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Thermal condensation of some α-aminoacids with phthalic acid
231 Thermochimica AC&. 7 (1973) 231-239 Q Elsevier Scientific Publishing Company, Amsterdam - Printed in Belgium
THERMAL PHTHALIC
CONDENSATION ACID
S. GURRIERI
AND
OF
SOME
G+AMINOAC~S
W-I-t-H
G. SIRACUSA
Isrirufo di Chimica Generate ed Inorganica, Unicersifa di Cafania (ha&) (Received 21 May 1973)
The reaction kinetics of thermal condensations of glycine, DL-valine, DL-alanine and L-phenylalanine with phthalic acid are studied; the activation ener_gy of the reactions occurring in the investigated systems is determined. ResuIts indicate that the thermai condensation involves the formation of phthaIamic acids followed by ring closure to form N-phthalyl-aminoacids. The thermal behaviour of phthalic acid, gIycine, DL-vahne, DL-alanine, Lphenylalanine and of the corresponding N-phthaiyl-aminoacids is aIso reported. IF.TRODUCTTON
ExampIes of application of thermal analysis to organic reactions have become more and more frequent as a result of the introduction of controhed atmosphere techniques_ Several workers I-’ 2 have prepared N-phthalyl-aminoacids by melting a mixture of an aminoacid with phthalic acid or anhydride. King and Kidd’ ’ report the mechanism of the reaction for the formation of phthaIyI-Dr.-ghrtamic acid by the interaction of phthaiic anhydride and r_-ghxtamic acid in pyridine; this procedure involves the condensation of phthalic anhydride with the aminoacid foIlowed by ring closure of the intermediate phthalamic acid. We have carried out the thermal condensation of some N-phthaiyl-aminoacids directely in a thermoanalyzer, by reacting the corresponding aminoacid with phthalic acid. Before starting the proper measurements, preliminarly investigations were performed for phthahc acid, for each r-aminoacid and for each N-phthalyl-aminoacid in order to establish their thermaI behaviour under the same conditions as for the thermal condensations.
Materiak Reagent
grade phthalic acid, gIi_cine, DL-valine, Dr_-alanine and L-phenylalanine
(C. Erba R.P_) were used.
.
232 N-phthaIy!-&l-&e (m-p_ 197°C). N-phthalyl-Dr_-valine (m-p_ 106”C), Nphthaiyl-nr--aIanine (m-p. 16J’C) and X-phthaIy!-r_-phenylalanine (m-p. IW’C), employed as test materials were prepared as described in ref. 5 and were recrystallized severai times from 10 oib aqueous aIcohoI_ Previously ignited AI,O, (C. Erba R-P.) was used as the DT.4 reference mater% 2’7rermalanalssis and tlremzaicondensations They were carried out with a MettIer vacuum recording thermoanalyzer in dynamic nitrogen atmosphere (IO I!h), at different heating rates (0.5; 1; IS; 2; 4’C:min). Higher rates proved to be inappropriate because in these conditions more than one reaction takes place simuItaneous!y. 0.3 ml aluminium crucibles, In a!! experiments PtjPt-Rh 10 o/othermocoupIes, and the same specimen hoider (MettIer T-TD3) were employed. The following ,quantities were simultaneoudy recorded as a function of the temperature (I ‘C): total change in weight (TG), first derivatit-e of the change in weight (DTG) and dif%rentiaI thermaI anaiysis (DT_4). The thermal condensation reactions were performed by introducing into the ,thermoanaI_vzer, every time, a cIose!y powdered stoichiometric mixture of each x-aminoacid and phtha!ic acid (different stoichiometric ratios do not affect the shape of the thermal cun-es in the temperature range of the condensations)_ Infrared spectra They were performed photometer_ RESULTS
.‘.XD
in KBr peI!ets using a Perkin-Elmer
Mode! 257 spectro-
DISCLSSIOX
TJzemralbeizariourof reactants PJzthaJic acid Ihe zhermai decomposition
cf this reactant
(Fig.
1) in the 200-218%
range
gives a product, whose me!ting point and infrared spectrum correspond to those of phths!ic anhydride. In this temperature range the TG curve shows a weight loss of a mo!e of water; the corresponding DTA curve, in its turn, tiords two not very we11 separated endothermic peaks correspondin g to meIting (20S°C) and to water loss (21 S “Cl. The DTA cum-e is not suitab!e for the determination of the activation ener_q, therefore the value of this one (see Table 1) was caiculated applying Piloyan ef aZ.‘s’3 equation to DTG data. The phthalic anhydride is formed at a tempersture higher than its melting point and it vapourizes in the range 21&2&X as indicated by TG and by the endothermic DTA peak.
