THE CONDENSATION OF ALDEHYDES WITH MALONIC ACID IN THE PRESENCE OF ORGANIC BASES.

Part II. The Condensation of .

BY AzI~I< ALl KHAN, 1VI.SC., P. N. KURIEN, M.SC., AND K. C. PANDYA, M.A., P~.D., D.I.C., Cl, emieal Laboratory, St. John's College, Agra. Received Decembe~ 8, 1934.

KNO~VENAGELI (1898) brought about the condensation of salicylaldehyde with malonic acid in the presence of a minimum quantity of piperidine, with tile formation of -carboxylic acid. Butt 2 reported (1925) a conden- sation " in presence of piperidine in pyridine solution" with a poor yield of o-coumaric acid. In Part I of this series, it has been shown (Kurien, Pandya and Surange, 3 193~) that (I) the simpler aromatic aldehydes could be condensed with malonic acid in the presence of pyridine alone and without the piperidine, the base, the acid and the aldehyde being in equimolar proportions, and the yields, under suitable conditions, could be up to 96% of theory; that (2) under the same conditions the aromatic hydroxy-aldehydes, including salicylaldehyde, showed no condensation at all; but that (3) the condensation did occur, with yields up to 57~ of coumarin-carboxylic acid, if traces, instead of molecular quantities, of pyridine were used ; and that, lastly, in the condensations of other aldehydes also the trace of pyridine was equally, if not more, efficacious (piperonal giving 100% yield, in contrast with the 76% reported by Dutt2). In the present paper the study of this condensation is extended to the use of other organic bases in place of piperidine or pyridine, such as have not been hitherto tried, viz., lutidine, quinoline, iso-quinoline, a-naptho- quinoline, quinaldine, cinchonine, dimethylaniline, diethylaniline, benzyl- methylaniline, and methylacridine : the aldehyde being in all cases salicylaldehyde. A preliminary experiment, under conditions of maximum yield with pyridine, but without the use of any base or another reagent, was tried. It

1 Knoevenagel, Bet., ]898, 31, 2585. 2 Butt, Jour. Ind. Chem. See., ]925, 1, 298, 300. S Kurien, Pandya and Surange, Jour. Ind. Chem. Soc., ]934, 11,823. 440 T,~e Cozdemaiion o/ AMe@des 441 showed that salicylaldehyde and malonie acid alone, on heating :[or five hours at 100 ~ C. and then keeping overnight, reacted with the formation of the usual coumarin-carboxylic acid (m.p. 187-188~ but the yield was only 11% of the theory. A detailed examination with varying molecular proportions of lutidine added to the acid and the aldehyde, was undertaken. The observations (Table I) show that there is no condensation when the base is from 1 to 0.2 mole. Indeed, when full molar proportions are tried, carbon dioxide is given out as soon as heating is started. As this never happens when the condensation results in the formation of coumarin-carboxylic acid, it is clear that, if there is any condensation in this case, the product should be either eoumarin or o-comnaric acid. None of these is, however, to be found at the end, while the reaction mixture gives back ahnost all the aldehyde, the base and acetic acid. When the base was in lesser proportion, the usual condensation-product made its appearance in increasing amounts till under the most favourable conditiorts, the yield rose to 74%(Table I). The other bases were used on the same principle, the product in all cases being the same coumarin-carboxylic acid, which, though slightly and differently coloured, was always pure enough to give tile same melting point and good analysis. The yields are comparable, in many cases favourably, with the figures obtained by Dalal and Dutt ~ who employed molecular quantities of bases with aldehydes. Though salicylaldehyde does not occur in their table, it is remarkable that methyl- acridine gives them with their lowest yield (1-3%), and the same base gives us with salieylaldehyde our highest (77%). Knoevenagel thinks that the aldehyde combines first with the base piperidine which then reacts with malonic acid. It has been found while the experiments described in Part I were in progress, that pyridine and malonic acid when warmed together in molecular proportions gave a white solid product which analysis showed to be pyridine malonate and which, after isolation, could also be used irt condensations with benzaldehyde. Ouinoline malonate has also been obtained in the same way and decomposes just above its melting-point, 90 ~ C., giving off carbon dioxide, acetic acid and the base. When, however, it is mixed with salieylaldehyde, the decomposition starts even at 50 ~ C. As the temperature of the condensation is higher, 80 ~ C. or so, no condensation is thus possible. The decomposition is avoided when malonic ester is used in place of

