[CONTRIBUTION FROM
THE
DEPARTMENT OF CHEMISTRY, WORCESTER
POLYTECHNIC INSTITUTE ]
COKDEKSATION OF AMIDES WITH CARBONYL COMPOUNDS : BENZYL CARBAMATE WITH AROMATIC ALDEHYDES‘ T. R. LEWIS, JR.,F. R . BUTLER,
A . E. MARTELL2
AND
Received November 24, 1944
Martell and Herbst (1) recently showed that certain carbonyl compounds react when heated with benzyl carbamate as follon-s:
R
R
\ R’
/
NHCOOCHzCaH6
\ /
C=O f 2HzKCOOCH2C6H6 -+
+ HzO
C
R’
/ \
NHCOOCHZ CsHs
where R may be H or COOH, while R’ may be an aliphatic or aromatic group. This work extends the benzyl carbamate condensation t o a number of aromatic aldehydes not previously investigated. The reaction proceeded as expected with cinnamaldehyde, hydrocinnamaldehyde, 2-nitrobenzaldehyde1 4-nitrobenzaldehyde, 3-nitrosalicylaldehy-de, and 5-nitrosalicylaldehyde. In each case one mole of aldehyde condensed with two moles of benzyl carbamate and good yields were obtained. The reaction is illustrated in the case of 4nit robenxaldehyde. O z N D C H O
+ 2H2NCOOCHzCeHs--+ S H C 00 CH2 CeH6
HzO
0 2 N D C H ’
\
NHC 0 0 CHZ(28%
These reactions are summarized in Table I. Similar condensations were attempted with p-hydroxybenzaldehyde, salicylaldehyde, and vanillin. The desired derivative of p-hydroxybenzaldehyde was obtained in very low yield, while none of the desired product was obtained with salicylaldehyde, and vanillin. The formula of each product mas proved by nitrogen and molecular weight determinations. In the case of the derivative produced from p-hydroxybenzaldehyde, however, insufficient material was available for determination of the molecular weight. The condensation products were all found t o be high-melting 1 Abstracted from a thesis presented by Thomas R. Lewis, J r , to the faculty of Worcester Polytechnic Institute in partial fulfillment of the requirements for the degree of Master of Science. 2 Kow a t Clark University, Worcester, Mass. 145
146
LEWIS, JR., BUTLER, AND MARTELL
crystalline solids, quite soluble in ethyl alcohol and ethyl acetate, less soluble in toluene and benzene, and insoluble in water and ligroin. The low yields from the hydroxyaldehydes may be due to the inhibition of the reaction by chelation between the hydroxyl and carbonyl groups. Thus salicylaldehyde gave no condensation product at all. On the other hand, piperonal and anisaldehyde, containing similar donor groups, cannot undergo chelate ring formation, and undergo condensation in the usual manner. S-Nitrosalicylaldehyde was condensed with benzyl carbamate to determine if the competing chelation between the nitro and hydroxyl groups (I and 11) would leave the carbonyl group relatively free t o react.
CHO
I
I1
That such may be the correct interpretation is indicated by the fact that 3nitrosalicylaldehyde gave a 91 % yield of condensation product. From 5-nitrosalicylaldehyde, only a 35% yield was obtained. I n this case no chelate ring formation with the nitro group is possible, but it is conceivable that the tendency for intermolecular hydrogen bonding might assist in breaking down the chelate ring formed with the carbonyl group. However, more evidence must be obtained before any definite conclusions can be drawn. It has been demonstrated (1, 2) that condensation products of this sort may easily be reduced catalytically to the corresponding primary amine : NHC 0 0CH2 Cs Hg
H2
+ RCH/ \
+ RCHzNHz
+ N E + 2C02 + 2CeHsCHs
NHCOOCH2CsHs
These derivatives of aromatic aldehydes would therefore be of interest as offering a method for the synthesis of ring-substituted benzylamines. EXPERIMENTAL PART
Preparation of reagents. Benzyl carbamate was prepared by the method of Martell and Herbst (1). Cinnamaldehyde and hydrocinnamaldehyde were purified by distillation, while vanillin, p-nitrobenzaldehyde, and p-hydroxybenzaldehyde were recrystallized from benzene. The o-nitrobenzaldehyde was prepared according to the method of Thiele and Winter (3) and the 3- and 5-nitrosalicylaldehydeswere prepared according to the method of Miller (4).