233
__*________ ---______________-_
:
I
:
._ i ; ;
‘-
I
-.
3 T,$ -----.-..______ -----------
- ._
*.
= 33.4 mg; heating rate = S’Cjmin. Fig. I. Thermal analysis of phthalic acid. Weight * of sampfe
234 TABLE
1
EXERGY E, (k ca1:-mole) FOUND PH-I-HALIC ACID AND FOR THE REACi-ION: ACID = PHTHALAMC ACID t HZ0
ACTIVATION
PhthAic acid Phthalic acid-g.Iycine Phtha!ic acid-Dr-vatine Phthzdic acid-rx-&mine PhthaIic acid-r_-phenykdmine
FOR THE DEHYDRATION PHTHALIC ACIDtAMINO-
OF
E.
Linear correlafion
29.2 32.1 26.4 41-g 36-S
0.999 0.999 0.998 O-999 O-998
Aminoacid Thermal analysis curves of glycine, DL-valine, DL-alanine and r_-phenylalanine give evidence that these aminoacids do not decompose respectively under 220, 275, 200 and 220°C. N-phthai)kminoacids The first thermal transformation for N-phthalyl-glycine, N-phthalyl-DL-valine, N-phthaIyl-DL-alanine and N-phthalyl-L-phenylalanine was the meIting observed respectively at 195, 1I 1, 162 and lS4’C; they all begin to decompose, with weight Ioss, respectively at 200, 160, 184 and 212X. Thermal condensalions The shape of TG and DTG curves (Figs. 2-5) indicates that all the aminoacidphthalic acid mixtures begin to react between 120-14O’C namely at a lower temperature than that required to convert phthalic acid into phthalic anhydride and to decompose the aminoacids. In any case the weight loss, amounting on the whole to two moles water, at low heating rates, occurs in two steps; the first one corresponds to 0.4-O-7 moies. Therefore the thermal condensation involves two consecutive reactions which became simultaneous when the first one rises the 4O-70%. The slope variation of TG curves at the first step indicates an induction period preceding the beginning of the second reaction. All attempts to separate compIeteIy the two reactions were useless even in isothermal conditions at the starting temperature of the first reactions. DTA curves deviate from the base line in the same temperature range of DTG ~curvesand afford always a singIe peak due to the sum of the enthalpic effects of the two reactions and of the melting of the reaction mixture. This last was observed with the aid of a Kofler hot stage microscope. All investigated systems, after Ioss of fwo moles of water, give thermal condensation products whose m-p- and infrared spectra are the same as that obtained with the relative X-phthaIyl-aminoacids prepared as test materials. To calculate the activation ener_g;y of the fu-st reaction Piloyan et aZ.‘s’ 3 equation was applied to DTG data; the obtained values are reported in Table 1. _(
235
i 140
I
I
150 Tempercttire
I
PC)
Fig. 2. Thermal behaviour of the system ture = 26.0 mg; heating rate = 1 ‘C/min.
I
:QO
phthalic
acid-glycine
(1-I).
Weight
of reactant
mix.
236
!
f
DTG ___-_ ____ -- __-__ -----_
; -.
.__--__-----______
- i
‘.
-.
_’
..!
ns ‘-‘!!
1
-_
,*. I
:r ,: i:
/ .’ i
;i ; g::
;
1-j i-cg/mir; i
D-!-A __-___-_______
r3U
Tenqeratwe
PC?
Fig. 3. Thermal bchavioui of the system Rure = 146.1 mg; heating race = 1 ‘C!‘min.
phthalic
acid-Ix_-vaiine
([:I)_
Weight
of reactant
mix
237
1
TG
!
I
! / :\,\-
!
+mg
i
i 1 i
\ \
i__E____ -. I -.
t
/
i
--a-
.-a,
\
\
% : . .
/”
\ %_,
\!
=;,‘\
.-
_ _- ------_
_____
-----
__
1
I
1 mc/min
+
I I
-l I‘_-m-_-m__ XA \*,< _------_________ _. *. . _#’ .. ; ,’ ;. i I .I 4 / ,I . 1 ;. , I i oJ$i I . r, % \ , . I 1 ,, I i .-\ _; * i ‘.* 1
Fig_ 4. Thermal behaviour of the system phthalic acid-Dr-alanine ture = 172-4 mg; heating rate = 1 “C;min.
(]:I)_
Weight of reactant mix-
238
‘i \ : !
_-
c-
_---------__________
.. :.
I
13c!
