340 CHATTAWAY : INTRAMOLECULAR REARRANGEMENT IN

XXXVII I. -Intramolecular Reawangernent in Berizu- tives of the Aromatic Aminoketones.

By FREDERICK DANIEL CHATTAWAY.

THE acylchloroamino-derivatives of the aromatic ketones readily undergo the intramolecular rearrangement characteristic of aromatic chloroamides, in which the halogen radicle leaves the nitrogen and changes place with a hydrogen atom occupying an ortho- or para- position in the ring. The presence of the ketonic group does not, apparently, influence the rearrangement. As, however, the final transformation whereby both vacant positions are filled only takes place at a somewhat high temperature, the ketonic group becomes involved under the influence of the catalyst employed, uncryatallisable tarry substances are produced, and the yield of the disubstituted aminoketone is small.

By these intramolecular changes, a number of substituted amino- ketones have been prepared, which are not easily obtained by direct substitution, this reaction as a rule only yielding a tarry product from which no pure substance can be isolated.

The mode in which these substituted ketones are produced fixes their constitution, as in such transformations the halogen is known always to take up the para- in preference to the ortho-position, whilst the meta-position with respect to the amino-group is never assumed.

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DERIVATIVES OF THE AROMATIC AMINOKETOSES. 341

Transformation of Acet yl- p -ch loro aminoclce t opAen om into 3 - CMoro- p- m e t ylarninoacetophenone,

N Cl*CO*CH, NH*CO*CH,

\/ CO*CH,

\/ CO=CH,

This transformation slowly takes place when a solution oE the chloroamide in chloroform containing about 5 per cent. of acetic acid is allowed to remain at the ordinary temperature, light being excluded; the change is complete in about 14 days. On evaporating off the chloroform, a red solid is left from which 3-chZoro-p-acetyl- aminowetophenone can be obtained by repeated crystallisation from alcohol. This substance crystallises in slender, colourless prisms (m. p. 163').

0.3635 yielded 0,2520 AgC1. C1= 17.1'7. C,,H,,O,NCl requires C1= 16.75 per cent.

3-Chloro-p-acetyZchZoroaminocccetophenone, CH,*CO.C,H,Cl*NCI*CO*C~,,

was prepared by adding a solution of 3-chloro-4-acetylaminoaceto- phenone dissolved in alcohol to an ice-cold solution of potassium hypochlorite containing an excess of potassium hydrogen carbonate ; it was extracted by chloroform, and, to complete the action, the solution was repeatedly shaken with fresh hypochlorous acid. The compound crystallises from petroleum (b. p. 60--80°) in clusters of colourless, transparent plates (m. p. 56').

0.1746 liberated I = 13.S C.C. N/IO I. C1 (as NCl) = 14.01. C,,H,O,NCl, requires C1 (as NCI) = 14.41 per cent.

When dissolved in glacial acetic acid and heated, it undergoes trans- formation, but the quantity of the crystalline dichloro-transformation product which could be isolated from the tarry product of the action was PO small tha t it was not further studied.

3-Chlor~-p-arninoacetophenone, CH;CO*C,H,Cl*NH,, was pre- pared by hydrolysing the acetyl derivative by heating i t for four hours with a mixture of alcohol and concentrated hydrochloric acid and decomposing the hydrochloride of the base with caustic potash. It crystallises from a mixture of chloroform and petroleum in short, four-sided, colourless prisms (m. p. 92').

0.1959 yielded 0.1668 AgCl.

VOL. LXXXV. A A

C1= 21.05. C,H,ONCl require8 C1= 20.91 per cent.

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342 CHATTAWAY : INTRAMOLECULAR REARRANGEMENT IN

3-~h~oro-p-benxoy~am~noacstophelzone, CH,*CO C,H,Cl*NH*CO*c,B,,

3 -Ch loro - p-propion y Inminoacetophenone, crystallises from alcohol in slender, colourless needles (m. p. 132').

CH,*CO* C,H3C1*NH*CO*C2HS, crystallifies from a mixture of chloroform and petroleum in groups of slender, colourless needles (m. p. 115').

