Abstract: Described are granules composed at least of a substantial amount of ibuprofen, at least one pharmaceutically-acceptable super disintegrant, and at least one pharmaceutically-acceptable binder different from the super disintegrant(s), the super disintegrant(s) being substantially uniformly dispersed throughout the granules. The methods for preparing such granules are described. The granules are useful in forming solid dosage forms such as filled capsules or compressed solid dosage forms.

Abstract: Concentrated pourable potassium ibuprofen liquid compositions, and preparation and uses thereof are described. They are composed of (i) at least 60 wt % of potassium ibuprofen in dissolved form; (ii) water; (iii) one or more polyethylene glycols, (iv) optionally up to 5 wt % of at least one C2-3 alkanol; and (v) optionally, ibuprofen in free acid form. The weight ratio of (ii):(iii) is at least 0.9:1. Compositions containing as much as 85.2 wt % of potassium ibuprofen in dissolved form have been successfully made. The highest level of potassium ibuprofen in dissolved form achieved in experiments reported in the presently-known prior art is but 24.2 wt %. The present compositions are suitable for use in the preparation of pharmaceutical products and various pharmaceutical dosage forms such as liquid-filled soft gelatin capsules, syrups, elixirs, suspensions; solid dosage forms such as tablets or caplets; and topically-applied products. such as lotions, creams or ointments.

Abstract: Gaseous anhydrous hydrogen chloride is introduced into an aqueous solution of zinc chloride under conditions effective to produce a more efficient Lucas reagent than a Lucas reagent made by mixing solid, anhydrous zinc chloride with 38% hydrochloric acid. For example, the reaction rate of such Lucas reagent with levo-menthol is much faster and requires a much shorter reaction period than Lucas reagent formed in the conventional manner from anhydrous, solid zinc chloride and concentrated (38%) hydrochloric acid. Also, the conversion to levo-menthyl chloride was higher when using Lucas reagent formed using gaseous anhydrous hydrogen chloride and aqueous zinc chloride solution. Also, Lucas reagent made in this manner is highly amenable to recycling, and requires only addition thereto of hydrogen chloride to replenish the catalyst for an ensuing run.

Abstract: Bridged metallocene compounds are produced by a process of promising commercial utility for plant-sized operations. One of the key steps of the process involves converting a deprotonated silicon-, germanium- or tin-containing ligand into the metallocene. Preferably, and in accordance with an embodiment of the invention, this is accomplished to great advantage by adding a diamine adduct of a Group IV, V, or VI metal tetrahalide to a solution or slurry formed from a deprotonated silicon-, germanium- or tin-containing ligand and an organic liquid medium so as to form a metallocene. The overall process of the invention involves the direct conversion of benzoindanones to benzoindanols which, without isolation, are converted to benzoindenes. Thereupon the benzoindenes are bridged by deprotonating the benzoindenes with a strong base such as butyllithium and reacting the resultant deprotonated product with a suitable silicon-, germanium- or tin-containing bridging reactant such as dichlorodimethylsilane.

Abstract: N-?4-(Cyanoethylthiomethyl)-2-thiazolyl!guanidine, is prepared by (a) mixing 1,3-dihaloacetone and 2-imino-4-thiobiuret in a suitable polar organic solvent at initial temperatures of about -10.degree. to about 25.degree. C., and agitating the mixture at about -10.degree. to about 60.degree. C. for at least about 1 hour; (b) heating the resultant mixture at about 40.degree. to about 60.degree. C. for at least about 0.5 hour; (c) mixing with the mixture from (b), thiourea and then water at about 40.degree. to about 60.degree. C. for a period of at least about 1 hour; (d) removing liquid polar solvent from the mixture of (c); and (e) mixing with the mixture from (d), 3-halopropionitrile and water-soluble alcohol, ether, or ether-alcohol, followed by aqueous alkali metal hydroxide while maintaining the temperature at below about 20.degree. C., to form N-?4-(cyanoethylthiomethyl)-2-thiazolyl!guanidine.

Abstract: N-?4-(cyanoethylthiomethyl)-2-thiazolyl!guanidine--a key intermediate for preparing the pharmaceutical, famotidine--is produced by mixing in a liquid medium formed from a chemically indifferent organic solvent and water, and under an inert atmosphere, (i) a 2-guanidino-4-halomethylthiazole or a hydrohalide complex thereof, (ii) an S-(2-cyanoethyl)isothiourea or a hydrohalide complex thereof, and (iii) a strong alkali metal base. In lieu of (ii), an alkali metal salt of 2-cyanoethyl-1-thiol can be used, and in such case use of (iii) is optional, but preferable.

