The Preparation of 21-Fluorosteroids

Tannhauser, Pia; Pratt, Richard J.; Jensen, Elwood V.

doi:10.1021/ja01592a104

Cited by 33 publications

(7 citation statements)

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“…In confirmation of the indications by Tannhauser et al (1) we found 21-fluoroprogesterone to possess approximately three times the luteoid activity of progesterone. 2 On the other hand, even at doses of 3.5 mg. per animal (10 /x-moles) 21-chloroprogesterone showed no appreciable action on the uterus of the estrogen primed virgin rabbit.…”

Section: Resultssupporting

confidence: 88%

Concerning the Progestational Activity of 21-Hal0genated Progesterones1

Engel

Noble

1957

Endocrinology

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Section: Resultssupporting

confidence: 88%

Concerning the Progestational Activity of 21-Hal0genated Progesterones1

Engel

Noble

1957

Endocrinology

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“…Nevertheless, it is still occasionally used because it requires very mild conditions. It is especially suited for the replacement of a-halogens in ketones, particularly in steroid chemistry [113,114). Both mercurous and mercuric fluorides are used for substituting fluorine for halogens.…”

Section: Replacement By Means Of Hydrogen Fluoridementioning

confidence: 99%

Organic Fluorine Chemistry

Hudlický

1971

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“…The crude product was distilled in uucuo to give (7) General Procedure for Dehalogenation of a-Halogeno Ketones (Table I). data and were confirmed by the fact that (21) and (23) are known compounds. After being stirred under the conditions described in Table 1, the reaction mixture was poured into ice-water, and the mixture was extracted with dichloromethane.…”

Section: (5)'mentioning

confidence: 60%

“…The ether solution was shaken with dilute HCl, and the organic layer was washed with aqueous Na,CO, and brine and dried (Na,SO,). The dithioacetals (15) Compounds (21) and (23). -To a stirred and ice-cooled solution of the ahalogeno ketone (1 mmol) in dry dichloromethane (2 ml, MeOH-free) under nitrogen were added aluminium chloride (1.5 mmol) and ethanethiol or diethyl sulphide (0.4 ml).…”

Section: (5)'mentioning

confidence: 99%

Hard acid and soft nucleophile systems. Part 11. Hard-soft affinity inversion: dehalogenation of α-halogeno ketones with aluminium chloride and a thiol

Fuji¹,

Node²,

Kawabata³

et al. 1987

J. Chem. Soc., Perkin Trans. 1

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x-Halogeno ketones have been dehalogenated with a combination of aluminium chloride and ethanethiol. The mechanism involved in deiodination and debromination differs from that of dechlorination and defluorination. A hard-hard interaction between carbonyl oxygen and aluminium chloride and a soft-soft interaction between iodine or bromine and thiol are the dominant factors for direct deiodination and debromination. In dechlorination and defluorination there is initial formation of the corresponding dithioacetal, whereby hard carbonyl oxygen is replaced by the soft sulphur atom.x-Chloro-and a-fluoro-dithioacetals then undergo dehalogenation to afford vinyl sulphide as a result both of a favourable soft-soft interaction between the sulphur atoms in the dithioacetal entity and thiol, and also a favourable hard-hard interaction between the nucleophilic chlorine or fluorine and aluminium chloride. a-Chloro-and a-fluoro-benzyl benzyl ketones afforded the dehalogenated product with concomitant lr2-transposition of the carbonyl group. This suggests that there is an indirect path which operates competitively via a 1,2-dithio-olefin from a-halogenodithioacetals to vinyl sulphide. Addition of thiol to vinyl sulphide leads to the final product. A concept of hard-soft affinity inversion is proposed.Systems consisting of a hard acid and a soft nucleophile have been utilized for the cleavage of a variety of chemical bonds. Aluminium chloride-ethanethiol is such a system and this has been successfully utilized for the cleavage of bonds including C-0,*s3 C-S? C-NO,,S C=C,6 and C -h a l~g e n .~ We found that the same combination effected dehalogenation of Xhalogeno ketones to give the dithioacetal of the corresponding ketones.' Since many practically useful methods for dehalogenation of x-halogeno ketones have been r e p~r t e d ,~ the present method is merely a complement from a synthetic point of view. However, as will be discussed, the mechanism involved in dechlorination and defluorination with this combination is completely different from that of debromination and deiodination. In x-bromo or a-iodo ketones, carbonyl oxygen and halogens are regarded as a hard centre and a soft centre, respectively. Thus, a pertinent combination of a hard acid and a soft nucleophile can be used for dehalogenation of a-bromo and Xiodo ketones as shown in Figure 1. A number of systems have been developed for this type of transf~rmation.~ On the other hand, since chlorine and fluorine are relatively harder than bromine and iodine, a soft nucleophile will encounter greater difficulty in attacking the halogen atom. According to the hard and soft acids and bases (HASB) principle, the electron movement shown in Figure 2, the reverse of that shown in Figure 1, is expected when the hard carbonyl oxygen is replaced by sulphur which is regarded as a soft atom. Thus, the transformation of an r-chloro or r-fluoro ketone into the corresponding dithioacetal results in the reversal of hard-soft dissymmetry as well as charge dissymmetry. The details of this type...

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The Preparation of 21-Fluorosteroids

Cited by 33 publications

References 0 publications

Concerning the Progestational Activity of 21-Hal0genated Progesterones1

Concerning the Progestational Activity of 21-Hal0genated Progesterones1

Organic Fluorine Chemistry

Hard acid and soft nucleophile systems. Part 11. Hard-soft affinity inversion: dehalogenation of α-halogeno ketones with aluminium chloride and a thiol

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