldehyde are A-nor- or B-nor-5)5-formyl derivatives (e.g. 574), resulting from ring contraction. The normal steroid skeleton (576) is regenerated if the aldehyde (574) is first reduced, and the tosylate (575) of the resulting neopentyl alcohol then solvolysed. ... 

Fused Heterocycles The /8-dicarbonyl system in the formyl derivative of 17-methyltestosterone shows much the same reactivity as the same array in simpler compounds. Thus, reaction of the formyl derivative 17-1 with hydrazine fuses apyrazolering onto the steroid at positions 2,3 (21-1) (Scheme 5.21). This compound, stanazol, is one of the more frequently abused anabolic agents. Reaction of the same formyl derivative with hydroxylamine goes on to add an isoxazole ring to give danazol (21-2). 

A number of nitrogen heterocycles have been prepared from solasod-4-en-3-one (8) in a search for new physiologically active steroids. Reaction of (8) with ethyl formate and sodium hydride gave the formyl derivative (9), which cyclized with methylhydrazine, phenylhydrazine, and p-nitrophenylhydrazine to give the pyrazoles (11), (12), and (13), respectively. Similarly, (8) was condensed with ethyl trifluoroacetate to give (10), which reacted with hydrazine and with hydroxylamine to give pyrazole (14) and isoxazole (16), respectively. Heterocycles (15) and (17)... 

Making a formyl derivative adds only 28 to the molecular weight of a compound, and for this reason has found particular favour in situations where several groups have to be blocked, such as in steroid chemistry, where the formyl derivatives appeared to be among the most suitable for the analysis of steroids by gas chromatography. However, it must be said that formyl derivatives are not necessarily the most volatile some of the per-fluoroacyl or methoxycarbonyl derivatives may be more volatile than the corresponding formyl ones. 

Formyl derivatives are also popular in situations where several groups have to be blocked, as in steroid analysis, because the formyl group adds little to the molecular weight. To prevent the formation of artifacts, the strength of the formic acid should be kept at 95% and reaction allowed to take place for 30 min at 40°C. Alternatively, sodium formate can be used, an example of which is in the preparation of the enol rert-butyldi-methylsilyl derivatives of steroids and bile acids. Sodium formate solution (1 mg in 100 p,l) is dried under a stream of nitrogen in a 1 ml reaction tube fitted with a Teflon-lined screw cap. The tube is then heated to 270°C for 30 min, cooled, and 10 p,g of the steroid in 100 p,l of methanol added. The solvent is evaporated under a stream... 

Stanozol Stanozol, 17a-methyl-5a-androstano[3,2-c]pyrazol-17j3-ol (29.3.13), is made by reducing the double bond at C4-C5 in methyltestosterone, which has independent interest as an anabolic drug of mestanolone (29.3.11). Mestanolone undergoes formylation with ethylformate in the presence of sodium ethoxide, forming a 2-formyl (oxymethylene) derivative (29.3.12), which upon reaction with hydrazine easily cyclizes to the desired stanazole (29.3.13), which is a pyrazol-condensed steroid system [33,34]. 

Peracid oxidation of the D-homo-oestrone derivative (59) gave the C-ring aromatic compound (60). ° Mono- or tri-formylation with DMF-POCI3 of 17-methylene-steroids led to the unsaturated aldehydes (61) or the dimethylamino-bisaldehydes (62) which were readily converted with NHa-EtOH into the heterocycles (63). 14-Azidopregnanes are available from the reactions of A -... 

An efficient synthesis of 1,4-oxazepines has been developed based on iodine-sodium bicarbonate-promoted intramolecular cyclisation of the enamides 237, which were derived in turn from the p-formyl enamides 236 by sodium borohydride reduction. Reductive removal of the iodo-substituent in 238 was readily achieved using sodium sulfite. The R1 and R2 groups were part of a ring system, for example a steroid system [01SC3281],... 

Enamines may be reduced by sodium borohydride to give saturated amines, but only if a protonating species is available to convert the enamine initially into the iminium cation (lo). Steroidal g-amino-g,5-dienes are unreactive to sodium boro-hydride alone, but addition of acetic acid leads to rapid reduction via the iminium ion (10) to give gj -amino-A -steroids [224], The possibility that diborane was the reactive species in the NaBHd/HOAc system was excluded by the virtual non-reactivity of the enamine to externally generated diborane. Reduction of the iminium ion derivative (3) of a 6-formyl enol ether has been exploited in a variant of the Vilsmeier synthesis of 6-methyl steroids [22 ], the reduction product was the 6-aminomethyl enol ether (ii) which suffered hydrogenolysis with Raney nickel to give the 6-methylated enol ether (12). 

Reaction of 17/J-acetoxy-la,2oc-epoxy-lj3-methyl-5a-androstan-3-one (224) with acid gave an isomeric mixture of A-nor-2-oxo-steroids (225) carrying a formyl group at C(l). Treatment of this mixture with base provided exclusively the l/ -methyl-A-nor-steroid (226).The 3a-methyl-A-norandrostane derivative (230) has been prepared as shown in Scheme 16, i.e. by oxidative cleavage of ring A of the 3-keto-derivative (227) followed by Dieckmann condensation of the diester (228), and methylation and decarboxylation of (229). - ... 

However, two examples of aldehydes that did not foUow this general rule were described in the early studies. The first example of an ODPM reaction in a P,y-unsaturated aldehyde was observed by Schaffner et al." in the direct and triplet-sensitized irradiation of the steroidal aldehyde 12 that gives the alkene 13 resulting from decarbonylation, and two other compounds, 14 and 15, derived from the ODPM rearrangement and the 1,3-formyl migration, respectively (Scheme 1). 

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