Piperazine N-methyl

One-tenth mol (20 g) of benzhydryl chloride was mixed with 0.19 mol (19 g) of N-methyl-piperazine and about 10 cc of benzene and the whole was heated on the steam bath four hours. The contents of the flask was partitioned between ether and water, and the ethereal layer was washed with water until the washings were neutral. The base was then extracted from the ethereal layer by N hydrochloric acid and the extract, made acid to Congo red paper, was evaporated under vacuum, 29.5 g of the pure dihydrochloride of N-methyl-N -benzhydryl piperazine was recovered from the residue by recrystallization from 95% alcohol melting above 250°C with decomposition. 

Chemical Name 8-Nitro-1,2-dihydro-2-(N-methyl-piperazin-1 -yl)methylene-6-(o-chloro-phenyl)-1 H,4H-imidazo-[ 1,2-a] [ 1,4] -benzodiazepin-1 -one methanesulfonate... 

Auch mit N-Methyl-piperazin modifizicrtcs Natrium-bis-[2-methoxy-athoxy]-dihydrido-aluminat reduziert Carbonsiiurccstcr mit hohen Ausbeuten zu Aldehyden1. 

Under microwave heating conditions compound 46 is obtained with reduced reaction time (1.5 h) and better purity. A dramatic improvement was achieved when 46 was treated with N-methyl piperazine in DMF in a sealed glass vessel. After 1 h under microwave irradiation, the N-methyl piperazino derivative 47 was obtained in 68 % yield. 

The amino group of 10H-benzo[i7]thieno[2,3-e][l,4]diazepin-4-amine 253 can be substituted with N-methyl piperazine by direct amination under thermal conditions (Scheme 53, Section 3.1.3 (1997BMCL25)). 

Formation of thiolactam 276 and its direct amination with N-methyl piperazine (1994JHC1053) is one of the routes to piprerazines 277 (Scheme 59, Section 3.2.3 (1992AF896, 2002JHC163)). Alternatively, 7-fluorobenzo[l7]thieno[2,3-/][l,4]oxaze-pin-10(9H)-one 279 undergoes chlorination and sequential amination to 277. 

The N-4-chlorobutyl benzodiazepine dione 221 (Scheme 46, Section 3.1.1.2 (1993MI249)) gives the piperazine derivative after amination with N-methyl piperazine. 

Clarke recently published the first microwave-accelerated Hiyama coupling [163,164]. It was noted that the availability and nontoxic attributes of the organosilicon reactants make them very attractive in synthesis, but their low nucleophilicity limits their potential. Microwave heating allowed aryl bromides and activated aryl chlorides to react under palladium catalysis using an electron-rich N-methyl piperazine/cyclohexyl phosphine ligand (Scheme 75). A vinylation reaction with vinyltrimethoxysilane was also reported [164],... 

Diarylpyrrole derivatives Catalyst pharmacophore Had difficulty predicting N-methyl piperazine and thiomorpholine derivatives. No numerical prediction data were presented Biava et al. (47)... 

In many reactions the simple saturated nitrogen heterocycles—piperidine, pyrrolidine, piperazine, and morpholine—behave simply as secondary amines that happen to be cyclic. They do the sorts of things that other amines do, acting as nucleophiles in addition and substitution reactions. Morpholine, for example, is acylated by 3,4,5-trimethoxybenzoyl chloride to form the tranquillizer and muscle relaxant trimetozine, and N-methyl piperazine can be alkylated in an S l reaction with diphenylmethyl chloride to give the travel-sickness drug cyclizine. 

Some work in our laboratories was also devoted to improve the preparation process of carbamoyl chlorides containing tertiary alkylamine functions,such as N-chloro-carbonyl, N -methyl piperazine hydrochloride. This carbamoyl chloride is for example used in the synthesis of the sedative and hypnotic pharmaceutical Zopiclone as shown in scheme 122 (Ref. 175). 

Scheme 122 Synthesis of carbamoyl chloride derived from N-methyl piperazine and its use in the preparation of Zopiclone.

N-(/3-Cyclohe l-j3-hydro -j3-phenylethyl) -N -methyl-piperazine methylsulfate... 

A dry Schlenk flask equipped with a rubber septum is evacuated and purged with nitrogen two or three times prior to the addition of dry diethylether, N-methyl-piperazine and then triethylamine. 

The aeylative cyclization of phenol with acetic anhydride was carried out over CeY type zeolites. The reaction mechanism is given in Fig. 4. At 380°C, the yield of 4-methyl coumarin was 75 % at 81% conversion of phenol. N-Methylpyrrolidine was synthesized from 1,4-butanediol and methylamine over Cr ZSM-5 and modified ZSM-5 catalysts at 300 C. The reaction mechanism is given in Fig. 5. The synthesis of a number of five- and six- membered heterocyclics have been depieted in Table 1. The reaction was carried out at 250-400°C at 30-80 hydrogen atm., under down-flow fixed bed conditions. The yield of N-methyl piperazine was 90% at 95% conversion over ZSM-5 catalysts. Similarly 2-methyl pyrazine and piperazine were synthesized from propylene glycol and ethylenediamine over HZSM-5 (Fig. 6). 

Quinoxalinones have been prepared by reaction of the dichloroacetyl derivative of o-phenylenediamine with either morpholine or N-methyl-piperazine in the presence of sulfur (Scheme 6). Treatment of 0-phenylenediamine with l,2-dichloro-l,2-diethoxyethane gives a small... 

Reduction of acids or esters to aldehydes. Diaminoaluminum hydrides, particularly those derived from secondary cyclic amines such as N-methyl-piperazine or morpholine, are useful for reduction of carboxylic acids or esters to aldehydes, without contamination by the corresponding alcohols. The reduction is carried out in refluxing THF (6-20 hr.). In general, 2 moles of reagent are used for each mole of substrate. The reduction is applicable to both aromatic and aliphatic esters. Yields are in the range of 50-85%,... 

Modification of SMEAH by addition of 1 equiv. of morpholine or N-methyl-piperazine provides a reagent that reduces esters to aldehydes. ... 

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