I
_I
150 Temperatw-e
(“C>
170
Fig- 5. Thermal khaviour of the system phthalic acid-r-phenylalaninc mixture = 138.0 mg; heating rate = I “C/min.
(I:l).
Weight of reactant
239
The therm31 behaviour of the investigated x-aminoacid-phthalic acid systems excludes the formation of phthalic anhydride and the successive condensation of this with the aminoacid; it can be explained admittin, 0 the formation of intermediate phthalamic acid foIlowed by the ring cIosure into X-phthalyl-aminoacid:
Over and above the first mechanism shouId require the activation energy of the first reaction to be independent of the nature of the aminoacid and equa1 to that of the formation of phthalic anhydride from the dehydration of phthalic acid. The different activation energy vaIues we have found (see Table 1) indicate the second mechanism to be the correct one_ ACKlr;OWLEDGEMEXi-
The financial support gratefully acknowIedged.
of this work by the Consiglio
Nazionale
delle Ricerche is
REFERENCES 1 D. A. Kidd and F. E. King, Xurure, I62 (1945) 776. 2 J. C. Sheehan and V_ S_ Frank, J. Amer. Chenr. Sac., 71 (1949) 15%. 3 L. Reese. Ann.. 242 (I 987) I_ 4 %I_ Fling, F. N. hlinard and S. W. Fox, J. Amer. Chem. Sac., 69 (1947) 2466. 5 J_ H. Billman and W. F. Harting, I_ Amer. Chem. SOL, 70 (1948) 1473. 6 J. C. SheeSan, D. W. Chapman and R. W. Roth, J_ Amer. Chem. SOL, 34 (1952) 3S22. 7 R. S. Tipson. J. Org. Chem., 21 (1956) 1353. 8 J. C. Sheehan, M. Goodman and G. P. &ss. 1. Amer. Chem. SOL, 75 (1956) 13679 G. Wanag and A. Veinbergs. Chem. Ber., 7.5 (1942) 1558. 10 J. J. O’Neill. F. P_ Veitch and T. Wagner-Jauregg, J_ Org. Ckem., 21 (19%) 36_111 F. E King and D. A. Kidd, 1. Chcm. Sac., (1949) 3315 12 K. BalenoviC, B. Gaspert and N. Stimac, Croat. C,lem. Acta, 29 (1957) 93. 13 G. 0. Piioyan, I_ D_ Ryabchikov and 0. S. Novikova, .Vaiure, 214 (1966) 1229.
THERMAL PHTHALIC
CONDENSATION ACID
S. GURRIERI
AND
OF
SOME
G+AMINOAC~S
W-I-t-H
G. SIRACUSA
Isrirufo di Chimica Generate ed Inorganica, Unicersifa di Cafania (ha&) (Received 21 May 1973)
The reaction kinetics of thermal condensations of glycine, DL-valine, DL-alanine and L-phenylalanine with phthalic acid are studied; the activation ener_gy of the reactions occurring in the investigated systems is determined. ResuIts indicate that the thermai condensation involves the formation of phthaIamic acids followed by ring closure to form N-phthalyl-aminoacids. The thermal behaviour of phthalic acid, gIycine, DL-vahne, DL-alanine, Lphenylalanine and of the corresponding N-phthaiyl-aminoacids is aIso reported. IF.TRODUCTTON
ExampIes of application of thermal analysis to organic reactions have become more and more frequent as a result of the introduction of controhed atmosphere techniques_ Several workers I-’ 2 have prepared N-phthalyl-aminoacids by melting a mixture of an aminoacid with phthalic acid or anhydride. King and Kidd’ ’ report the mechanism of the reaction for the formation of phthaIyI-Dr.-ghrtamic acid by the interaction of phthaiic anhydride and r_-ghxtamic acid in pyridine; this procedure involves the condensation of phthalic anhydride with the aminoacid foIlowed by ring closure of the intermediate phthalamic acid. We have carried out the thermal condensation of some N-phthaiyl-aminoacids directely in a thermoanalyzer, by reacting the corresponding aminoacid with phthalic acid. Before starting the proper measurements, preliminarly investigations were performed for phthahc acid, for each r-aminoacid and for each N-phthalyl-aminoacid in order to establish their thermaI behaviour under the same conditions as for the thermal condensations.
Materiak Reagent
grade phthalic acid, gIi_cine, DL-valine, Dr_-alanine and L-phenylalanine
(C. Erba R.P_) were used.
.