Abstract: Gaseous anhydrous hydrogen chloride is introduced into an aqueous solution of zinc chloride under conditions effective to produce a more efficient Lucas reagent than a Lucas reagent made by mixing solid, anhydrous zinc chloride with 38% hydrochloric acid. For example, the reaction rate of such Lucas reagent with levo-menthol is much faster and requires a much shorter reaction period than Lucas reagent formed in the conventional manner from anhydrous, solid zinc chloride and concentrated (38%) hydrochloric acid. Also, the conversion to levo-menthyl chloride was higher when using Lucas reagent formed using gaseous anhydrous hydrogen chloride and aqueous zinc chloride solution. Also, Lucas reagent made in this manner is highly amenable to recycling, and requires only addition thereto of hydrogen chloride to replenish the catalyst for an ensuing run.

Abstract: N-?4-(cyanoethylthiomethyl)-2-thiazolyl!guanidine--a key intermediate for preparing the pharmaceutical, famotidine--is produced by mixing in a liquid medium formed from a chemically indifferent organic solvent and water, and under an inert atmosphere, (i) a 2-guanidino-4-halomethylthiazole or a hydrohalide complex thereof, (ii) an S-(2-cyanoethyl)isothiourea or a hydrohalide complex thereof, and (iii) a strong alkali metal base. In lieu of (ii), an alkali metal salt of 2-cyanoethyl-1-thiol can be used, and in such case use of (iii) is optional, but preferable.

Abstract: Bridged metallocene compounds are produced by a process of promising commercial utility for plant-sized operations. The overall process involves the direct conversion of benzoindanones to benzoindanols which, without isolation, are converted to benzoindenes. Thereupon the benzoindenes are bridged by deprotonating the benzoindenes with a strong base such as butyllithium and reacting the resultant deprotonated product with a suitable silicon-, germanium- or tin-containing bridging reactant such as dichlorodimethylsilane. The resultant bridged product is deprotonated with a strong base such as butyllithium and reacted with a suitable Group IV, V, or VI metal-containing reactant such as ZrCl.sub.4 to provide a silicon-, germanium- or tin-bridged Group IV, V, or VI metal complex, such as a dihydrocarbylsilyl-bridged zirconocene complex.

Abstract: By reacting certain partially sterically-hindered chloro-substituted cycloalkanes with sodium and/or potassium diarylphosphides in an ether reaction medium, not only are useful cycloalkyldiarylphosphines produced, but in addition the chloro-substituted cycloalkane does not undergo any appreciable reaction with the coproduced aryl sodium and/or aryl potassium as it is formed. Moreover, the process makes it possible to avoid or at least to greatly reduce interaction with or cleavage of cyclic ether reaction media such as tetrahydrofuran. Thus the process makes possible improvements both in yield and quality of the cycloalkyldiarylphosphite product. A two-stage process conducted in an ether reaction medium is also described. In the first stage the sodium and/or potassium diarylphosphine reactant is produced by reaction between sodium and/or potassium and triarylphosphine.

Abstract: Partially sterically-hindered cycloalkyl chlorides are reacted with lithium diarylphosphides in inert liquid hydrocarbon reaction media to form cycloalkyldiarylphosphines. Aryl lithium is coproduced. The process makes it possible to avoid, or at least substantially eliminate, the interaction with or cleavage of cyclic ether reaction media such as tetrahydrofuran, previously the solvent of choice for conducting this type of reaction. Also during the conduct of the present process the chloro-substituted cycloalkane does not undergo any appreciable reaction with the coproduced aryl lithium as it is formed. Thus improvements both in yield and quality of the cycloalkyldiarylphosphine product are made possible. A comprehensive three-step process for converting triarylphosphine to cycloalkyldiarylphosphine is also described.

Abstract: Lithium aluminum hydride reacts with a tertiary amine to produce an amine alane and Li.sub.3 AlH.sub.6. Lithium values are recycled by reacting Li.sub.3 AlH.sub.6 with aluminum and hydrogen to produce LiAlH.sub.4. Since no metal halide by-product is produced in the first step, it has an advantage over other routes. The amine alane can react with SiF.sub.4 to produce silane and AlF.sub.3.

Abstract: Silane and monoalkylsilanes can be alkylated using an alkali metal aluminate, MAlR.sub.4, wherein M is Li, Na, or K and each R is a straight chain, alkyl radical solely composed of carbon and hydrogen containing from about 4 to about 18 carbon atoms. The aluminate can be used as a reactant, optionally in the presence of a straight chain alpha-olefin corresponding to the alkyl group in the aluminate. Alternatively, the aluminate can be used as a catalyst for the reaction of the olefin and the silane reactant, in which case from about 5 to about 10 mole percent of the aluminate (based on the silane reactant) is employed. The catalytic reaction is promoted by a smaller amount of a lithium salt such as lithium chloride. Both embodiments are conducted at somewhat elevated temperatures, approximately 160.degree.-210.degree. C., and at autogenous pressures, using reaction times of 8-20 hours.The products are useful as functional fluids or as intermediates.