3384 DEY AND DALAL : DIAZO-TRANSFORMATIONS OF

CC CXCIX. - D iaxo - transf ormations of Amino - coumarins and Aminonaphthapyrones. By BIMAN BIHARI DEY and HARIDAS DALAL.

IT is not possible to introduce a halogen atom directly into the benzenoid part of the coumarin molecule, because the substitution occurs in the lactone ring, which is more susceptible to attack. Thus, by the halogenation of coumarin, Perkin (this Journal, 1871, 24, 37) obtained a monochloro- and a monobromo-derivative containing the halogen in the pyrone ring ; the isomeric derivatives with the halogen in the benzene nucleus were prepared synthetically by the action of acetic anhydride on the sodium salts of the corre- sponding halogenated salicylaldehydes. Similar results have been recorded by Seidel (J. pr. Chern., 1898, [ii], 57, 495), Simonis and Wenzel (Ber., 1900, 33, 1961), and also, in the case of several hydroxy-coumarins, by Fries and Lindemann (AnnaEen, 1914, 404, 65) , who showed that under normal conditions no derivatives could be obtained in which the halogen had been exclusively substi- tilted for hydrogen atoms in the benzene ring. Compounds of

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AMINO-COUMARINS AND AMMONAPHTRAPYRONES. 3385

the latter class, of which only a few are described in the literature, have hitherto been prepared, usually in poor yields, by indirect processes such as the application of Perkin's reaction to halogenated salicylaldehydes, or the condensation of halogen-substituted phenols with malic acid and acetoacetic ester (Pechmann).

The diazo-transformation of aminocoumarins, which are readily obtained by the nitration and reduction of coumarins, does not appear to have been employed to any extent in the preparation of these Bz-substituted coumarins. Our attention was first directed to the subject in the course of a determination of the positions of the halogen atoms in certain chloro- and bromo-a-naphthapyrones, which were subsequently prepared in good yields from the corre- sponding amines. The reaction was therefore investigated more fully and the results were applied in several cases to the orientation of substituents in coumarin derivatives.

Aminocoumarins behave like substituted benzenoid amines, the lactone ring having no influence on the course of the diazo-trans- formations (compare Morgan and Micklethwait, T., 1904, 85, 1233). Some of these diazo-derivatives are extraordinarily stable ; for example, a solution of 4-methyl-~-naphthapyrone-6-diazonium sulphate retains in full its power of coupling with p-naphthol or aniline even after standing a t the laboratory temperature (32") for two weeks. 6-Aminocoumarin, 6-amino-a-naphthapyrone, and some of their alkyl homologues gave excellent yields of the corre- sponding chloro-, bromo-, and iodo-derivatives on the usual treat- ment ; in several cases, the products were identified with compounds obtained by Perkin's reaction. The cyano-derivatives, which were also prepared in the usual way, exhibited the general charac- teristics of aromatic nitriles and were hydrolysed with ease to coumarincarboxylic acids. They also condensed with ethyl alcohol under the influence of dry hydrogen chloride to form the corre- sponding imino-ethers. When the imino-ether hydrochloride obtained from 6-cyanocoumarin was carefully heated under reduced pressure, it was quantitatively transformed into coumarin-6-carb- oxylamide :

C,H,O,.C(OEt):NH,HCl --+ C,H,O,.CO*NH,+EtCI. The reaction furnishes a simple method for the preparation of the acid amides of the coumarin series.

Coumarin-6-carboxylamide forms a white, insoluble silver salt which, like silver benzamide, reacts in the tautomeric form, as it is converted on digestion with cold ethyl iodide into the free imino- ether :

C,H,O,.CONH, -+ C9H,0,*C<$% -+ C,H,O,.C GNH OEt

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3386 DEY AND DALAL : DIAZO-TRANSFORMATIONS OF

