S 43. The synthesis of thyroxine and related substances. Part II. The preparation of dinitrodiphenyl ethers

Borrows, E. T.; Clayton, J.C.; Hems, B. A.; Long, A. G.

doi:10.1039/jr949000s190

Cited by 28 publications

(26 citation statements)

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“…When cool, the solution deposited pale yellow needles which after four recrystallizations from aqueous ethanol gave the colorless analytical sample 1n.p. 149-150' (k Methyl 4-chloro-3,5-dinitrobenzoate (2.6 g) (15) in dry benzene (20 ml) was treated with dry pyridine (1.5 1111). After 1 hour the slightly sticky yellow crystals were recovered, washed with benzene and then with acetone, dissolved in warm ethanol, and reprecipitated with ether to give white prisins (3.0 g, 88%), n1.p.…”

Section: Dimorphism Of Ii1b!ethyl 2 -( 6 ' --L M I N O -4 ' -C a R B mentioning

confidence: 99%

Synthesis, Reactions, and Properties of Some Highly Hindered Diphenyl Ethers

Allen¹,

Moir²

1959

Can. J. Chem.

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In the Hems synthesis of diphenyl ethers, an ortho-carbonyl offered less obstruction when held in a lactone ring than when present as an ester. Side reactions interfered with the Hems synthesis of highly hindered diphenyl ethers, and the highly hindered, high1.y activated ethers produced in the synthesis were easily cleaved by nucleophilic reagents, often in a few minutes a t room temperature. The latter fact added a lively interest to the transformation of the ethers into other derivatives. Three of these were of special interest: ( a ) methyl 2-(6'-amino-4'-carbomethosy-2'-nitrophenosy)benzoate ( V l c ) which existed in remarltably stable dimorphic forms, ( b ) the dibenzosazepine V I I I , and ( c ) the quadruply orthosubstituted, asymmetrical 7-(4'-carbomethoxy-6'-laevo-menthosyacetamino -2'-nitrophenoxy)metameconine ( I X ) .

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Section: Dimorphism Of Ii1b!ethyl 2 -( 6 ' --L M I N O -4 ' -C a R B mentioning

confidence: 99%

Synthesis, Reactions, and Properties of Some Highly Hindered Diphenyl Ethers

Allen¹,

Moir²

1959

Can. J. Chem.

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“…Thompson et aL., 1933;Monroe and Turner, 1949). We have shown in a previous communication (Clayton, Free, Page, Somers, and Woollett, 1949), using thyroxine sodium labelled with '"'I, that absorption of this salt from the intestine does occur, but these studies have not been extended to free thyroxine itself.…”

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“…We compared the activity of L-thyroxine sodium, synthesized by the method of Chalmers, Dickson, Elks, and Hems (1949) [(a) = -5.7°in ethanol and N-sodium hydroxide (2: 1)] with standard DL-thyroxine sodium (Borrows, Clayton, and Hems, 1949). By the subcutaneous route we found the L-isomer to be twice as active as the DL-mixture (Table VI) and closely similar results were obtained from oral administration, in accord with the findings of Foster, Palmer, and Leland (1936) and of Reineke andTurner (1943 and1945).…”

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“…As standard throughout we have used the pure sodium salt of synthetic DL-thyroxine (Borrows, Clayton, and Hems, 1949 Table. Of all compounds examined, the most active was the mono-sodium salt of thyroxine. No correlation was evident between the solubilities of the derivatives and their activities, with the possible exception of free thyroxine and its mono-sodium salt.…”

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“…For this purpose a number of preparations of synthetic thyroxine and its derivatives were prepared (Clayton and Hems, 1949) and examined for thyroid activity. This paper records the results obtained biologically.…”

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Measurement of Thyroid Activity by the Mouse Anoxia Method

Basil¹,

Somers²,

Woollett³

1950

British Journal of Pharmacology and Chemotherapy

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Animals given substances with thyroid activity show a reduced resistance to anoxia (Duran, 1920), and Smith, Emmens, and Parkes (1947) have used this effect in a method of thyroid assay based on the survival times of mice in closed jars. We have used it for comparing the activities of thyroxine and some of its derivatives. We find it relatively simple to carry out; the results it gave have been confirmed in clinical trials, both with sodium thyroxine and with the N-formyl derivative (Hart and Maclagan, 1950).We were particularly interested in two questions: has solubility an important effect on the activity of thyroxine and has thyroxine enhanced activity in the dried glandular extract ? For this purpose a number of preparations of synthetic thyroxine and its derivatives were prepared (Clayton and Hems, 1949) and examined for thyroid activity. This paper records the results obtained biologically. PROCEDURE Throughout the whole of the experiment the mice were kept in a thermostatically controlled incubator room at a temperature of 25.50 ± 1°. For each experiment use was made of male fawn mice of the GFF strain, weighing between 18 and 24 grammes, distributed into groups of twenty animals to give uniform body weight representation. Usually six groups, at ascending dose levels, were employed, three for the standard and three for the test preparations; a further twenty mice were kept as controls.The doses were administered on three alternate days, every animal in a group receiving the same dose irrespective of body weight and the volume of the solution injected being the same for all groups. All compounds for assay were either suspended in 0.9 per cent sodium chloride solution or dissolved in 0.01 M-sodium carbonate solution containing 0.9 per cent sodium chloride.On the second day after the final injection the groups of ten mice were sealed in glass jars and the time of sealing was recorded. We used 32-oz. wide neck, screwcapped clear bottles, with soft paraffin smeared on the neck to ensure a complete seal. The volumes of the jars ranged from 980 to 1,020 ml., and they were randomly distributed. The time of survival was recorded for each individual mouse, the endpoint being the last visible respiration, which is almost invariably preceded by marked terminal convulsions.

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