US963254A - Phenol sulfonate of opium alkaloids. - Google Patents

Description

GEORGE LUDWIG SCI-IAEFER, OF BROOKLYN, NEW YORK.

PI-IENOL SULFONATE OF OPIUM ALKALOIDS.

No Drawing.

Specification of Letters Patent.

Patented July 5, 1910.

Application filed May 11, 1908. Serial No. 432,233.

To all whom it may concern:

Be it known that I, GEORGE L. SGHAEFER, a citizen of the United States, residing at Brooklyn, in the county of Kings and State of New York, have invented certain new and useful Improvements in Phenol Sulfonates of Opium Alkaloids, of which the following is a specification.

This invention relates to new chemical compounds intended more especially for use as medicinal remedies and it relates more particularly to a compound for remedial purposes wherein a sulfonic acid is employed in connection with an alkaloid, presently to be described and defined in the claims.

It is well known that phenol and some of the derivatives thereof, such as guaiacol,creosote, as well as other derivatives thereof, have a very strong corrosive and caustic action or effect upon the mucous membranes and have a very unpleasant taste, rendering them, in view of that fact, objectionable for medicinal purposes. To overcome the objectionable properties of such phenols or derivatives thereof, various substances have been produced, as an instance of which is the sulfonic acid thereof which has been combined with organic or other suitable bases. I11 U. S. Letters Patent No. 579,898, dated March 30, 1897 and issued to myself, I have described a chemical compound possessing the characteristics of a compound relieved of the objectionable caustic and corrosive qualities of the phenol and its de-- rivatives. In that patent I have described a compound for medicinal purposes wherein guaiacol sulfonic acid is used in connection with an alkaloid of the cinchona group, preferably quinin. The combination or chemical compounds of guaiacol sulfonic acid and cinchona alkaloids described in said patent are amorphous and not crystallizable, as are also the salts of most of the other known alkaloids. So far as I am advised, no crystallizable salts of the alkaloids and sulfonic acid derivatives, such as guaiacol or creosote sulfonic acids, has ever been known or produced. I have, however, discovered that some alkaloids existing in opium or derivatives thereof, such as morphin, methyl-morphin, ethyl morphin, meconin and others, form crystallizable compounds with guaiacol sulfonic acid and creosote sulfonic acid. These salts are produced as neutral salts so that, for instance, the salts of the ortho guaiacol sulfonic acid with codein which may serve as typical for this purpose, would have the following formula, codein being the preferred type of the said alkaloids and the ortho guaiacol sulfonic acid the preferred type of the various existing guaiacol sulfonic acids in the general composition of the compounds herein referred to:

1. For the neutral salt:

Creosote sulfonic acid forms salt of a similar but not quite definite chemical formula, creosote being not a distinct chemical compound. To produce these salts, I make, for instance, the ortho guaiacol sulfonic acid in the usual way, by treating guaiacol with concentrated sulfuric acid, adding to the suitably diluted product, hydrate of barium, 0Xid of lead, or any other suitable base, to remove the excess of sulfuric acid, then filtering off the insoluble material, leaving a mixture of various guaiacol sulfonic acids in solution which is neutralized by a metallic base, such as hydrates or carbonates of potassium, barium, calcium, etc., whereby a solution of the respective guaiacol sulfonates is formed. This solution is then evaporated, leaving an impure product, from which the pure salt of the ortho guaiacol sulfonic acid can be obtained by recrystallization. From this salt a codein compound may be produced by double decomposition of molecular weights between a salt of codein, such as muriate, acetate, prosphate and others, and a compound of the ortho guaiacol sulfonic acid, such as barium, potassium, calcium saltor any other suitable salt, or it may be produced by dissolving the free base of the codein in a corresponding molecular quantity of the diluted ortho guaiacol sulfonic acid. The codein salt thus obtained can be purified by crystallizing the same from water, alcohol or any other suitable solvent. The pure salt forms white orthorhombic crystals or a white crystalline powder. Itis easily soluble in hot water but less so in cold water. It is sparingly soluble in strong alcohol, more freely soluble in methyl alcohol and diluted alcohol. The watery solution gives the characteristic reaction for guaiacol with ferric chlorid.