The direct action of halogens on certain alkylcoumarins and naphthapyrones was also studied in the course of the present investigation. When 4 : 7-dimethylcoumarin is chlorinated or brominated, the first halogen atom to enter attaches itself to the pyrone ring in accordance with the usual rule. This is proved by (1) the behaviour of the compounds with alcoholic potash, which removes the halogen atom with the formation of 2 : Ldimothyl- coumarilic acid, (2) the identity of the monochloro-derivative and the product of condensation of m-cresol and ethyl a-chloroaceto- acetate (Dey, P., 1914,30, 38). On further chlorination, a dichloro- derivative is produced which loses a molecule of hydrogen chloride and yields a monochlorodimethylcoumarilic acid when treated with boiling alcoholic potash in the usual way. The second atom of chlorine is therefore evidently attached to the benzene ring. Its position was determined in two ways, (1) by the preparation of the same compound from 6-amino-4 : 7-dimethylcoumarin by the diazo-transformation and further chlorination of the product, (2) by its synthesis from 6-chloro-m-cresol and ethyl a-chloroaceto- acetate as shown in the following scheme :

0 0 0

0 I.

0

Chlorination of 4-methyl- 1 : 2-a-naphthapyrone is analogous to that in the previous case. The first product is a monochloro- derivative in which the halogen has entered position 3 in the pyronc ring, the substance being identical with the compound obtained by the condensation of a-naphthol with ethyl a-chloroacetoacetate ; alcoholic potash converts it into 2-methyl-a-naphthafuran-1-carb- oxylic acid (Hantzsch and Pfeiffer, Ber., 1886, 19, 1303). On further chlorination, a dichloro-derivative is obtained, thc 6-position of the second chlorine atom being established, as in the previous case, by preparing the same compound from diazotised 6-amino- 4-methyl-a-naphthapyrone and cuprous chloride and subsequent chlorination.

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AMINO-COUYARINS AND AMINONAPHTHAPYRONES. 3387

E X P E R I M E N T A L . 0

')'lg.-An ice-cold solution of

6-aminocoumarin (2 grams) in 4N-hydrochloric acid (25 c.c.) was diazotised and, after one hour, added gradually to an ice-cold solution of cuprous chloride (2 grams) in concentrated hydrochloric acid (15 c.c.). The mixture was shaken for a few minutes and then gradually heated on the water-bath until effervescence ceased. The precipitate obtained on cooling was washed with very dilute caustic soda solution and with water, dried, and extracted with hot alcohol. Recrystallisation from rectified spirit gave a mass of pale yellow needles, m. p. 163" (Clayton, T., 1908, 93, 2022, gives m. p. 162"), weighing 1.7 grams (75 per cent. of the theoretical) (Found : C1 = 20.06.

The yield of the recrystallised product, m. p. 160" (Perkin, T., 1871, 24, 41), was 1.3 grams or 47 per cent. (Found: Br = 35-27. Calc., Br = 35.56 per cent.).

6-Iodocoumarin.-The ice-cold diazo-solution prepared from 6-aminocoumarin (2 grams) was slowly treated, with constant stirring, with a solution of potassium iodide (26 grams) in 20 C.C.

of water. A yellow, crystalline mass formed after a short time, which gradually turned brown owing to separation of iodine. After the usual heating on the water-bath, the product was treated with a few crystals of sodium bisulphite until the colour became light yellow, cooled, filtered, and crystallised twice from absolute alcohol, 6-iodocoumarin (1.5 grams) being obtained ih fine, colour- less needles, m. p. 165" (Seidel, J. pr. Chem., 1898, [ii], 57, 496, gives m. p. 164") (Found : I = 46.43.

6-Cyaizoccrumarin.-This compound was prepared from the diazotised amine (4 grams) and a solution of cuprous cyanide (potassium cyanide, 8 grams, cryshllised copper sulphate, 7 grams, water, 40 c.c.) a t 50". A yellow, crystalline deposit soon formed which turned reddish-brown towards the end of the operation. The mixture was heated to 100" and the solid collected after twelve hours, dried, and extracted repeatedly with boiling rectified spirit. The crystals which were first deposited were pale brown, but two crystallisations from 50 per cent. alcohol furnished long, colourless needles, m. p. 220". The yield was 2.6 grams (Found : C = 70.5 ; H = 3.44 ; N = 8.16. C,,H,O,N requires C = 70.2 ; H = 2.92 ; N = 8.18 per cent.).J

clL\/ 6-Chlorocoumnriia,

CH

Calc., C1 = 19.67 per cent.). 6-Bromocoumarin was prepared in a similar way.

