Methylene-amine acetonitrile chloride

An elecrophilic Br+ or I+ can be successfully transferred to hydroquinidine (13) and two of its commercially available derivatives (4-chlorobenzoate and 9-phenanthryl ether hydroquinidines) simply by mixing two equivalents of the hydroquinidine with one equivalent of sym(co d ne)2-X+ perchlorate in methylene chloride or acetonitrile. H NMR studies (31) showed that the iodonium ion was associated with the nitrogen at the quinuclidine portion of the hydroquinidine instead of the aromatic nitrogen and also that all of the sym-collidines were removed from the X+ since only free collidine and no collidine-I+ peaks were observed. The (hydroquinidine)2-halonium ion is stable in solution for more than 30 minutes at room temperature these ions (and their parent amines) are more soluble in methylene chloride than in acetonitrile, and having R group other than hydrogen also improves the solubility. 

N-NeoDentyl)-4-DihexylaminoDvrldinium Bromide (3h) The neopentyl salt was prepared in a similar manner from neopentyl mesylate, but reaction was carried out neat at 130 for 72 hr. Higher temperatures cannot be used, due to decomposition of neopentyl mesylate. The crude product was dissolved in water, basifled to neutralize any pyridinium salt, and was washed with petroleum ether to remove amine and unreacted neopentyl mesylate. The aqueous phase was acidified with HBr, and extracted with methylene chloride, to afford crude salt. Recrystallization from 20 1 ethyl acetate/acetonitrile affords the product (mp = 169-170 ). 

While nitramines are formed from the reaction of secondary amines with nitronium salts the success of the reaction depends on the basicity of the amine (Equation 5.11). Thus, amines of low to moderate basicity are A-nitrated in good yields. The nitration of more basic amines is slow and the nitrosamine is often observed as a significant by-product, a consequence of the partial reduction of the nitronium salt to the nitrosonium salt during the reaction. Increased reaction temperature is also found to increase the amount of nitrosamine formed. The amine substrate is usually used in excess to compensate for the release of the strong mineral acid formed during the reactions. Both nitronium tetrafluoroborate and the more soluble hexafluorophosphate are commonly used for A-nitrations. Solvents like acetonitrile, methylene chloride, nitromethane, dioxane, sulfolane, ethyl acetate and esters of phosphoric acid are commonly used. 

The efficient At-nitration of secondary amines has been achieved by transfer nitration with 4-chloro-5-methoxy-2-nitropyridazin-3-one, a reagent prepared from the nitration of the parent 4-chloro-5-methoxypyridazin-3-one with copper nitrate trihydrate in acetic anhydride. Reactions have been conducted in methylene chloride, ethyl acetate, acetonitrile and diethyl ether where yields of secondary nitramine are generally high. Homopiperazine is selectively nitrated to At-nitrohomopiperazine or At, At -dinitrohomopiperazine depending on the reaction stoichiometry. At-Nitration of primary amines or aromatic secondary amines is not achievable with this reagent. 

A solution of dinitrogen pentoxide in methylene chloride-acetonitrile also yields secondary nitramines from symmetrical methylenediamines. When the substiment is aliphatic or heterocyclic the nitrolysis occurs specifically at the aminal methylene and yields of secondary nitramine between 25 % and 54 % are reported. 

The mobile phases used in reversed-phase chromatography are based on a polar solvent, typically water, to which a less polar solvent such as acetonitrile or methanol is added. Solvent selectivity is controlled by the nature of the added solvent in the same way as was described for normal-phase chromatography solvents with large dipole moments, such as methylene chloride and 1,2-dichloroethane, interact preferentially with solutes that have large dipole moments, such as nitro- compounds, nitriles, amines, and sulfoxides. Solvents that are good proton donors, such as chloroform, m-cresol, and water, interact preferentially with basic solutes such as amines... 

Reaction of a primary aliphatic amine, n-butylamine, with nitronium tetrafluoroborate in methylene chloride or acetonitrile produced not n-butylnitramine, but n-butyl nitrate in about 20% yield. However, treating an electronegatively substituted primary aromatic amine, picramide, with nitronium tetrafluoroborate did give the primary nitramine, N,2,4,6-tetra-nitroaniline, in 85% yield. Olah (16) had reported previously that aniline was oxidized vigorously by nitronium salts. 

