AU427118B2 - Novel n, n-disubtituted -ethylenediamines - Google Patents

Description

25 91 1 71 The present invention is concerned with novel N,N- disubstituted-ethylenediamines

The novel N,lN-disubstituted-ethylenediamines provic by the invention can be generically formulated thus: B R

0-NH 2

(I) wherein R represents a lower-alkyl group and R1 represent

a chlorine or bromine atom or the nitro or trifluoro-

methyl group. The compounds of the present invention are useful as starting materials for the preparation of the

intermediate ethylenediamine compounds of the general ?ca.r 3.^fl formula II/, and from these, the'l,4-benzodiazepines of th<

general formula I, disclosed andmi-e d*in the specifical ion of Application No. 22,241/67 from which the present

application has been divided.

It will be appreciated that the term 'lower alkyl' i

used in this description and in the claims appended hereto

to mean a straight-chain or branched-chain alkyl group con taining from 1 to 7 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl and isobutyl. The preferred lower-alkyl groups are those containing from 1 to 4 carbon

atoms.

An especially valuable class of novel N,N-disubstitu

ethylenediamines provided by the invention comprises com-

pounds of formula I in which R1 represents a chlorine or bromine atom. An especially preferred NJ,N-disubs:tituted- ethylenediamine of formula I is that in which R represents

-2- 427.1 18

2 5, 911 71 the methyl group and R1 is in$-position and reprezcr.ents the a chlorine atom; that is to say, N-(4-chloro-phenyl)-i. methyl-ethylenediamine. The novel N,N-disubStituted-eethylenediaines provided by the invention can be prepared by treating an N-(lo-::er alkyl)-aniline of the general formula

R S NH-R

(II) wherein R and R1 have the significance given earlier, with ethyleneimine in the presence of an aprotic LEWIS acid boron trifluoride, titanium tetrachloride and aluminium chloride, but preferably aluminium chloride), and an inert organic solvent a hydrocarbon such as benzene or toluene). The temperature at which the foregoing treatment of an 11-(lower alkyl)-aniline with ethyleneimine is carried out is not critical, although it is preferred to operate at an elevated temperature, preferably at about the reflux temperature of the medium. The following Example illustrates the manner in which the novel N,N-disubstituted-ethylenediamines pro- vided by the invention can be prepared:

EXAMPIi A mixture of 63.8 g (0.5 mol) of 4-chloro-aniline and 114 g. (0.6 mol) of paratoluene-sulphonyl chloride in 400 ml of pyridine was stirred at room temperature overnight. Lost of the pyridine was then removed in vacuo. The residue was poured into 2 litres of ice water and the

-3- 427.1 18

25, 911' 71 tosylate extracted with ether. The ether was extracted

with 1-N sodium hydroxide, aqueous hydrochloride acid and water, dried over magnesium sulphate and concentrated.

The resulting oil was crystallized from ether to yield

l-tosylamino-4-chloro-benzene of melting point 119,50

120.5°0.

A mixture of 70.4.g (0.25 nol) of l-tosylamino-4-

chloro-benzene, 700 ml toluene and 0.3 mol of sodium meth-

oxide in 200 ml of methanol was stirred and heated under

reflux for 1 hour. After distilling off most of the methanol, 47.3 ml (0.5 mol) of dimethyl sulphate were added. The stirring and heating under reflux was then

continued for a further 5 hours. The precipitated sodium salt disappeared slowly. Excess dimethyl sulphate was

destroyed by heating under reflux for an additional

hours with 400 ml of 3-N sodium hydroxide. The phases were separated and the toluene was distilled off to leave a white crystalline residue. Recrystallization from ethanol

gave l-(iN-methyl-tosylanino)-4-chloro-benzene of melting point 920-93o0.

61.5 g (0.208 nol) of l-(N-methyl-tosylamino)-4-chloro-

benzene were added to 580 ml of sulphuric acid (specific

gravity 1.74) at 105 0 C. The mixture was stirred, heated up to 145 C. and kept at that temperature for 1 hour. After cooling, the solution was made strongly alkaline with

sodium hydroxide and the organic base extracted with

ether. The organic extract was dried over potassium

hydroxide'pellets, concentrated and the residue distilled

in vacuo to yield 4-chloro-N-methyl-aniline of boiling point 74°-75 0 C/0.7 mm Eg.

427.1 18

911 if7 14.1 g (0.1 mol) of 4-chloro-D'-Lethyl-aniline were added carefully and with cooling, to 13.3 g of aluminium chloride and 20 nl of dry benzene, in a 50 ml three-neck flask equipped with reflux condenser, dropping funnel and stirrer. After the addition had been completed, the mixture was heated until reflux commenced and kept at that temperature for a short period. 4.3 g (0.1 mol) of freshly distilled ethyleneimine were then slowly distile d into the reaction vessel from a small flask attached to -he former with a gas inlet tube by heating the flask. After the addition had been completed, ths reaction mixture was stirred for a further 0.5 hour and then poured on to 200 g of ice contained in a one-litre flask fitted with a con- denser. 50 g of solid potassium hydroxide were added to the resulting solid in small portions and the material was seen to pass into solution. It was then cooled and extracted three times with benzene. The combined benzene extracts were dried over potassium hydroxide pellets and concentrated. The residue was distilled in vacuo through a 10 cm VIGREX column to yield N-(4-chloro-phenyl)-N- methyl-ethylenedianine of boiling point 126°-127°0/0.05

mm Hg0

427.118

Claims (3)

1. 911 /71 The claims defining the invention are as follows: 1. An N,',-disubstituted-ethylenediaine of the general fcrmula

   R

   -II -0~H-CH -CH 2 2 -IEm

   (I) wherein R represents a lower-al1krl group and R represents a chlorine or bromine atom or the nitro or trifluoromethyl group.
2. 2. An M,,-disubstituted-ethylenedia ine as formulatec in claim 1, iwherein R' represents a chlorine or bromine atom.
3. 3. N-(4-ch oro-h enyl) -N-methyl- ethyl

   DATED this TYTy-FOUTUR I day of FEBIWARY, 1971 F.HOT-; 1JA ROCIE CO. AKtTIEN,-ESELLTjSCEFU

   -Patent Attorneys for the Applicant SPRUSOB 6: FERGUSON

   -6- 27.1 -6d 18