Calc., I = 46.69 per cent.).

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3388 DEY AND DALAL : DIAZO-TRANSFORMATIONS OB

Coumarin-6-car~oxylic Acid.-6-Cyanocoumarin was warmed with 70 per cent. sulphuric acid until effervescence ceased. The flocculent precipitate which formed on pouring the product into cold water was dissolved in dilute sodium carbonate solution and reprecipitated with acid. It was deposited from dilute alcohol in fine, colourless needles, m. p. 268". Stormer and Oetker (Ber., 1904, 37, 194), who prepared it by oxidation of the aldehyde, gave the same melting point (Found : C = 62.67 ; H = 3.19. Calc., C = 63.15 ; H = 3.15 per cent.). The free acid is sparingly soluble in hot water, and the aqueous solution of the sodium salt exhibits a pale blue fluorescence.

The ethyl ester was obtained from the acid in the usual way, but was more conveniently prepared by saturating a solution of the cyanocoumarin in excess of cold absolute alcohol with dry hydrogen chloride. After twelve hours, the solution was poured into cold water. The precipitate, crystallised once from 50 per cent. alcohol, formed soft, white needles, m. p. 130", the yield being almost theoretical (Found : C = 65.7 ; H = 4.98. C12Hlo0, requires C = 66.1 ; H = 4.59 per cent.).

Chloride of Coumarin-6-carboxylic Acid.-The acid (2 grams) was boiled under reflux with phosphorus trichloride (5 c.c.) and phosphorus pentachloride (1 gram) until the solution became clear. The excess of phosphorus chloride was distilled off and the residue poured over crushed ice. A dark oil separated which quickly solidified. It was dried on porous tile, and crystallised from a minimum of boiling chloroform. The substance began to shrink a t 175" and melted completely a t 182" (Found: C1 = 16.64. CloH,O,C1 requires C1 = 17.02 per cent.).

The anilide, prepared by warming the above acid chloride and aniline together for a minute, separated from glacial acetic acid in shining crystals melting at 194" (Found : K = 5.0. C,,H1103N requires N = 8.28 per cent.).

0 Coumarin-6-formiminoether Hydroddoride,

-6-Cyanocoumarin (2 grams) was made into a thin cream with absolute alcohol (45 c.c.) and the mixture saturated with dry hydrogen chloride a t 0". The flask was loosely corked and left over-night a t the laboratory temperature; about 60 C.C. of dry ether were then added with vigorous shaking. The crystals that separated after some time were washed with ether, and dried in

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AMINO-COUMARINS AND AMINONAPHTHAPYRONES. 3389

a vacuum over lime. The hydrochloride was readily soluble in cold water (Pound : C1, by iitration with N/lO-silver nitrate, = 14-5. Cl,H,,03NC1 requires C1 = 14.00 per cent.).

The free imino-ether was obtained in fine, glistening needles by the action of ammonia on the aqueous solution of its hydrochloride. It melted a t 135" and was very soluble in alcohol (Found: N = 6.43. Coumarin-6-carboxylamide.-The imino-ether hydrochloride (2

grams) was heated in a 50 C.C. distilling flask connected to the water-pump. At 170-180", long, white needles began to sublime. The temperature was gradually raised to 200" and a t the end of the reaction the product was digested with alcohol and the extract filtered and evaporated to dryness. The residue was crystallised from hot water, colourless prisms, m. p. 203", being obtained with the aid of animal charcoal. The pure product weighed 0.9 gram (Found : N = 7.27.

Preparation of the Imino-ether from the Silver Salt of the Amide.- The silver salt, which was obtained as a white, granular precipitate on adding silver nitrate to an aqueous solution of the amide, was dried on porous tile and boiled with excess of ethyl iodide under reflux for three to four hours. The liquid was evaporated on the water-bath, and the residue crystallised twice from dilute alcohol. The product melted at 134-135") alone or mixed with the imino- ether (m. p. 135") prepared above.