BENZYL CARBAMATE AND AROMATIC ALDEHYDES
147
General procedure for condensation reaction. The procedure used for condensation reactions is essentially that of Martell and Herbst (1). I n all cases a ratio of 2.00 moles of benzyl carbamate to 1.05 moles of aldehyde was heated in a vacuum on the steam-bath until the reaction seemed to be completed. The progress of the reaction was usually observed as evolution of water and solidification of the reaction mixture. The isolation and purification of each derivative is described below and the analytical data are given in Table I. A’, A!‘-dicarbobenzoxycinnamylidenediamine. The reaction mixture of 4.3 g. cinnamaldehydt: and 9.7 g. of benzyl carbamate crystallized in 5 hours, but the reaction was allowed t o continue for a total of 10 hours. The white crystalline product was purified by recrystallization from benzene. IV N’-dicarbobenzoxyhydrocinnamylidenediamine. The reaction mixture of 3.3 g. of hydrocinnamaldehyde and 7.1 g. of benzyl carbamate solidified i n 30 minutes, but the reaction was continued for a total of 1.5 hours. The product was purified by repeated recrystallization from benzene. ~
TABLE I CONDENSATION PRODUCTS FROM BENZYL CARBAMATE ALDEHYDE
PBODUCT
__
N , N’-dicarbobenzoxycinnamylidenediamine N , N’-dicarbobenzoxyhyH y drocinnamaldehyde drocinnamylidenediamine N , N’-dicarbobenzoxy-22-Njtrobenzaldehyde ni trobenaylidenediamint N , N’-dicarbobenzoxy-44-Nitrobenzaldehyde ni trobenaylidenediaminf N , N’-dicarbobenzoxy-33-Nitrosalicylaldehyde nit rosali cy li de nedi ami nt N , ru“-dicarbobenzoxy-55-Nitrosalicylaldehyde nitrosalic ylidenediamint 4-Hydroxybenzaldehyde ?itN’-dicarbobenzoxy-4hydroxybenzylidenediami ne Cinnamaldehyde
% YIELD
-
Calc’d Found Calc’d pound ----
23
187
6.73 6.68 416
64
165
6.70 6.68 418 425
58
167.5 9.65 9.79 435 412
54
197
9.65 9.70 435 450
91
169
9.31 9.25 451
35
189
9.31 9.22 451 465
0.E 171
-
415
415
6.89 6.55 406 -
h’,N ’-dicarbobenzoxy-8-nitrobenzylidenediamine, The reaction mixture of 4.0 g. of orthonitrobenzaldehyde and 7.7 g. of benzyl carbamate was allowed t o react for 11 hours. No crystals appeared, but the reaction mixture became quite viscous. This was dissolved i n hot benzene and the white crystalline product that was obtained on cooling was purified by repeated recrystallization from toluene. R’,N’-dicarbobenzoxy-Q-nitrobenzylidenediamine, The reaction mixture of 5.3 g. of paranitrobenzaldehyde and 10.0 g. of benzyl carbamate solidified in 2 hours, but the reaction was allowed to continue for a total of 6 hours. The white crystalline product was purified by recrystallization first from benzene and then from toluene. hT,N’-dicarbobenzoxy-3-nitrosalicylidenediamine,The reaction mixture of 5.3 g. of 3nitrosalicylaldehyde and 9.0 g. of benzyl carbamate crystallized completely in 2 hours, though the run was continued for a total of 6 hours. The yellow crystalline product was purified by recrystallization from toluene. hr,N’-dicarbobenzox~-6-nitrosalicylidenediamine. The reaction mixture of 5.2 g. of 5nitrosalicylaldehyde and 9.0 g. of benzyl carbamate completely solidified in 30 minutes, b u t
148
LEWIS, JR., BUTLER, AND MARTELL
the reaction was allowed to proceed for a total of 2 hours. The product was purified by extraction with hot toluene. It may be recrystallized from ethyl acetate-petroleum ether. N , Nt-dicarbobenzoxy-4-hydroxybenzylidenediamine.The reaction mixture of 4.8 g. of para-hydroxybenzaldehyde and 11.2 g. of benzyl carbamate showed no solidification after 12 hours. The oil was dissolved i n hot benzene and a very small amount of white crystalline product was obtained by addition of ligroin. It was purified by recrystallization from toluene. Salicylaldehyde condensation. The reaction mixture of salicylaldehyde and benzyl carbamate showed no sign of crystallization after 98 hours. S o product was isolated from the yellow reaction mixture. Vanillin condensation. When vanillin and benzyl carbamate were heated for 74 hours, partial solidification took place but none of the desired product could be isolated from the reaction mixture. A small quantity of white crystalline material, melting sharply a t 182", was obtained, however. Its structure has not yet been determined; found: N , 3.22. SUMMARY
Benzyl carbamate was condensed n-ith cinnamaldehyde, hydrocinnamaldehyde, 2-nitrobenzaldehyde, 4-nitrobenzaldehyde, 3-nitrosalicylaldehyde, 5nitrosalicylaldehyde, and 4-hydroxybenzaldehyde. In each case one mole of aldehyde condensed with two moles of carbamate to form a highly crystalline, high-melting derivative. With the exception of the condensation with 4-hydroxybenzaldehyde, the yields were generally good. Apparently chelate ring formation between the carbonyl and phenolic groups may hinder the condensation reaction. WORCESTER, MASS.
REFERENCES (1) MARTELL AND HERBST, J . Org. Chem., 6, 878 (1941).
(2) BERGMANN AND ZERVAS, Ber., 66, 1192 (1932). (3) THIELE AND WINTER,Ann., 311,353 (1900). (4) VOX MILLER,Ber., 20,1928 (1887).