4 Dalal and:Dutt, ,lmtr. fnd. Chem. Soc., 1932, 9, 309. 442 Azhar Ali Khan and others the acid, and then, as other investigations to be reported in Part III show, the condensations take place even when 0.5 mole. of the base is present. Experimental. Condensatio.~ ~,it.hout a base.--5 grams malonie acid (Sch. Kahl Baum, pure for scientific purposes, dried at 100 ~ C., and kept in a desiccator) and 6 c.c. of salicylaldehyde (Merck, pure synthetic) were mixed and kept in a dry flask on the water-bath at I00 ~ C. for 5 hours and then left overnight to cool. The product, acidified with hydrochloric acid, was steam-distilled till the remaining aldehyde was removed. Tile contents of the flask were taken out and cooled; crystals separated, which on drying and after a recrystallisation from alcohol, melted at 187-188 ~ C. The yield was 11% (Table I). Condensations with lutidir~e.--The same experiment was repeated with different proportions of purified and redistilled lutidine and later with different conditions of heating, etc. (Tables I and II). The highest yield was 74%, obtained with 0.05 mole. (0-25 c.c.) of lutidine, on heating at 800 C. for 12 hours and then keeping it for a week at the ordinary temperature. Condensations with quir~oline.--The acid and the aldehyde were heated together on a water-bath till the acid passed in solution. The base was then added and the mixture kept at laboratory temperature (15-20 ~ C.) for some time and then heated on water-bath for definite time (Table III). Condensations in the presence of the remaining bases were carried out in the same way, the results and details are given in Tables IV and V (isoquinoline in Table IV and all the bases in Table V). The identity of the product was confirmed not only by comparison with known samples, but also by analysis. The equivalent weight (by titration against standard baryta) was 190- 5. Found : C, 62.6~ I-I, 3.19% ; C10H604 requires 190-0, 63-1%, and 3-25 % respectively. The ComlemaXion of ZlMe@des 443

TABLE I.

Temp. of Quantity of Base Time of Yield Yield hea~ing h eating Remarks % C. I-Iours Grams C.CS. M ol. Prop.

0.00 0'00 i00 ~ 5 Kept, over- 1 11 night after heating. 2 0.05 O'O1 2.8 31

3 0.1 0.02 4.1 45

4 0.15 0.03 5,1 56

5 0.2 0.04 4.5 50

6 0"25 0.05 4.5 50

7 0-5 0,1 2.3 25

8 0.5 0.1 ~ 6 2.2 24

9 0.5 0.1 2.3 25

10 0"5 0.1 2.1 23

11 1.0 0.2 ~ 5 0 0

12 2"0 0.4, 0 0

13 3.0 0.6 0 0

14 4"0 0.8 0 0

15 5-0 1"0 0 0

16 0.25 0.05 Kept for 7 5.3 58 days after heating. 17 0.25 0.05 60 ~ 10 Kept over- 4.5 50 night after heating. 18 0.25 0-05 60 ~ 12 4.8 53

19 0.25 O.O5 60 ~ 15 4.8 53

20 0'25 0-05 80 ~ 12 6 66

21 0"25 0.05 80 ~ 15 6 66

22 0.25 O. 05 80 ~ 12 Kept for 7 6.6 74 days after heating. 444 Azhar Ali Khan and others

TABLE II.

Quantity of Base of Temp. Time Time of Yield C. heating keeping % C.(~S. Mol. Prop. Hours

1 0.5 0.1 60 ~ 10 15 days 66

2 0"25 0.05 100 ~ 5 30

3 0.25 0.05 60 ~ 10 5 ~ 50

4 0-25 0.05 800 10 5 ~ 66

5 0-25 0.05 80 ~ 10 64

TABL~ III.

Quantity of Base Temp. Time of Yield Yield C. heating Grams % }Iours C.C8, ~ol. Prop.

1 0"05 O. 008 100 ~ 5 2.8 31

2 0-1 O. 016 4-5 50

3 0.15 O. 02-i 4.8 53

4 0.2 O. 032 4.5 50

5 0"25 0.04 4.5 50

6 0.5 0.08 2-5 28

7 1 0.16 1.0 11

8 2 0.32 0.0 0

9 3 0.48 0-0 0

10 4 0.64 0.0 0

11 6.4 1 0.0 0

12 0-25 0.04 80 ~ 11 6.0 66 The Condensation o/./1/de/ ydes 445

TABLE IV.

Quantity of Base Time of t_ Temp. Yield Yield C. heating Grams % C.CS. Mol. Prop. 1tours

1 0.]5 0.024 I00 ~ 5 4.5 50

2 0.2 0,032 4.5 50

3 0.25 0.04 77 4.8 52

4 0.5 0.08 3 33

5 0'25 0.04 80 ~ 12 6 66

TABLE V.

Quantity of Base Yio,ld at Yield at Co]our Base 100~ 80~ of C.CS. 1Y~ol. Prop. Product

1 Lutidine 0.25 0.05 55 66 White

2 Quinoline 0,0t 50 66

3 Iso-Quinoline . 0-04 52 66 ~7

4 a-Naphtho- Quinoline 55 66 Grey

QuinMdine 0.037 55 66 White

Di-methyl- aniline ~7 0"04 60 74 Green

7 Di-ethyl-~niline 77 0' 03 60 72 Green

8 Cinchonidine . 25 Grams 0. 016 55 66 Yellow

9 Benzyl-methyl- aniline 0.025 55 66 Green

10 Acridine .. 0" 028 58 72 Yellow

11 Methyl-acridine 0. 026 60 77 Grey