Dichloro methylamine

Cyanoamidines such as (10) are converted into the more useful 2-formyl-A-norsteroids (11) by reduction with lithium in methylamine (buffered with ammonium acetate) followed by hydrolysis on hydrated alumina. This yields a mixture containing approximately 5 parts of the 2j5-aldehyde and 3 parts of the 2a-aldehyde (11). Both aldehydes are smoothly dehydrogenated by 2,3-dichloro-5,6-dicyanobenzoquinone in the presence of acid to the 2-formyl--A-iiorsteroids (12). ... 

Dichloro-s-triazine and its 6-alkyl analogs are as easily hydrolyzed by water as trichloro-s-triazine and, on suspension in aqueous ammonia (25°, 16 hr), the first is diaminated in good yield. 2,4-Bistrichloromethyl-6-methyl- and -6-phenyl-s-triazines (321) require a special procedure for mono-alkoxylation (0-20°, 16 hr, alcoholic triethylamine) disubstitution occurs at reflux temperature (8 hr). Aqueous triethylamine (100°, 3 hr) causes complete hydroxy-lation of 2,4,6-tris-trichloromethyl-s-triazine which can be mono-substituted with ammonia, methylamine, or phenoxide ion at 20°. 

This iron-ate complex 19 is also able to catalyze the reduction of 4-nitroanisole to 4-methoxyaniline or Ullmann-type biaryl couplings of bis(2-bromophenyl) methylamines 31 at room temperature. In contrast, the corresponding bis(2-chlor-ophenyl)methylamines proved to be unreactive under these conditions. A shift to the dianion-type electron transfer(ET)-reagent [Me4Fe]Li2 afforded the biaryl as well with the dichloro substrates at room temperature, while the dibromo substrates proved to be reactive even at —78°C under these reaction conditions. This effect is attributed to the more negative oxidation potential of dianion-type [Me4Fe]Li2. 

Typically, the resin is washed with a mixture of dichloro-methane and methanol (2 1 5 x 10 mL, shaking for 0.5 min each time), with a mixture of dichloromethane (9mL) and methylamine (1 mL, 30% solution in ethanol), with 1,2-dichlo-ropropane (10 mL) over night, with a mixture of dichloromethane (9 mL) and acetic acid (1 mL trityl resin-bound products should not be washed with diluted acetic acid), with a mixture of dichloromethane and methanol (2 1 3 x 10 mL, shaking for 0.5 min each time), and finally with dichloromethane (10 mL). Shorter washing protocols can lead to significant amounts of residual DBU in the final products. 

One of the early syntheses of meperidine (75) starts with the double alkylation of phenylacetonitrile with the bischloro-ethyl amine, 72. The highly lachrimatory nature of this material led to the development of an alternate synthesis for the intermediate piperidine (73). Alkylation of phenylacetonitrile with two moles of 2-chloroethylvinyl ether leads to the intermediate (69). This is then hydrolyzed without prior isolation to the diol, 70. Treatment with thionyl chloride affords the corresponding dichloro compound (71). This last is then used to effect a bis alkylation on methylamine, in effect forming the piperidine (73) by cyclization at the opposite end from the original scheme. Saponification to the acid (74) followed by esterification with ethanol affords the widely used analgesic meperidine (75) substitution of isopropanol for ethanol in the esterification affords properidine (76). ... 

This product was prepared by Blanksma [69] by the nitration of 2,4,6-trinitro-1,3,5-trimethylaminobenzene. The latter was obtained from 3,5-dichloro-(or di-bromo)-2,4,6,-trinitroanisole by the action of an alcoholic solution of methylamine. 

Tetranitro-N,N -Dimethyl-3,3 -di(methy lamino)-dipheiiyl, (02N)2CbH2(NH..CH3)-C6H2(NH.CH3)(N02)2 mw 392.28, N 21.43% yel powd, mp — explodes when heated above 360° turns reddish-bm when exposed to light was obtd when tecranitro-3,3 -dichloro-aiphenyl was heated with methylamine ale for 5 hrs at 100° (Ref 3)... 

Boron trifluoride and boron trifluoride-diethyl ether complex can be used as a source of fluoride ions in the presence of hypobromites and hypochlorites, e.g. methyl hypobromitc, tert-butyl hypobromite, methyl hypochlorite in carbon tetrachloride at 25 C. The addition of bromine monofluoride" and chlorine monofluoride" to various alkenes is accompanied by the formation of the corresponding alkoxybromides and alkoxychlorides which hinder the isolation of the halofluorinated products.57 jV-Bromo- and A -chloro-substiluted alkyl- and arylamines. -amides, and -imides, A -chloro-A,-methylamine, A -bromo-A -methylamine, A -chloro-A, /V-dimethylamine, A-bromo-A.A-dimethylamine, ACV-dichloro-A -methylamine, V,fV-dibromo-,V-mcthylaminc, A -bromosuccinimide, -V-chlorosuccinimide, Af-bromoacct-amide, A.A -dichlorourethane, can be used in the reaction instead of the hypohalites. The reactions with various alkenes conducted in dichloromethane at room temperature in the presence of boron trifluoride-diethyl ether complex produce bromofluoro and chlorofluoro addition products in 40-80 % yield. However, the reactions are complicated by the addition of A -halo-succinimides and Af.A-dichlorourcthane to the C = C bonds.58... 