232 N-phthaIy!-&l-&e (m-p_ 197°C). N-phthalyl-Dr_-valine (m-p_ 106”C), Nphthaiyl-nr--aIanine (m-p. 16J’C) and X-phthaIy!-r_-phenylalanine (m-p. IW’C), employed as test materials were prepared as described in ref. 5 and were recrystallized severai times from 10 oib aqueous aIcohoI_ Previously ignited AI,O, (C. Erba R-P.) was used as the DT.4 reference mater% 2’7rermalanalssis and tlremzaicondensations They were carried out with a MettIer vacuum recording thermoanalyzer in dynamic nitrogen atmosphere (IO I!h), at different heating rates (0.5; 1; IS; 2; 4’C:min). Higher rates proved to be inappropriate because in these conditions more than one reaction takes place simuItaneous!y. 0.3 ml aluminium crucibles, In a!! experiments PtjPt-Rh 10 o/othermocoupIes, and the same specimen hoider (MettIer T-TD3) were employed. The following ,quantities were simultaneoudy recorded as a function of the temperature (I ‘C): total change in weight (TG), first derivatit-e of the change in weight (DTG) and dif%rentiaI thermaI anaiysis (DT_4). The thermal condensation reactions were performed by introducing into the ,thermoanaI_vzer, every time, a cIose!y powdered stoichiometric mixture of each x-aminoacid and phtha!ic acid (different stoichiometric ratios do not affect the shape of the thermal cun-es in the temperature range of the condensations)_ Infrared spectra They were performed photometer_ RESULTS
.‘.XD
in KBr peI!ets using a Perkin-Elmer
Mode! 257 spectro-
DISCLSSIOX
TJzemralbeizariourof reactants PJzthaJic acid Ihe zhermai decomposition
cf this reactant
(Fig.
1) in the 200-218%
range
gives a product, whose me!ting point and infrared spectrum correspond to those of phths!ic anhydride. In this temperature range the TG curve shows a weight loss of a mo!e of water; the corresponding DTA curve, in its turn, tiords two not very we11 separated endothermic peaks correspondin g to meIting (20S°C) and to water loss (21 S “Cl. The DTA cum-e is not suitab!e for the determination of the activation ener_q, therefore the value of this one (see Table 1) was caiculated applying Piloyan ef aZ.‘s’3 equation to DTG data. The phthalic anhydride is formed at a tempersture higher than its melting point and it vapourizes in the range 21&2&X as indicated by TG and by the endothermic DTA peak.
233
__*________ ---______________-_
:
I
:
._ i ; ;
‘-
I
-.
3 T,$ -----.-..______ -----------
- ._
*.
= 33.4 mg; heating rate = S’Cjmin. Fig. I. Thermal analysis of phthalic acid. Weight * of sampfe
234 TABLE
1
EXERGY E, (k ca1:-mole) FOUND PH-I-HALIC ACID AND FOR THE REACi-ION: ACID = PHTHALAMC ACID t HZ0
ACTIVATION
PhthAic acid Phthalic acid-g.Iycine Phtha!ic acid-Dr-vatine Phthzdic acid-rx-&mine PhthaIic acid-r_-phenykdmine
FOR THE DEHYDRATION PHTHALIC ACIDtAMINO-
OF
E.
Linear correlafion
29.2 32.1 26.4 41-g 36-S
0.999 0.999 0.998 O-999 O-998
Aminoacid Thermal analysis curves of glycine, DL-valine, DL-alanine and r_-phenylalanine give evidence that these aminoacids do not decompose respectively under 220, 275, 200 and 220°C. N-phthai)kminoacids The first thermal transformation for N-phthalyl-glycine, N-phthalyl-DL-valine, N-phthaIyl-DL-alanine and N-phthalyl-L-phenylalanine was the meIting observed respectively at 195, 1I 1, 162 and lS4’C; they all begin to decompose, with weight Ioss, respectively at 200, 160, 184 and 212X. Thermal condensalions The shape of TG and DTG curves (Figs. 2-5) indicates that all the aminoacidphthalic acid mixtures begin to react between 120-14O’C namely at a lower temperature than that required to convert phthalic acid into phthalic anhydride and to decompose the aminoacids. In any case the weight loss, amounting on the whole to two moles water, at low heating rates, occurs in two steps; the first one corresponds to 0.4-O-7 moies. Therefore the thermal condensation involves two consecutive reactions which became simultaneous when the first one rises the 4O-70%. The slope variation of TG curves at the first step indicates an induction period preceding the beginning of the second reaction. All attempts to separate compIeteIy the two reactions were useless even in isothermal conditions at the starting temperature of the first reactions. DTA curves deviate from the base line in the same temperature range of DTG ~curvesand afford always a singIe peak due to the sum of the enthalpic effects of the two reactions and of the melting of the reaction mixture. This last was observed with the aid of a Kofler hot stage microscope. All investigated systems, after Ioss of fwo moles of water, give thermal condensation products whose m-p- and infrared spectra are the same as that obtained with the relative X-phthaIyl-aminoacids prepared as test materials. To calculate the activation ener_g;y of the fu-st reaction Piloyan et aZ.‘s’ 3 equation was applied to DTG data; the obtained values are reported in Table 1. _(
235
i 140
I
I
150 Tempercttire
I
PC)
Fig. 2. Thermal behaviour of the system ture = 26.0 mg; heating rate = 1 ‘C/min.
