Methylene chloride, impurities

The organic layer is separated, evaporated on a steam bath, and the dark semicrystalline residue is distilled with steam to remove biphenyl. The contents of the steam-distillation flask are then extracted with ether (Note 3), and the ethereal layer is separated, dried over magnesium sulfate, and percolated through a short column of chromatographic alumina (Notes 4 and 5). Evaporation of the ethereal solution gives crude triphenylene which is sublimed at 175-180° and 0.1 mm. pressure. After rejection of an initial sublimate of impure biphenyl, the sublimed material forms nearly colorless crystals, m.p. 186-194° (Note 6). Yield 8-9 g. (53-59%). It may be further purified by recrystallization from a mixture of methylene chloride and pentane yielding colorless crystals, m.p. 199° (Note 7). 

Ninety-eight grams of 6-chloro-2-chloromethyl-4-phenylquinazoline 3-oxide hydrochloride were introduced into 600 cc of ice cold 25% methanolic methylamine. The mixture was initially cooled to about 30°C and then stirred at room temperature. After 15 hours the reaction product which precipitated was filtered off. The mother liquor was concentrated in vacuo to dryness. The residue was dissolved in methylene chloride, washed with water and dried with sodium sulfate. The methylene chloride solution was concentrated in vacuo and the crystalline residue was boiled with a small amount of acetone to dissolve the more soluble impurities. The mixture was then cooled at 5°C for 10 hours and filtered. The crystalline product, 7-chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine 4-oxide, was recrystallized from ethanol forming light yellow plates, MP 236° to 236.5°C. 

After 30 minutes the solid sulfinic acid is separated on a fritted-glass filter. The sulfinic acid is dissolved from the filter by a mixture of 750 ml. of ether and 750 ml, of methylene chloride. The solution is dried over calcium chloride and evaporated to dryness under reduced pressure (bath temperature 25°) (Note 5). The residue is suspended in 50 ml. of water, and small portions of dilute ammonia are added to the well-stirred suspension until it has a pH of 9 (Note 6). Insoluble impurities are separated by filtration, and 2-nitrobenzenesulfinic acid is precipitated from the filtrate by adding 5-ml. portions of 6N hydrochloric acid with cooling the sulfinic acid precipitated by each portion of acid is separately collected on a Buchner funnel (Note 7). The acid, a pale yellow solid, is dried on a clay plate in a vacuum desiccator over potassium hydroxide pellets, m.p. 120-125° (dec.), weight 9.4-14.9 g. (50-80%). If the 2-nitrobenzenesulfinic acid is to be used for the hydrogenation of the next step high purity is required, and it is generally advisable to reprecipitate the acid once more in the same way (Note 8). 

The last part of the procedure can be used to purify nitronium tetrafluoroborate that has picked up water on standing. The impure salt is washed twice with nitromethane, twice with methylene chloride, and is dried under reduced pressure. 

Further rinsing with methylene chloride yielded trace quantities of additional product, which was less pure by HPLC analysis. The main impurity was 2 (see Discussion) produced by cleavage of the t-butyl ester by the Amberlyst 15 resin. 

The possibility exists that the acid used in hydrolysis could catalyze the hydrolysis of the succinic ester group in the middle of the telechelomer itself. Even though NMR ( H and C) cannot easily eliminate this possibility, we have evidence that such a hydrolysis did not take place. For instance, hydrolysis should result in the formation of poly(pivalolactone) which is insoluble both in methylene chloride and water, but no insolubles were evident. Also, the Gel Permeation Chromatograms do not show impurities in the product. 

Rapid-acting dermally hazardous cytotoxin that inhibits protein synthesis and affects clotting factors in the blood. It is capable of producing incapacitating or lethal effects. T2 is obtained from various molds and fungi (Fusarium sp.). It is a colorless crystalline solid of white powder that melts at 304°F. Impure samples may be a colorless to slightly yellow oil. It is slightly soluble in water, but soluble in ethyl acetate, acetone, ethanol, chloroform, methylene chloride, diethyl ether, and dimethyl sulfoxide (DMSO). It is heat stable and can be stored at room temperature for years. 

Common HPLC solvents with adequate purity are commercially available. Halogenated solvents may contain traces of acidic impurities that can react with stainless steel components of the HPLC system. Mixtures of halogenated solvents with water should not be stored for long periods, as they are likely to decompose. Mixtures of halogenated solvents with various ethers, e.g., diethyl ether, react to form products that are particularly corrosive to stainless steel. Halogenated solvents such as methylene chloride react with other organic solvents such as acetonitrile and, on standing, form crystalline products. 

Halomethanes, including methylene chloride, chloroform, and carbon tetrachloride (di-, tri-, and tetrachloromethane, respectively), are used mainly as raw materials and solvents in approximately 28 pesticide processes. Bromomethanes can be expected in at least five pesticides as raw materials, byproducts, or impurities and in the case of methyl bromide, can function as a fumigant. 

This material is sufficiently pure for use in the next step. Analysis by C NMR indicates that 2-4% of an unknown impurity Is present. Recrystallization from hexane-methylene chloride gives pure product melting at 37-38°C... 