Coumarin-8-formamidine Hydrochloride, C,HSO,.C(:NH)*NH,,HCl. -The imino-ether hydrochloride was triturated with alcoholic ammonia until nearly the whole of the solid dissolved. The filtered solution was evaporated in a vacuum a t the ordinary temperature, the residue treated with hydrochloric acid, and the solid crystallised from a little dilute hydrochloric acid, when a mass of woolly needle, separated, which became waxy and translucent a t 130", and melted to a clear liquid a t 170-171".

6-Chloro-4 : 7-dimethyZcoumarin.-This compound, prepared from diazotised 6-amino-4 : 7-dimethylcoumarin and cuprous chlorides crystallised from absolute alcohol in pale yellow prisms, m. p. 210", the yield being almost quantitative (Found : C1 = 17-21. C,,H,O,Cl requires C1 = 17.02 per cent.).

6-Cyano-4 ; 7-dimethyZcoumarin, obtained in poor yield from the 6-amino-compound in the usual way, crystallised from acetic acid in soft, buff-coloured needles, m. p. 286".

3-Chloro-4 : 7-dimethylcoumarin.-The required amount of dry chlorine, generated from potassium permanganate and hydro- chloric acid, was passed into a boiling solution of the coumarin in glacial acetic acid. Magnificent, prismatic needles separated from

C,,H,,O,N requires N = 6.45 per cent.).

C,,H,O,N requires N = 7.41 per cent.).

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3390 DEY AND DALAL : DIAZO-TRANSTORMATIONS OF

the cold solution. These contained acetic acid of crystallisation, which was lost on exposure to the air. The resulting powder, recrystallised from alcohol, gave long, colourless needles, m. p. 134" (Found : C1= 16.89. C,,H,O,Cl requires C1= 17.02 per cent.).

2 : 5-Dimethylcoumarilic acid, prepared from the above mono- chloro-derivative, crystallised in thin needles melting a t 218". The silver salt was prepared (Found : C,,H,O,Ag requires Ag = 36.36 per cent.).

3 : 6-Dichloro-4 : 7-dimethylcoumarin was prepared by saturating with chlorine a warm glacial acetic acid solution of either 3-chloro- or 6-chloro-4 : 7-dimethylcoumarin, and being very sparingly soluble, separated in the crystalline form. Recrystallisation from excess of boiling glacial acetic acid gave long, prismatic needles, m. p. 216" (Found : C1= 28.98. C1,H80,Cl,requires C1= 29-21 per cent.).

The same compound was synthesised by Pechmann's method as follows : 6-chloro-m-cresol (7 grams) and ethyl a-chloroaceto- acetate (8 grams) were 'treated a t 0" with concentrated sulphuric acid (10 c.d.), and the mixture, having been left over-night a t the laboratory temperature (30°), was poured into 300 C.C. of cold water. The solid that separated was crystallised several times from hot alcohol, and prismatic needles were obtained, which weighed more than 2 grams, melted a t 216", and did not depress the melting point of the preceding compound.

4-chloro-2 : 5-dimeth~lcouniarilic Acid.-The potassium salt of this acid separated out on boiling the dichloro-compound mentioned above with excess of alcoholic potash under reflux for three hours ; it was crystallised from the minimum amount of hot water (Found : K = 14-81. C,,H,O,CIK requires K = 146 per cent.). The free acid crystallised from dilute acetic acid in felted needles melting with decomDosition a t 264-265".

Ag = 36-36.

z

6-Amino-1 : 2-a-naphthapyrone, NH,*C,,H,<CH:

alcoholic solution of stannous chloride (9 grams) and concentrated hydrochloric acid (8 c.c.) containing a little metallic tin was slowly treated with the 6-nitronaphthapyrone (2 grams). The mixture having been boiled under reflux for an hour and cooled, 10 C.C. of concentrated hydrochloric acid were added, and, after a few hours, the crystalline stannichloride was collected, washed with a little concentrated hydrochloric acid, and boiled with sodium acetate solution (10 grams in 500 c.c.). The amine, which separated as a yellow powder after twelve hours, was purified by crystallisation from alcohol, golden-yellow needles, m. p. 193", being obtained (Found : N = 6-58. C,,H,O,N requires N = 6-64 per cent.). The amine formed a sparingly soluble hydrochloride, nitrate, and sulphate which crystallised well from hot water.