I
:QO
phthalic
acid-glycine
(1-I).
Weight
of reactant
mix.
236
!
f
DTG ___-_ ____ -- __-__ -----_
; -.
.__--__-----______
- i
‘.
-.
_’
..!
ns ‘-‘!!
1
-_
,*. I
:r ,: i:
/ .’ i
;i ; g::
;
1-j i-cg/mir; i
D-!-A __-___-_______
r3U
Tenqeratwe
PC?
Fig. 3. Thermal bchavioui of the system Rure = 146.1 mg; heating race = 1 ‘C!‘min.
phthalic
acid-Ix_-vaiine
([:I)_
Weight
of reactant
mix
237
1
TG
!
I
! / :\,\-
!
+mg
i
i 1 i
\ \
i__E____ -. I -.
t
/
i
--a-
.-a,
\
\
% : . .
/”
\ %_,
\!
=;,‘\
.-
_ _- ------_
_____
-----
__
1
I
1 mc/min
+
I I
-l I‘_-m-_-m__ XA \*,< _------_________ _. *. . _#’ .. ; ,’ ;. i I .I 4 / ,I . 1 ;. , I i oJ$i I . r, % \ , . I 1 ,, I i .-\ _; * i ‘.* 1
Fig_ 4. Thermal behaviour of the system phthalic acid-Dr-alanine ture = 172-4 mg; heating rate = 1 “C;min.
(]:I)_
Weight of reactant mix-
238
‘i \ : !
_-
c-
_---------__________
.. :.
I
13c!
I
_I
150 Temperatw-e
(“C>
170
Fig- 5. Thermal khaviour of the system phthalic acid-r-phenylalaninc mixture = 138.0 mg; heating rate = I “C/min.
(I:l).
Weight of reactant
239
The therm31 behaviour of the investigated x-aminoacid-phthalic acid systems excludes the formation of phthalic anhydride and the successive condensation of this with the aminoacid; it can be explained admittin, 0 the formation of intermediate phthalamic acid foIlowed by the ring cIosure into X-phthalyl-aminoacid:
Over and above the first mechanism shouId require the activation energy of the first reaction to be independent of the nature of the aminoacid and equa1 to that of the formation of phthalic anhydride from the dehydration of phthalic acid. The different activation energy vaIues we have found (see Table 1) indicate the second mechanism to be the correct one_ ACKlr;OWLEDGEMEXi-
The financial support gratefully acknowIedged.
of this work by the Consiglio
Nazionale
delle Ricerche is
REFERENCES 1 D. A. Kidd and F. E. King, Xurure, I62 (1945) 776. 2 J. C. Sheehan and V_ S_ Frank, J. Amer. Chenr. Sac., 71 (1949) 15%. 3 L. Reese. Ann.. 242 (I 987) I_ 4 %I_ Fling, F. N. hlinard and S. W. Fox, J. Amer. Chem. Sac., 69 (1947) 2466. 5 J_ H. Billman and W. F. Harting, I_ Amer. Chem. SOL, 70 (1948) 1473. 6 J. C. SheeSan, D. W. Chapman and R. W. Roth, J_ Amer. Chem. SOL, 34 (1952) 3S22. 7 R. S. Tipson. J. Org. Chem., 21 (1956) 1353. 8 J. C. Sheehan, M. Goodman and G. P. &ss. 1. Amer. Chem. SOL, 75 (1956) 13679 G. Wanag and A. Veinbergs. Chem. Ber., 7.5 (1942) 1558. 10 J. J. O’Neill. F. P_ Veitch and T. Wagner-Jauregg, J_ Org. Ckem., 21 (19%) 36_111 F. E King and D. A. Kidd, 1. Chcm. Sac., (1949) 3315 12 K. BalenoviC, B. Gaspert and N. Stimac, Croat. C,lem. Acta, 29 (1957) 93. 13 G. 0. Piioyan, I_ D_ Ryabchikov and 0. S. Novikova, .Vaiure, 214 (1966) 1229.