Aryl halides are frequently prepared from the corresponding aryldiazonium salts by diazotation procedures. However, diazonium salts can be subjected directly to very mild Heck arylation conditions, which deliver coupled products (entry 19). Preferably, the reaction is executed in nonaqueous solvents such as acetonitrile, acetone, or methylene chloride with sodium acetate as base and with palladiumbis(dibenzylideneacetone) as catalyst. Alternatively, a combination of the amine and f-butyl nitrite, in a mixture of acetic acid and monochloroacetic acid, can provide the desired product directly, which makes the isolation of a diazonium salt unnecessary (entry 20). " It is also possible to use aromatic acid anhydrides as oxidative addition precursors (entry 21). Clearly, anhydrides are very interesting starting materials for a number of Heck reactions due to price and absence of halide salt formation. 

As an alternative to the potassium salt, tertiary amines and tetra-alkylammonium salts have been used instead. The acids, e.g. the dried residue from a serum extraction, are treated with an acetonitrile solution of pentafluorobenzyl chloride and di-isopropylethylamine, in a 3 1 molar ratio, at 40 °C for 5 minutes. The reaction mixture is blown dry with nitrogen if necessary the esterification may be repeated (96). lndole-3-acetic acid was similarly esterified, but using acetone as solvent and N-ethylpiperidine as the cation and reaction for 45 minutes at 60 °C [97). Tetrabutylammonium hydrogen sulphate (0.1 mmol) was converted to the hydroxide with sodium hydroxide (0.2 mmol) and added to the dried acids in a serum extract with 1 ml of methylene chloride and 20 pi of pentafluorobenzyl bromide. The mixture was vigorously shaken for 30 minutes and blown down to dryness with nitrogen, and the esters were extracted into hexane for HPLC [98,99). 

Ethyl phenylalanate added to a soln. of cyclopropanone in methylene chloride stirred 45 min. at -78° and 0.5 hr. at 0°, the soln. containing the resulting carbinol-amine treated with NaHCO followed by t r -butyl hypochlorite at -15 to -10° in the dark, stirred 40 min., dil. with dry acetonitrile, treated with a 3-fold excess of Ag-nitrate, allowed to warm to room temp., and the product isolated after 1.5 hrs. stirring -> l-(a-carbethoxy-j -phenyl)ethylazetidin-2-one. Y 70%. F. e. s. H. H. Wasserman and E. Glazer, J. Org. Chem. 40, 1505 (1975). 

The nonsteric interactions in ipc depend on the chemical structure of the analyte, and also on nature of stationary and mobile phases. In normal- or reversed-phase hplc, neutral solutes are separated on the basis of their polarity. In the former case, polar stationary phases are employed (eg, bare sihca with polar silanol groups) and less polar mobile phases based on nonpolar hydrocarbons are used for elution of the analytes. Solvent selectivity is controlled by adding a small amoimt of a more polar solvent, such as 2-propanol or acetonitrile or other additives with large dipole moments (methylene chloride and 1,2-dichloroethane), proton donors (chloroform, ethyl acetate, and water), or proton acceptors (alcohols, ethers, and amines). Correspondingly, the more polar the solute, the greater is its retention on the column, yet increasing the polarity of the mobile phase results in decreased solute retention. 

PVOCCl samples were obtained by pol)mierization of pure VOCCl (acquired from the SNPE, purity > 99%) in methylene chloride at 35 C using dicyclohexyl peroxydicarbonate as initiator 8-11, Amines, alcohols, phenols, 2-oxazolidone and KCN were commercial products used without special purification. Amines were redistilled under nitrogen just before use. Traces of methanol were removed from methylene chloride and THF was distilled on sodium cuttings under nitrogen before use. Acetonitrile (ACN) as well as the phase-transfer-cata-lysts SO/HNBu (TBAH) and dicyclohexyl-18 crown-6 (DCHE) were used without... 

Typically, DCC (1.1 equiv) is added to a concentrated solution (0.1-1.0 M) of the carboxylic acid (1.0 equiv), amine (1.0 equiv), and catalyst (when used) in methylene chloride or acetonitrile at 0 °C. The hydrated DCC adduct, dicyclohexylurea (DCU), quickly precipitates and the reaction is generally complete within 1 h at rt. The solvents THF and DMF can be used, but are reported to reduce reaction rates and encourage the formation of the A -acylurea side product, as well as increasing racemization in chiral carboxylic acids.If the amine is initially present as the salt (i.e. amine hydrochloride), it may be neutralized by adding 1 equiv of Diisopropylethylamine prior to adding DCC however, the addition of tertiary amines (particularly Triethylamine) can facilitate A -acylurea formation and racemization. Racemization occurs via the formation of an oxazalone intermediate. The addition of coupling agents (acylation catalysts) such as 1-Hydroxybenzotriazole (HOBt), l-hydroxy-7-azabenzotriazole... 

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