On Sulphonfluoresceïn and Some of Its Derivatives

Part 1

Transcriber's Notes: Illustration has been moved so it does not break up the paragraph.

As this was a hand-written thesis, the spelling, punctuation and hyphenation is very inconsistent. The original spelling, hyphenation and punctuation have been left unchanged.

Subscripts appears as _{X} where X is an integer.

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ON SULPHONFLUORESCEÏN AND SOME OF ITS DERIVATIVES.

DISSERTATION

Presented for the Degree of Doctor of Philosophy at the Johns Hopkins University

by C. Willard Hayes,

1887.

Contents. p.

Introduction 3. I Ortho-sulpho-benzoic acid. Preparation from toluene and H{2}SO{4} 7. ” ” para-nitro-toluene and H{2}SO{4} 8. Oxidation of toluene-o-sodium sulphonate 12. Preparation of Sulphinide from ” ” 14. ” ” ” by chlorsulphonic acid. 17. Conversion of sulphinide into o-sulphobenzoic acid. 25. Analysis of and crystallography of ” ” ” 28. II Sulphonfluoresceïn--previous attempts 29. Preparation and purification of s-fluoresceïn 30. Analyses of ” 34. Properties of ” 35. Salts. Ba. and Ca. of ” 37. Acetyl derivative of ” 41. Br substitution products of ” 42. Action of H{2}SO{4} on ” 44. Action of HCl on ” 45. Reduction of ” 46. Conclusion. 47.

On Sulphonfluoresceïn and some of its Derivatives.

Introduction.

The close analogy in composition and structure between phthalic acid and ortho-sulpho-benzoic acid suggests the possibility of obtaining from the latter, by its action on phenols, substances analogous to the phthaleïns. If such compounds could be made they would afford a favorable opportunity of studying the effects produced in the properties of a compound by the replacement of CO by SO_{2}. It was with a view to such study that the following discussed work was undertaken at the suggestion of Prof. Remsen and carried on under his constant guidance.

Some experiments previously performed by Remsen and Palmer (A.G.) indicated the possibility of the formation of a fluorescent substance by the action of ortho-sulpho-benzoic acid on resorcin but they did not succeed in obtaining any definite crystallized compound from the reaction.

The chief obstacle to be overcome in the work is the difficulty in obtaining the o-sulpho-benzoic acid and a large proportion of the work here described was applied in that direction.

Ortho-sulpho-benzoic acid: Methods for its preparation.

1. From toluene and H{2}SO{4}.

A method employed by Remsen and Fahlberg (Am. Ch. Jour. Vol. 1. p _ ) for getting the sulphonic acid group in the ortho position to methyl was; (a) treat toluene with fuming H{2}SO_{4} forming thus ortho- and para- toluene sulphonic acids, (b) make the calcium salt of the sulphonic acids thus formed and from this the potassium salt. (c) treat this mixture of potassium toluene sulphonates with phosphorous penta-chloride forming the corresponding sulphonchlorides. One of these (para) being a solid and the other (ortho) an oily liquid a nearly complete separation could be effected. The difficulty with this method is however that the larger part of the product is the para and only a comparatively small proportion of the ortho compound is formed.

2. From p-nitro-toluene and H{2}SO{4}.

A second method employed consists in starting with p-nitro-toluene. This when treated with H{2}SO{4} forms toluene p-nitro o-sulphonic acid. If now a method could be obtained for removing the nitro group the desired result would be attained.

The attempt was made by Remsen and Palmer (A.G.) to accomplish this by (a) reducing the nitro compound to the amide, (b) making the diazo compound and (c) boiling this with absolute alcohol. According to generally accepted views this should effect the removal of the diazo group and its replacement by hydrogen.

Experiments however showed that the replacement was made not by hydrogen but by the ethoxy group -OC{2}H{5}. This method was therefore impracticable.

A modification of this method was suggested by an observation of Baeyer and Liebermann that if phenyl hydrazine be boiled with a dilute solution of copper sulphate the hydrazine group is replaced by hydrogen and benzene thus formed. Hence it was believed that if the hydrazine compound should be made from diazo compound mentioned above, the corresponding hydrocarbon, i.e. toluene o-sulphonic acid could be obtained. The results of experiments showed that this afforded a practicable method of preparing toluene ortho-sulphonic acid.

After experimenting with various modifications of the method the following was found to be the best adapted to the purpose.

The potassium salt of toluene p-nitro-o-sulphonic acid is easily obtained, as already stated, by heating p-nitro toluene on the water bath with three times its weight of fuming H{2}SO{4}, neutralizing with chalk and to the solution of calcium salt thus obtained adding a slight excess of K{2}CO{3}. On filtering from. the precipitated CaCO_{3} and evaporating slightly, the salt is obtained in long needle shaped crystals of a pale straw yellow color. This is

┌─ │CH{3} C{6}H{3}┤SO{2}OH (o) │NO_{2} (p). └─

The reduction of the nitro group is best effected by means of tin and HCl, in the proportion, salt 5 parts, tin 6 parts and concentrated HCl 30 parts.