Druey et have performed reactions of 4-methyl-3,6-dichloro-pyridazine with ammonia and other nucleophiles, but did not establish their structures. Later studies revealed that treatment of the mentioned pyridazine with anhydrous ammonia in methanol at 120° afforded a mixture of aminochloro-4-methylpyridazines in the ratio of about 1 10, the isomer 73a (X = NH2, R = Me) predominating. Also modified reaction conditions have led to a mixture of both isomers, where the isomer 73a was prevailing, and when di-methylamine has been used only isomer 73a (R=Me, X = NMe2) was isolated. From the reaction with hydrazine hydrate the isomer 74a (R=Me, X = NHNH2) is claimed to be the main product. 

DICHLOREN (GERMAN) p,p -DICHLORODIETHYL-N-METHYLAMINE DI(2-CHLOROETHYL)METHYL-AMINE 2,2 -DICHLORO-N-METHYLDIETHYLAMINE... 

The synthesis of unnatural (+)-mesembrine (387) through the asymmetric synthesis of methyl (i )-l-[(3,4-dimethoxy)phenyl]-4-oxocyclohex-2-enyl acetate (390) by cycloaddition of enantiomerically pure vinyl sulfoxide with dichloroketene has been performed 189) (Scheme 43). Vinyl sulfoxide 388 [prepared by conjugate addition of enantiopure acetylenic sulfoxide with (3,4-dimethoxy)phenylcopper] reacted with trichloroacetyl chloride in the presence of freshly prepared zinc-copper couple in THF at 0°C to produce a mixture of mono- and dichloro lactones 389. Reduction of 389 with zinc in acetic acid followed by cyclization and methylation afforded methyl IR-[(3,4-dimethoxy)phenyl]-4-oxocyclohex-2-enyl acetate (390), treatment of which with methylamine brought about amidation and concomitant intramolecular Michael addition to provide 2-oxo-mesembrine (391). Successively, 391 was transformed to (+)-mesembrine (387) in 79% yield (three steps ketalization of an oxo group, reduction of lactam, and deketali-zation)(/S9). 

An orientation of leaving group to azinone moiety suitable for activation or, at least, appreciable reactivity exists in various 3-pyridazinones. 6-Bromo- and 6-chloro-2-phenyl-3-pyridazinones react at 20° with methylamine. In 4,6,-dichloro-2-phenyl-3-pyridazin-one, ° inductive meta activation by the partly cationic ring-nitrogen... 

Dehydrohalogenation with rearrangement [1, 917-918, after Gardner and coworkers.36 ]. Dehydrochlorination of (2,2-dichloro-3,3-dimethylcyclopropyl)di-methylamine (7) with the reagent leads to the alkenynylamine (8) in 20-30% yield.36 The mechanism is not clear, but attempts to trap a cyclopropene intermediate failed. 

Dichloro-A, A -diethyl-l,3,5-triazin-6-amine (44 g, 0.2 mol) was dissolved in acetone (100 g) and distributed as finely as possible by pouring the solution into ice water (200 g). Methylamine (13 g, 0.42 mol) in H20 (40 mL) was then added, dropwise, at 10- 15°C and the whole mixture was stirred for 1 h at rt. The crude product was obtained in nearly quantitative yield (43 g) by filtration of the crystalline precipitate. Recrystallization from EtOH gave the title compound in the form of long white needles mp 144-146.5 °C. 

Norflurazone production is based on the condensation of 3-trifluormethyl-phenylhydrazine and mucochloric acid followed by cyclization with acetic anhydride to give 4,5-dichloro-2-(3-trifluormethylphenyl)pyridazin-3-one (54). Nucleophilic substitution of 54 with methylamine yields norflurazon [34]. 

According process A, l,l-dichloro-2-nitroethene (6) [10] is transformed into 1,1-bis(methylthio)-2-nitro-ethene (7) [11], which reacts in the first step with N-methylamine to give l-methylthio-l-(N-methyl)-amino-2-nitroethene (8), and in the second step with N-(6-chloro-pyrid-3-ylmethyl)-N-ethyl-amine (9b, CPM-NHEt) [12, 13] to yield 1. By process B, 6 is treated with (9b) to give 1-chloro-l-[N-(6-chloro-pyrid-3-ylmethyl)-N-ethyl]-amino-2-nitroethene (10) in situ, which reacts with N-methylamine to form 1 [14]. 

Thioridazine enantiomers were extracted from serum and separated on a phenyl-methylurea colunm (2=263nm) using a 45/45/10/0.0075 hexane/dichloro-methane/methanol/1 M methanolic ammonium acetate mobile phase [740]. Resolution vms good and peaks eluted in < 10 min. Analyte peaks were well removed from serum components and detection limits of 50ng/mL woe reported. Additionally, thioridazine and eight of its metabolites (e.g., thioridazine fV-oxide, northioridazine, and thioridazine 5-sulfate and disulfone) were baseline resolved in <12 min using a silica colunm (2 = 254 run) and an 8/1/1 iso-octane/methanol/dichloromethane (0.036% methylamine) mobile phase [741]. 

Poly [ (amino) phosphazenes] have been synthetised by the replacement of chlorine atoms in poly[(dichloro)phosphazene] by amines (Allcock et al, 1966). Drug molecules bearing an amino-group are substituted in the same way, such as the anesthetic molecules procaine, benzocaine, chloroprocaine, butyl-p-aminobenzoyl and 2-amino-4-picoline (Allcock et al, 1982). The poly [(diamino) phosphazene] is not water soluble but this can be achieved by cosubstitution with methylamine, procaine or 2-amino-4-picolino. 

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