Free bases preparation methods

Solid Phase MicroExtraction (SPME) is a solvent-free sample preparation method based on the adsorption of analytes directly from an aqueous sample onto a coated fused-silica fiber. Headspace SPME was used in combination with gas chromatography-mass spectrometry/ selective ion monitoring (GC/MS-SIM) to analyze for TCA in wine. 

Solid-phase microextraction (SPME) was introduced in the early 1990s by Arthur and Pawliszyn. SPME is a simple solvent-free sample preparation method for GC and LC. The extraction is based on the partitioning of the analyte between the organic phase on the fused silica fiber and the matrix. Many factors such as pH, temperature, salt concentration, and stirring affect the equilibrium constant and the equihbration time. Fiber lifetime is a significant issue. SPME fiber is quite sensitive to complex matrix such as... 

Additional advantages are offered by extending the applicability of the MALDI methods to insoluble polymers [65] and saturated polyolefins [66]. One of the key factors that influence the success and the quality of MALDI mass spec-trometric analysis is the sample preparation. Thus, prerequisites for traditional sample preparation method require soluble analytes and matrices and the compatibility of the solvents for both matrix and analyte systems, subsequent solvent removal, and the homogeneity of the crystallized analyte/matrix mixture on the surface of the MALDI sample holder [67-71]. These factors can introduce severe mass discrimination effects. The advantages of solvent-free preparation in comparison to conventional solvent-based MALDI-MS were recently reported [65, 72]. The MALDI mass spectra obtained by the solvent-free sample preparation method were compared by Trimpin et al. [72] with mass spectra obtained by conventional solvent-based MALDI-MS and by laser desorption (LD)-MS under identical experimental conditions, stressing the capability of solvent-free MALDI-MS to characterize insoluble samples. 

Usually metal-free phthalocyanine (PcH2) can be prepared from phthalonitrile with or without a solvent. Hydrogen-donor solvents such as pentan-l-ol and 2-(dimethylamino)ethanol are most often used for the preparation.113,127 128 To increase the yield of the product, some basic catalyst can be added (e.g., DBU, anhyd NH3). When lithium or sodium alkoxides are used as a base the reaction leads to the respective alkali-metal phthalocyanine, which can easily be converted into the free base by treatment with acid and water.129 The solvent-free preparation is carried out in a melt of the phthalonitrile and the reductive agent hydroquinone at ca. 200 C.130 Besides these and various other conventional chemical synthetic methods, PcH2 can also be prepared electrochemically.79... 

Transformation of bromocriptine free base 2 into water soluble salt -mesylate, is the only way to obtain a suitable therapeutical form. Crystallization of mesylate using alcohol as a solvent in the presence of excess of strong acid, e.g. methanesulphonic acid can induce formation of 12 -0-alkyl-derivative 2. Until now this derivatisation of ergot molecule has been practically unknown. In continuation we developed the preparative method for obtaining these compounds, (using tetrafluoroboric acid as a catalyst) (ref. 20). 

Geiser et al. [50,51] illustrated the screening of different chiral stationary phases and the separation of highly polar amine hydrochlorides using EEL methanol/C02 mixtures and the columns, Chiralpak-AD-H, Chiralpak-AS. This method is advantageous because no acid or base additive was required to achieve base line separation of the racemates and conversion to free base form for enantiomer separation was not required. Preparative-scale separations of the amine-hydrochloride were accomplished using similar mobile phase conditions [51], Furthermore, this is believed to be the first chiral separation of highly polar solutes without the addition of acid or base additive to effect the separation. 

An alternative method for the preparation of the dihydrodiazepinium salt 5 involves the reaction of ethylenediamine dihydrochloride with ace-tylacetone [67JCS(C)2400]. Dihydrodiazepines have also been obtained from reactions between diketones and ethylenediamine (free base) in ethanol (71 Mil 78JIC577 78MI1). 

Radical attack on isoquinoline, as either free base or isoquinolinium cation, always occurs at position 1 and the method is not suitable for the preparation of benzo ring-substituted products. The same can be said of radical attack on the JV-oxides of quinoline and isoquinoline. 

Hydroxylamlne base has been prepared by the method of Lecher and Hofmann/ The free base can be stored in a tightly stoppered flask at -20°C for several days. The checkers found 1t expedient to prepare free hydroxylamine by a modification of the Lecher and Hofmann procedure in which a Schlenk tube under dry Ng was used to filter the NaCl precipitate and the NH20H base was crystallized from the filtrate at -30°C, then isolated by inverting the Schlenk apparatus and filtering the product (74% yield from the hydrochloride). 

This reaction can be employed to remove a primary amino group from an aromatic compound, especially. when the ordinary method of direct reduction of the diazonium compound by sodium stannite or alcohol is not applicable. Although in the application of this method the hydrazine can be prepared as the hydrochloride, and reduced in the same solution, yet it is better to isolate the free base and oxidise it separately, since in the oxidation of the hydrochloride there is a tendency for the hydrazine radical to be replaced by chlorine. 

Arylhydrazines may be prepared by reducing diazonium salts with excess warm sodium sulphite solution, followed by acidification with hydrochloric acid. The hydrochloride usually crystallises out on cooling and treatment of the latter with excess sodium hydroxide solution liberates the free base. The preparation of p-nitrophenylhydrazine by this method is illustrated in Expt 6.92. 

Rasmussen [540] applied on-column silylation to the quantitative determination of morphine. A 1-jul volume of a morphine solution in ethyl acetate (containing ca. 1 /ig of the drug) and 2 jul of TMSIM were injected with temperatures of the injection port and of the column of 275 and 250°C, respectively, using 3% of Dexsil 300 as the stationary phase. It was stated that in this arrangement no free bases could be detected, i.e., the conversion was complete and the method provided reproducible results (the coefficient of variation was 1.3%). It was recommended preferrably for the rapid checking of pharmaceutical preparations. 

---