Dihydrochloride

Trade Name Manufacturer Country Year Introduced 

L-3-Hydroxy-N-methyl-morphinan Phenyl trimethyl ammonium chloride D-Tartaric acid 

The methylation of 51.4 parts by weight of D,L-3-hydroxy-N-methyl-morphinan is carried out with a methylating solution obtained from 51.5 parts by weight of phenyl-trimethyl-ammonium-chloride. The D,L-3-methoxy-N-methyl-morphinan is isolated in the form of its hydrobromide, which melts with 1 mol of water at 92°-94°C, without water at 239°-240°C. The base isolated from the aqueous solution by means of sodium carbonate melts at 81°-83 C. 

1 parts by weight of D,L-3-methoxy-N-methyl-morphinan base are dissolved with 15.0 parts by weight of D-tartaric acid in 150 parts by volume of hot alcohol. The solution is cooled and seeded with (-h)-3-methoxy-N-methyl-morphinan-tartrate. The (-h) form which is difficultly soluble in alcohol separates, is filtered by suction and washed with a little alcohol. 

The (-h)-3-methoxy-N-methyl-morphinan-tartrate melts with 1 mol of water at 195°-196°C [alD = -h30.6° (c = 1.5 in water). The (-h) base melting at 108°-109°C may be obtained from the tartrate by means of sodium carbonate. The corresponding hydrobromide melts at 122°-124°C = -h27.6° (c = 1.5 in water). 

A solution of 50 g. of acetonedicarboxylic acid (crude, containing some sulfuric acid) [Org. Syntheses Coll. Vol. 1, 11 (1941)] in 100 ml. of water is stirred and cooled in an ice bath while a concentrated aqueous solution of 30 g. (0.44 mole) of sodium nitrite is added drop-wise. The resulting mixture is acidified by the slow addition of dilute sulfuric acid with continued cooling and stirring. The precipitated diisonitrosoacetone is collected by filtration and washed with water. The yield is about 50%. The product may be further purified by recrystallization from methanol. The pure product melts at 143-144°. 

Fifteen grams of crude diisonitrosoacetone is added in small portions over a 1-hour period to a mixture of 110 ml. of concentrated hydrochloric acid and 400 g. of stannous chloride. The temperature of the reaction mixture is held to 20-30° by occasional cooling. Another 110 ml. of concentrated hydrochloric acid is added, and this is followed by the addition of another 18 g. of diisonitrosoacetone in the same manner as before. Another 50 ml. of concentrated hydrochloric acid is added, and the mixture is cooled in the refrigerator overnight. The mixture is then filtered by suction, and the precipitate is washed with concentrated hydrochloric acid followed by alcohol. The resulting dry stannous chloride salt of diaminoacetone weighs 80-87 g., which corresponds to an 80-85% yield. 

This salt is converted to the dihydrochloride by solution in 1.8 1. of water and saturation with hydrogen sulfide under slightly greater than atmospheric pressure. The precipitated tin sulfide is filtered off, 

The (+)-3-methoxy-N-methyl-morphinan-tartrate melts with 1 mol of water at 195°-196°C 

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The dihydrochloride is a white crystalline powder, m.p. about 225 C (decomp.). Used as an antiseptic and skin sterilizing agent, and as a bacteriostat in some pharmaceutical formulations. 

Basic, forms a stable water-soluble dihydrochloride. Diazotization gives brown azodyes (Bismarck brown) owing to the coupling of the partially diazotized base with the excess of diamine. Is also used as an end component of many azo-dyes, readily coupling with one or two molecules of diazo compound. 

Make a thin paste of 21 5 g. of finely-powdered o-tolidine (a commercial product) with 300 ml. of water in a 1-litre beaker, add 25 g. (21 ml.) of concentrated hydrochloric acid, and warm until dissolved. Cool the solution to 10° with ice, stir mechanically, and add a further 25 g. (21 ml.) of concentrated hydrochloric acid (1) partial separation of o tolidine dihydrochloride will occur. Add a solution of 15 g, of sodium nitrite in 30 ml. of water as rapidly as possible, but keep the temperature below 15° a slight excess of nitrous acid is not harmful in this preparation. Add the clear, orange tetrazonium solution to 175 ml. of 30 per cent, hypophosphorous acid (2), and allow the mixture to stand, loosely stoppered, at room temperature for 16-18 hours. Transfer to a separatory funnel, and remove the upper red oily layer. Extract the aqueous layer with 50 ml, of benzene. Dry the combined upper layer and benzene extract with anhydrous magnesium sulphate, and remove the benzene by distillation (compare Fig. II, 13, 4) from a Widmer or similar flask (Figs. II, 24, 3-5) heat in an oil bath to 150° to ensure the removal of the last traces of benzene. Distil the residue at ca. 3 mm. pressure and a temperature of 155°. Collect the 3 3 -dimethyldiphenyl as a pale yellow liquid at 114-115°/3 mm. raise the bath temperature to about 170° when the temperature of the thermometer in the flask commences to fall. The yield is 14 g. 