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AMINO-COUMARINS AND AMINONAPHTHAPYRONES. 3391

The acetyl derivative, prepared by boiling the amine with acetic anhydride containing a drop of pyridine for a minute, crystallised from alcohol in colourless needles, m. p. 216" (Found : N = 6-32. C1,H1,03N requires N = 5.53 per cent,). The benzoyl derivative formed colourless prisms, m. p. 239".

6-Chloro-1 : 2-a-naphthapyrone. - As the aminonaphthapyrone hydrochlorides are very sparingly soluble in water, diazotisation of the 6-amino-compound was effected by alternately adding the powdered amine and sodium nitrite to ice-cold hydrochloric acid. The mixture having been kept in the cold for two hours with occasional shaking, the almost clear solution was filtered and added slowly to the cold cuprous chloride solution ; the crystalline pre- cipitate obtained was treated in the usual way. Crystallised from glacial acetic acid, the product gave light yellow, prismatic needles, m. p, 106" (Found: C1 = 15.0. Cl3H,0,C1 requires C1 = 15.4 per cent.).

6-Chloro-4-methyl-1 : 2-~-naphthpyrone,-The amine (2 grams) was diazotised in the manner described above and treated with cuprous chloride. The product crystallived from alcohol in lustrous yellow needles, m. p. 212" (yield 1-5 grams) (Found : C1 = 14.3. C14H,0,C1 requires C1 = 14.51 per cent.).

6-Bromo-4-methyl-1 : 2-a-naphthpyrone crystallised from acetic acid in brown, prismatic needles, m. p. 210" (Found : Br = 27.4. Cl,HsO,Br requires Br = 27.68 per cent.).

6-Iodo-4-methyl-1 : 2-a-naphthapyrone, obtained in the usual way in almost theoretical yield, separated from alcohol in pale yellow, silky needles, m. p. 212" (Found : I = 38.47. C14H,0,1 requires I = 38.8 per cent.).

6-Cyano-4-methyl-1 : 2-a-naphthapyrone crystallised from alcohol in yellow needles, m. p. 273" (Found: N = 5.88. Cl,HsO,N requires N = 5.96 per cent.).

4-Methyl-1 : 3-a-naphthpyrone-6-carbory2ic acid was prepared by hydrolysing the cyano-compound with warm 70 per cent. sulphuric acid. It was deposited from dilute alcohol in clusters of colourless needles, m. p. 215".

3-Chloro-4-methyl-1 : Z-a-)zaphthpyrone.-Dry chlorine, generated from 4 grams of potassium permanganate, was passed into a boiling glacial acetic acid (50 c.c.) solution of the methylnaphthapyrone (6 grams). Crystals of the monochloro-derivative soon began to appear and filled the liquid on cooling. A single crystallisation from acetic acid yielded flat prisms melting a t 225", alone or mixed with a specimen of the 3-chloro-compound prepared from a-naphthol and a-chloroacetoacetic ester (Found : C1 = 14.94. C,,H,O,Cl requires C1 = 14.51 per cent.).

3 : 6-Dichloro-4-methyl-1 : 2-a-naphthupyrone was prepared by

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3392 OWEN: THE FREEZING-POINT CURVES OF BINARY

chlorinating either the 3-chloro-derivative described above or the 6-chloro-compound obtained by the diazo-reaction from the corre- sponding amine. It was practically insoluble in alcohol, but could be crystallised from a large quantity of boiling acetic acid, which deposited prismatic needles, m. p. 288" (Found : C1 = 24.97. C,,H,O,Cl, requires C1 = 25-45 per cent.).

PRESIDENCY COLLEGE, CALCUTTA. PRESIDENCY COLLEGE, MADRAS. [Received, OctobeT l e t , 1923.1

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