Tetrahydrofuran (THF, UV grade) was used as the mobile phase throughout this work since the extent of fractionation could be demonstrated by direct analysis of the preparative fractions without the need for concentration. When samples are to be recovered by removal of solvent, other mobile phases (methylene chloride, etc.) may be preferred to avoid concentrating solvent impurities which are formed in THF on exposure to air unless additional precautions are taken. 

OSL Impurities. It was also of interest to determine the impurities removed from crude OSL by reslurry in aqueous sodium bicarbonate, which was done to improve its usefulness in phenolic resins (Cook, P. M., Eastman Kodak at Kingsport, TN, personal communications, 1987). Extraction and acetylation procedures, involving methylene chloride, acetic anhydride pyridine... 

The assay was carried out using a Varian gas chromatograph (model 5000 LC) under the following experimental condition. The oven injector and flame ionization detector temperatures were 125°C and 225°C respectively. A Porapak column was used, the eluent was N2 at a flow rate of 30 ml/min and the injected volume 2 pi. Various concentrations of purified methylene chloride in purified methanol were injected (both solvents were distilled to discard any impurity which might interfere with the sensitive assay). Calibration curves were linear in the range 50-500 ppm (the limit of detection was 10 ppm). Methylene chloride detection in the microspheres was performed by dissolving various amounts (20-200 mg) of microspheres in 220 ml of purified methanol prior to the injection. 

HUMIC Acid. Humic acid did not contribute detectable impurities to the eluates of blank parfait columns. This result was apparently due to the insolubility of humate in the organic solvents used to elute the Teflon and ion-exchange beds and the inability of the humate to volatilize in the GC. Humic acid did, however, distribute itself throughout the parfait column, as indicated by the observation of color entering the column effluent, F7. When 16 mg of humate in 8 L of synthetic hard water was passed through a parfait column having the Teflon bed divided into three sequential 50-mL beds, 8.9 , 5.0 , and 2.9 of the total humate were found in the aqueous phases that separated upon elution of these beds, as indicated by absorbance at 200 nm. The column effluent from this experiment contained 5.1 of the humate applied. The majority of the humate applied was found as color adsorbed to PTFE, and it did not elute into methylene chloride. Conditions to elute it from PTFE were not explored. 

DNPH is often susceptible to formaldehyde or acetone contamination. It should, therefore, be crystallized with acetonitrile to remove any impurities. Repeated crystallization may further be performed to achieve the desired level of purity for DNPH. A 100-mL aliquot of aqueous sample is buffered with a citrate buffer and pH adjusted to 3 0.1 with HC1 or NaOH. The acidified sample is then treated with DNPH reagent and heated at 40°C for an hour under gentle swirling. The DNPH derivatives of aldehydes and ketones formed according to the above reaction are extracted with methylene chloride using liquid-liquid extraction. The extract is then solvent exchanged to acetonitrile for HPLC determination. 

The United States Pharmacopeia (USP) test (467) describes three different approaches to measuring organic volatile impurities in pharmaceuticals. Method I uses a wide-bore coated open tubular column (G-27, 5% phenyl-95 % methylpolysiloxane) with a silica guard column deactivated with phe-nylmethyl siloxane and a flame-ionization detector. The samples are dissolved in water and about 1 p is injected. Limits are set for benzene, chloroform, 1,4-dioxane, methylene chloride, and trichloroethylene. Methods V and VI are nearly identical to method I except for varying the chromatographic conditions. For the measurement of methylene chloride in coated tablets, the headspace techniques described above are recommended. 

As mentioned, the spectrum and amount of impurities formed during oxychlorination is much larger compared with direct chlorination. Some key impurities are listed below 1,1,2-trichloroethane (TCE), chloral (CCl3-CHO), trichloroethylene (TRI), 1,1- and 1,2-dichloroethylenes, ethyl chloride, chloro-methanes (methyl-chloride, methylen-chloride, chloroform), as well as polychlorinated high-boiling components. In particular, chloral needs to be removed immediately after reaction by washing because of its tendency to polymerization. 

Note If the toluenesulfonamide content of the sample is greater than about 500 mg/kg, the impurity may crystallize out of the methylene chloride concentrate (see Test Preparation). Although this level of impurity exceeds that permitted by the specification, the analysis may be completed by diluting the concentrate with methylene chloride containing 250 p,g of w-tricosanc per milliliter, and by applying appropriate dilution factors in the calculation. Care must be taken to redissolve completely any crystalline toluenesulfonamide to give a homogeneous solution. 

To determine perchloroethylene and higher-boiling impurities, substitute methylene chloride (free of interfering impurities) for perchloroethylene in the extraction step. For higherboiling impurities such as monochlorobenzene and the three dichlorobenzenes, use a 2.74-m x 2.1-mm (id) stainless-steel column packed with 10% carbowax 20M/2% KOH on 80- to 100-mesh chromasorb W (acid washed), set at 150° and with a nitrogen flow of 35 mL/min. 

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