If the hydrochloric acid is added all at once instead of in two portions as detailed, a solid will be obtained consisting of o-tolidine coated with its dihydrochloride, and the diazotisation will proceed slowly. 

The crude o-phenylenediamine may be converted into the dihydrocliloride and the salt purified in the following manner. Dissolve it in 60 ml. of concentrated hydrochloric acid and 40 ml. of water containing 2 g. of stannous chloride, and treat the hot solution with 2-3 g. of decolourising carbon. Filter, add 100 ml. of concentrated hydrochloric acid to the hot colourless filtrate, and cool in a freezing mixture of ice and salt. Collect the colourless crystals of the dihydrochloride on a Buchner or sintered glass funnel, wash with a small volume of concentrated hydrochloric acid, and dry in a vacuum desiccator over sodium hydroxide. The yield is 61 g. 

Aza-8-germaspiro-[4,5]-decane-2-propanamine-8,8-diethyl-N,N-dimethyl dihydrochloride... 

Meclizine Hydrochloride. Pipera2ine Antivert, and Bonine are trade names for mech2ine dihydrochloride monohydrate [31884-77-2] (20). It is a white or slightly yellowish crystalline powder with a slight odor, no taste, and a melting point of 217—224°C. The hydrochloride is practically insoluble in water and ether. It is freely soluble in chloroform, pyridine, methylacetamide, and mild acid alcohol—water mixtures, and is slightly soluble in dilute acids or alcohol. See Reference 16 for synthesis. 

Pyrrohdines also can be obtained by reaction of 1,4-dihydroxyaLkanes with amines in the presence of dehydrating agents at elevated temperatures or by reaction of primary amines with 1,4-dihaloaLkanes. The dry distillation of 1,4-butanediamine dihydrochloride also generates pyrrohdine. Pyrroles can also be catalyticahy hydrogenated to pyrrohdines. 

Anthrahydroquinones have been patented in Japan as bird repeUents (73), and anthraquinone [84-65-1] (qv) is used widely in Europe as a spray to protect growing crops and as a wood dressing. The synthetic pyrethroid deltamethrin [52918-63-5] (27) was evaluated (74), as were other materials, including bendiocarb (20) (75) and 20,25-dia2ocholesterol dihydrochloride [1249-84-9] (Omitrol) (28), a steroid that inhibits embryo development when adsorbed or ingested as a seed treatment of bait com (55,76). 

Nitrite can be deterrnined by reaction with sulfanilamide to form the diazo compound, which couples with /V-(1-naphthyl)ethylenediamine dihydrochloride to form an intensely colored red azo dye. Nitrate can be deterrnined in a similar manner after reduction to nitrite. Suitable reducing agents are cadmium filings or hydrazine. This method is useful at a nitrogen concentration of 10 -lO " M. 

Quinacrine. Quinacrine (7), C23H2QCIN2O, is an acridine derivative. It is used in the form of the dihydrochloride dihydrate,... 

Hydrogen chloride gives a dihydrochloride. Chloroformamidine hydrochloride [29671-92-9] is a convenient anhydrous form of cyanamide that is easily handled and stored (16). 

V-Alkylpipera ines and PIP can react with nitrosating agents such as nitrogen oxides, nitrites or nitrous acid to form nitrosamine derivatives (61,62). Piper a2ine dihydrochloride [142-64-3] reacts with aqueous sodium nitrite and HCl to give the dinitrosamine that melts at 156—158°C (61). 

N — N — — Imidazole 4,5-di-t-butylimidazole histamine dihydrochloride 2-thio-hydantoin... 

Pterin, 6,7,7-trimethyl-7,8-dihydro-bacteriostatic activity, 3, 325 Pterin, 5,6,7-trimethyl-5,6,7,8-tetrahydro-dihydrochloride monohydrate X-ray analysis, 3, 281 Pterin-6-carbaldehyde, JV -acetyl-synthesis, 3, 312... 

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