It is possible that in preparing the sodium salt of diethylbarbituric acid, the ring opens up, forming a compound not so easily affected by dilute mineral acids.
TABLE 2.—EXTRACTION OF A SAMPLE OF BARBITAL-SODIUM
| Length of Time | Diethylbarbituric Acid per Cent. | |
| a. | Immediately | 75.5 |
| a1. | 3⁄4 hour | 82.0 |
| b. | Immediately | 82.0 |
| c. | 11⁄2 hours | 80.5 |
| d. | 4 hours | 82.82 |
| e. | 4 hours | 83.56 |
| f. | 4 hours | 83.41 |
| g. | 451⁄2 hours | 84.89 |
| h. | 451⁄2 hours | 84.73 |
| Theory | ....... | 89.31 |
| Veronal-Sodium | (Puckner and Hilpert) | 89.01 (average) |
| Medinal | (Puckner and Hilpert) | 88.95 (average) |
PHENETIDYL-ACETPHENETIDIN HYDROCHLORID[230] (HOLOCAIN HYDROCHLORID)
Phenetidyl-acetphenetidin hydrochlorid was introduced in the United States under the name of “holocain hydrochloride” by Farbwerke, vorm Meister Lucius and Bruening, Hoechst a. M. Germany; the product apparently had not been patented in this country, although it was protected in Germany under patents No. 78868 and 80568. New and Nonofficial Remedies, 1918, describes “holocain hydrochlorid” as ethenyl-paradiethoxy-diphenyl-amidin hydrochlorid CH3:(NC6H4OC2H5)(NHC6H4OC2H5)HCl. It is used as a local anesthetic for the eye.
The standards, such as had been described, were meager and unsatisfactory. Hence when the first specimen of American-made phenetidyl-acetphenetidin was sent to the A. M. A. Chemical Laboratory through the agency of the Federal Trade Commission and the Committee on Synthetic Drugs, it was necessary for the laboratory to work out adequate standards.[231] As a result of the chemical work, a rather comprehensive monograph was drawn up, which was published in the 1918 Laboratory Reports. A summary of the products examined, with some of the chemical data, is given in Table 3. It will be seen that one specimen had a deficiency of about 2 per cent. of free base.
TABLE 3.—DATA ON PHENETIDYL-ACETPHENETIDIN HYDROCHLORID
| Manufacturer | Appearance | Moisture | Melting Point | Phosphorus Compounds | Phenetidin* | Indol Reaction | Ash | Per Cent. Base by Weight | Per Cent. Base by Titration | Melting Point of Base | Per Cent. Platinum in Platinum Salt + |
| John T. Milliken Co. | White crystalline powder | 5.13 | 191.5 to 192 | Absent | Negative | Positive | 0.00 | 89.16 | 89.16 | 116 to 117 | 19.02 |
| Synthetic Products Co. | White crystalline powder | 2.90 | 192 to 192.5 | Absent | Negative | Positive | 0.13 | 87.49 | 87.26 | 116 to 117 | 19.3 |
| H. A. Metz Laboratories, Inc. | White crystalline powder | 4.99 | 192 to 192.5 | Absent | Negative | Positive | 0.00 | 89.14 | 88.55 | 117 | 19.34 |
| Farbwerke-Hoechst Co. (German specimen) | Slightly pink crystal | 5.09 | 190 to 191 | Absent | Negative | Positive | 0.16 | 89.65 | 89.64 | 116 to 117 | 19.00 |
* The phenetidin test is not very sensitive.
The melting point of the free base is given by a number of writers at 121 C. Although Kennert[232] stated it to be 117 C. and not 121 C., his findings seemingly went unheeded. It will be noted that our work shows the melting point to be in accord with that announced by Kennert.