Transformation of Acetyl-p-chloroaminobenzop~~enone into 3-ChZoro- p-acetyla?ninobenzopherone,

NCl*CO CH, NH- CO CH,

- /\ I 1 \/

CO*C,H,

+ I q c 1

\/ CO*C,H,

This transformation takes place slowly under similar conditions to those which bring about the transformation of the acetophenone derivative. When the chloroamide dissolved in chloroform containing 5 per cent. glacial acetic acid was allowed to remain at the ordinary temperature and screened from light, it became completely trans- formed in about 14 days. On evaporating off the chloroform, a viscid, oily substance was left, which, however, solidified to a nearly colour- less mass on warming for a short time with a solution of potassium hydrogen carbonate. When repeatedly crystallised from alcohol, the pure 3-chloro-4-acety~arn~no6enzop?~enone, C6H5*CO*C6H,Cl*NH*C0 CH,, was obtained in colourless, rhombic plates (m. p. 99.5.).

C,,H,,O,NCl requires C1= 12.96 per cent.

C,H,-CO*C6H,C1*NC1 *Co*CH,, crystallises from a mixture of chloroform and petroleum (b. p. 60-80") in transparent, colourless plates (m. p. 102').

0.2440 gave 0.1265 AgC1.

3-Chloro-p-ucety Zchloroaminobenxopl~e~~one,

C1= 12.82.

0.3760 liberated I= 24.5 C.C. N/10 I. C1 (as NCl) = 11.55. C15Hl102NC12 requires GI (as NC1) = 11.51 per cent.

3-C~Eoro-p-aminoberxo~~~~one, C,H,=CO*C,H,Cl*NH,, was obtained by heating the slcetyl derivative for three hours on a water-bath with alcoholic hydrochloric acid and decomposing the hydrochloride of the base with caustic potash; it crystallises from a mixture of chloroform and petroleum in small, slender, colourless prisms (m. p. 1 4 0 O ) .

0.1942 gave 0.1209 AgC'l.

3-Chloro-p benxo yZamino6enxophenone, C,H,* CO*C6H,C1-N H*CO * C6H,,

C1= 15.39. Cl3Hl,ONC1 requires C1= 15.31 per cent.

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DERIVATIVES OF THE AROMATIC AMINORETONES. 343

is sparingly soluble in alcohol, from which it crystallises in colourless, flattened prisms (m. p. 126').

3-Ch Zoro- p-benzo yZe~lo~oanzinobenzo~henone, C6H5*CO*C6H3C1'NCl 0CO*C6H,,

crystallises from light petroleum in short, colourless, flattened prisms with domed ends (m. p. 123').

0.1404 liberated I = 7.5 C.C. N/10 I.

3- Cldos*o -p-propionykanzinobenxophenone,

C1 (as NC1) = 9.46. C,,H,,O,NCI, requires C1 (as NC1) = 9.58 per cent,

C, H 5* CO* C,H ,CL*rJH-CO *C,H,, crystallises from alcohol or a mixture of chloroform and petroleum in slender, colourless needles (m. p. 107.5').

3-Chloro-p-pl.opionyIchloroa~~nobenzop~~none, C,K,.CO*C,H3C1.NCl0CO* C,H,,

crystallises from a mixture of chloroform and petroleum i n colourless plates (m. p. 114").

0.2790 liberated I=l ' i .4 C.C. N/10 I. C1 (as NCl)= 11.05. C,6H,30,NCI, requires C1 (as NCl) = 11.01 per cent.

I 'ransformntion of AcetyZ-o-chloroami?zobenxophenone into 5-ChZoro- o-aeety Zcr,.Linobenxophenorae,

NC1- CO*CH, NH*CO*CH, --+ <)CO*C,H, ,

U1 \/

This compound does not become transformed nearly so readily as the corresponding para-derivative, and remains apparently unchanged in chloroform solution containing 5 per cent. of acetic acid for zt period sufficient for the complete transformation of the latter.

This transformation can, however, be effected, accompanied by some decomposition and the formation of tarry products, by dissolving the chloroamide in glacial acetic acid containing about 0.5 per cent. of hydrogen chloride and heating the solution in a sealed tube in a water-bath for a few hours. On pouring the product into water and washing with a dilute solution of potassium hydrogen carbonate in order t o remove the acid, a pale brown, tarry mass is obtained. On dissolving this in a little alcohol, the transformation product slowly separates in colourless needles.