Part 2

The amido acid forms a compound with tin which crystallizes from the HCl together with stannous chloride. This compound may be broken up and the tin removed by continued boiling with water.

A better method of removing the tin is by dissolving the compound in Na{2}CO{3}. This forms a salt with the amido acid and throws down the tin as Sn(OH)_{2}, a white flocculent precipitate. On filtering and adding to the solution conc. HCl, the free amido acid is deposited in characteristic colorless, rhombic crystals, having the formula

┌─ │CH{3} C{6}H{3}┤SO{2}OH (o) │NH_{2} (p) └─

The method at first employed for preparing the hydrazine compound consisted in treating the amido acid, suspended in HCl, with potassium nitrite and then with stannous chloride. The tin was then removed from the solution by the addition of sodium carbonate and the hydrazine compound thrown down with HCl. This method however gave poor results the yield being only about 50% of the theoretical.

Another method was accordingly substituted for the above, namely that of Strecker and Römer (Ber. IV. s 784.) By this the diazo compound is made first and isolated. This is done by suspending the finely powdered acid in absolute alcohol, cooling and passing a current of the oxides of nitrogen through in the ordinary way. The acid changes in appearance, becoming more crystalline and slightly darker and settles quickly on being shaken. The reaction here may be expressed thus--

┌─ ┌─ │ CH{3} │ CH{3} C{6}H{3} ┤ SO{2}OH + HNO{2} = C{6}H{3} ┤ SO{3} + 2H{2}O │ NH_{2} │ \ └─ │ N=N └─

When the reaction is completed as shown by the appearance of the suspended powder it is filtered and while still fresh is added to a solution of acid sodium sulphite as long as it continues to dissolve readily.

To this solution there is added a quantity of solution of acid sodium sulphite equivalent to that already used and the solution is then boiled. It has at first a deep red color but in a few moments becomes light reddish yellow. The reaction of HNaSO_{3} on the diazo compound may be represented in two stages, the first portion forming an addition product and the second acting as a reducing agent. Thus,

┌─ ┌─ │ CH{3} │ CH{3} 1. C{6}H{3} ┤ SO{3} + HNaSO{3} = C{6}H{3}┤ SO{2}ONa │ \ │ │ N═N │ N═NSO{3}H └─ └─ ┌─ │ CH{3} 2. C{6}H{3} ┤ SO{2}ONa + HNaSO{3} + H{2}O │ N═NSO{3}H └─ ┌─ │ CH{3} = C{6}H{3} ┤ SO{2}ONa + HNaSO{4}. │ NH-NHSO_{3}H └─

To the hot solution an excess of conc. HCl is added when the hydrazine compound separates in a few moments in lustrous yellow scales which completely fill the solution. On the addition of the HCl a large amount of SO{2} is given off from the excess of HNaSO{3} and the solution becomes deep red. When the hydrazine has separated the mother liquor is again yellow.

The reaction is represented as follows:

┌─ │CH{3} C{6}H{6}┤SO{2}ONa + HCl + H{2}O │NH-NHSO{3}H └─ ┌─ │CH{3} = C{6}H{3}┤SO{2}OH + H{2}SO{4} + NaCl │NH-NH_{2} └─

The yield of hydrazine when both the diazo and the NaHSO_{3} are freshly prepared is practically quantitative.

The hydrazine thus prepared was treated with a hot 10% solution of copper sulphate till a permanent blue color was obtained in the solution. Nitrogen is evolved and the copper sulphate is reduced to cuprous oxide which is precipitated as a red powder. The reaction is as follows.

┌─ │CH{3} C{6}H{3}┤SO{2}OH + 2CuSO{4} + H{2}O │NH-NH{2} └─ ┌─ = C{6}H{4}┤CH{3} + Cu{2}O + N{2} + 2H{2}SO{4} │SO_{2}OH └─

Chalk was added to the solution to precipitate the H{2}SO{4} and form a calcium salt of toluene-o-sulphonic acid. From this the sodium salt was made by adding a slight excess of Na{2}SO{3} and evaporating to dryness. The salt is very soluble being deliquescent in the air while the corresponding potassium salt is not. From 1538 gr. of para-nitro-toluene, 655 gr. of toluene ortho-sodium sulphonate were obtained.

Having thus obtained the toluene ortho-sulphonic acid the next step in the problem was to find a convenient method for converting this into ortho-sulph-benzoic acid. Two ways present themselves for accomplishing this end. (1) direct oxidation of this salt and (2) conversion into benzoic sulphinide from which the acid may be obtained. Both of these methods were tried.

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