The compound forming, above stated, a crystalline substance possessing the chemical properties of the ortho sulfonic acid of the guaiacol, as well as of codein, is very useful for medicinal purposes, free from caustic effects and objectionable odors, and can be administered in the same quantities as the officinal codein salts. The compound possesses also the powerful medicinal properties of both the guaiacol and the alkaloid. While I have specifically referred to codein, other derivatives of the opium group ma be employed to an advanta e, if desirec also any other guaiacol sulfon1c acid in place of the ortho acid may be used. I, however, find that a compound comprising codein and ortho guaiacol sulfonic acid is, as a remedy, very useful for treating the mucous membranes. It is to be understood that creosote sulfonic acid may be employed in lieu of the guaiacol sulfonic acid in some cases, if found desirable.

The neutral salt of guaiacol sulfonic acid and codein contains in 100 parts 59.44 alkaloid codein (which is the equivalent of 63.20 alkaloid codein U. S. P.) and 40.56 guaiacol sulfonic acid. Both are the neutral salts and true chemical compounds. The melting point of the ortho-guaiacol sulfonate of codein is 16t165 G. This salt can be identified by adding a drop of ferric chlorid solution to the cold saturated solution of the salt, whereby the characteristic blue color indicates guaiacol sulfonic acid. If the salt is dissolved in hot water 1 :10 quickly cooled to prevent crystallization and precipitated by a very slight excess of caustic potash, the resulting precipitate will respond to the requirements of the U. S. P. for codein alkaloid. The liquor contains ortho guaiacol sulfonate of potash and if carefully neutralized with diluted sulfuric acid yields the characteristic guaiacol reaction with ferric chlorid. The compound of creosote sulfonic acid and codein has a lower, but not distinct melting point, creosote being a mixture of phenols, not being of a definite chemical composition or formula. This codein compound also differs from the ortho guaiacol sulfonate of codein by its greater solubility. As to quantities of materials to produce these salts I used in the specification molecular weights, that is for instance: 1. 1 molecular weight of acetate of codein or 374.5 parts is dissolved in boiling water 2000 parts and to this a hot solution of 1 molecular weight (or a slight excess) or about 241 parts of ortho guaiacol sulfonate of potash in 1000 parts of water is added to produce the codein salt by double decomposition. 2. If free guaiacol sulfonic acid is used: 1 molecular weight or 315 parts of codein alkaloid are dissolved in 1200 parts of hot alcohol and this solution neutralized with diluted (about 50: 1.) guaiacol sulfonic acid to a slightly acid reaction, requiring about A06 parts of this diluted acid, equal to 1 molecular weight or 203 parts of the pure ortho guaiacol sulfonic acid.

The equations of the reactions involved are as follows:

2. C H (OH)OOH3.SO3H+C18H NO Gualacol sulfonic acid. Codein.

Cr,H (OH)OCH .SO H.O gH2 NO3 Guaiacol sulfonate of codein.

potash.

C5H= OH)OCH .SO;;H.C BHQ NO +KCZH O2 Guaiacol sulfonate of codein. POCZLtSSIUIII ace ate.

About the same percentage of codein is contained in the salts formed with creosote sulfonic acid.

Having thus described the invention, what I claim as new, and desire to secure by Letters Patent, is:

1. A chemical compound being a neutral salt, a derivative of an alkaloid base of opium, and a sulfonic acid of a phenol, said salt being of a white crystalline character and being soluble in water, a solution of the salt reacting with an excess of caustic potash to precipitate the corresponding alkaloid.

2. A chemical compound being a neutral salt resulting from a morphin derivative and guaiacol sulfonic acid, the solution of the salt reacting withan excess of caustic potash to precipitate the corresponding alkaloid.

3. A White neutral salt crystalline in character derived from one molecular weight of codein and one molecular weight of guaiacol sulfonic acid, said salt having a melting point of 164:165 C. and a solution of the salt showing a blue color when ferric chlorid is added thereto.

4. A white neutral salt crystalline in character derived from codein and a sulfonic acid of a phenol, said salt being soluble in water, a solution of the salt reacting with an excess of caustic potash to precipitate codein alkaloid.

In testimony whereof I aiiix my signature in presence of two witnesses.

GEORGE LUDWIG SGI-IAEFER.

lVitnesses:

ALFRED G. MANcoLD, l VILLIAM SCHAD.