The behaviour of all similar derivatives leaves no doubt tha t the chlorine passes almost exclusively into the para-position with regard to the acetylamino-group.

A A 2

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344 REARRANGEMENT OF THE AROMATIC AMINOKETONES.

5-ChZoro-o-acetyZa~~~inobenzop~~~~aone, C,H,*CO°CGH,C1*NH*CO.CH,, orystallises from alcohol in slender, colourless prisms (m. p. 117").

0.2103 yielded 0.1104 AgC1.

5-Chloro-o-acetylchloroamino6enzophenone,

C l = 12.98. CI,H1202NC1 requires C1 E: 12.96 per cent.

C,H,*CO.C,H,CloIYC1*CO'CH,, crystallises from a mixture of chloroform and petroleum in clusters of colourless plates (m. p. 107").

0.2599 liberated I= 16.8 C.C. N / l O I. C1 (as NCl) = 11.46. C,,H,,O,NCI, requires C1 (as NC1) = 11 -51 per cent.

5-ChZoro-o-amino benzophenone, C,H, CO 4 C,H,Cl ON H,. -The ace ty 1 derivative of this base is hydrolysed only with difficulty, and requires prolonged boiling with excess of alcoholic hydrochloric acid. 5-Chloro- 2-aminobenzophenone is readily soluble i n chloroform or alcohol, spar- ingly so in petroleum ; it crystallises from a mixture of chloroform and light petroleum in slender, yellow needles (m. p. looo).

Tvansfon,zation of 3-Chloro-p-acetyZc~Zoroanzi~zobenxop~enone into 3 : 5- Dic7Lloro-p-acetyla~nino6enxophenone7

NCl*CO*CH, NH*CO*CH,

-3- \/

CO-C,H, \/

CO*C,H,

The transformation of the acylchloroaminobenzophenones is exactly analogous t o tha t of the acylchloroamino-derivatives of the similarly constituted chloroanilines. The transforma tion of acetyl-p-chloroamino- benzophenone is eflected more readily than t h a t of acetyl-o-chloro- arninobenzophenone, and t h e transformation of the latter more readily than tha t of 3-chloro-p-acetylchloroaminobenzophenone. Even when dissolved in glacial acetic acid containing a little hydrogen chloride and heated at 100' for several hours, this compound undergoes no appreciable amount of transformation.

Intramolecular rearrangement, however, occurs when the solution is heated for some hours a t 130-140" ; after eight hours at this tem- perature, the chloroamide was found t o have completely disappeared. Ou diluting the product and adding a slight excess of potassium hydro- gen carbonate t o neutralise the acid, a pale yellow, viscid mass was obtained which was readily soluble in warm alcohol, the solution slowly deposl ting needle-shaped crystals of the transformation product. The yield, however, is small, a considerable quantity of a t a r ry sub- otance bein6 fosi-ne ],

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SEPARATION OF P-CROTONIC ACID FROM U-CROTONIC ACID, 345

3 : 5-~ic~~lo~o-p-acet~Z~nainobenxo~henone, C,H,*CO*CGH2C1,*NH.CO.CH,,

crystallises from alcohol in colourless, needle-shaped crystals (m. p. 1850).

0.1626 gave 0,1509 AgCl. C1= 22-94. C1,HllO,NCl2 requires C1= 23#02 per cent.

The constitution of the compound follows from its mode of pre- paration, as the chlorine atoms can only enter the ortho-positions with respect to the acetylamino-group.

3 : ~-~~ch~o~o-p-nce€y~ch~oroc6na~nobenxop~enone, C,H,* CO.C,H,Cl,*NCl- CO-CH,,

crystallises from a mixture of chloroform and petroleum in groups OF transparent, colourless plates (m. p. 118.).

0.1019 liberated I = 5 - 9 C.C. N/10 I. C1 (as NCI) = 10.26. C1,Hl,O,NCl, requires CL (as NCI) = 10.35 per cent.

3 : 5- Dichloro-p- amim~ benxophenone, C,H,- COO C,H2C 1 ;NH2, pre- pared by hydrolysing the acetyl compound by boiling with alcoholic hydrochloric acid, crystallises from alcohol in short, colourless prisms (m. p. 137").

ST. BAT1THOT,OJIEW'S HOSPITAL AND COLLEGE, LOXDON, E.C.

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