Kinetics & Mechanism of Reactions of Amides with Formaldehyde

Indian Journal of Chemistry Vol. 23A, February 1984, pp. 159-161

Kinetics & Mechanism of Reactions of Benzamide (B) (BDH, AR) was recrystallised from Amides with Formaldehyde ethanol, m.p. 130°. Monomethylolbenzamide(MMB), 0 m.p. 108-10 , and methylenebisbenzamide (MeBB), B RA VEENDRAN NAIR & JOSEPH FRANCIS*t m.p. 222-24° were also prepared by the method as Department of Applied Chemistry, University of Cochin, reported earlier". The structures of the compounds, Cochin 682022 viz. MMMeU, MeBPhU, MMA, MeBA, MMB and Received 30 May 1983; revised and accepted II October 1983 MeBB were compatible with their IR and PMR Kinetics of the reactions of substituted ureas like methylurea, spectra. . phenylurea, acetamide and benzamide with formaldehyde have been Kinetics of all reactions, except acetamide- studied, using a TLC method developed for the purpose. The formaldehyde reaction were followed by estimating increased reactivity of methyl urea towards formaldehyde. as the unreacted formaldehyde alone by the sulphite compared to urea, is due to the electron-releasing nature of the method 2 and sum of the free formaldehyde and methyl group. The reduced reactivity of phenyl urea is due to the electron-withdrawing nature of the phenyl group. The reduced methylols by the iodimetric method. In the reaction of reactivity observed in the case of acetamide and benzamide is also acetamide with formaldehyde, the free formaldehyde explained. was estimated by the hydroxylamine hydrochloride method:' since in the sulphite method large amount of The kinetics of reactions leading to the formation of sodium hydroxide, liberated when free formaldehyde methylolurea and methyleneureas in urea- reacted with sodium sulphite solution, hydrolysed the formaldehyde reaction have been recently in- acetamide and its compounds to acetic acid. Due to the vestigated 1 using a quantitative TLC method 2. Similar poor solubility ofbenzamide, methylenebis?enzamide, studies have now been carried out on the reactions of phenylurea and methylenebisphenylurea III water, a substituted ureas, like rnethylurea, phenylurea, mixture of water and 1, 4-dioxane was used as the acetamide and benzamide with formaldehyde, with a solvent. view to elucidating the effect of substituents on the Quantitative analysis of the reaction products of course of the reaction. acetamide and benzamide with formaldehyde was Formalin (38'>0' BDH, AR), containing less than 2~~ carried out using quantitative TLC 1. In the case of methanol was used. Methylurea (MeU) (BDH, AR) methylurea and phenylurea the reaction products was recrystallised from water, m.p. 102. Mono- were estimated as follows: The reaction was arrested methylolmethylurea (MMMeU) was prepared as and the unreacted formaldehyde destroyed with follows: aq. sodium bisulphite as reported earlier". A A mixture of methyl urea (7.4 g) and formaldehyde (8 portion (20/11) of the resulting reaction mixture was ml) was stirred along with potassium carbonate to spotted on a silica gel G plate, dried at room bring the pH to 9. The reaction mixture was kept at temperature and developed in suitable solvents. room temperature for 2 hr and for 48 hr at O'. The Methylurea and monomethylolmethylurea were crystals of MMMeU formed were decanted from ~he separated using I-butanol and phenylurea, viscous liquid and recrystallised from ethanol twice, monomethylolphenylurea and methylenebisphenyl- m.p. 122-25'. urea were separated using ethyl acetate as eluting Phenylurea (PhU) (BDH, AR) was recrystallised solvent. The plates were dried for 15 min at room from ethanol, m.p. 147°. Methylenebisphenylurea temperature and spots developed by spraying with (MeBPhU) was prepared as follows: A solution of phenylhydrazine sulphate-ferric chloride". The. spots phenylurea (13.6 g) in I,4-dioxane (IOOml) was stirred were removed and estimated colorimetrically by the with formaldehyde (4ml) and hydrochloric acid diacetylmonoxime method 1 using a Systronics 103 (0.5 mI). After 30 min, MeBPhU separated out as a spectrocolorimeter. The accuracy of the method was white solid which was filtered, washed with water and ±2%. recrystallised from 1, 4-dioxane, m.p. 8F. The main reaction steps involved in the present Acetamide (A) (BDH, AR) was recrystallised from investigation are given by Eqs (I) and (2) water, m.p. 81°. Monomethylolacetamide (MMA), m.p. 510, and methylenebisacetamide (MeBA), m.p. 2 Cl!.,:O R -NHCONH ~ RNHCONHCH 20H 199-201 ° were prepared as reported earlier". I

tPresent address: Head, Department of Polymer Science & 1+RNHCONH2~RNHCONHCH2NHCONHR Rubber Technology, University ofCochin, Cochin 682022 ... (1)

159 INDIAN J. CHEM., VOL 23A, FEBRUARY 1984

Table I-Second Order Rate Constants (k), Activation Energy (E) and Relative Reactivity Ratios for Various Amide- Formaldehyde Reactions at Various pH Values

[Amide] =0.25 moldrn -3; [formaldehyde] =0.25 moldm -3

Amide pH k x 104 dm3rnol-ls -I at E. Relative+ ------Umol-I reactivi- 20 30 40 50 60 65°C ty ratio Ul 2.5 7.15 I U1 3.5 19.55 I UZ• 4.7 0.93 I UZ 7.0 1.13 I UZ 9.0 15.95 I MU 2.5 13.54 3.8 MU 7.0 5.21 9.2 MU 9.0 11.34 23.64 51.29 61.09 3.0 AA 1.2 1.73 AA 2.0 0.084 0.17 0.38 64.43 AA 3.5 0.04 0.004 BA 3.5 0.272 0.86 1.95 83.68 0.245 BA 4.0 1.77 PhU· 3.0 0.324 0.62 1.72 57.32 PhU* 3.7 0.14 0.3 *First order rate constants (s -I). tReactivity of one primary amine nitrogen in urea is taken as unity.

slow PhU PhU + F~MMPhUr--MeBPhU ... (5) RCONH2 RCONHCHzOH last II Since the reaction of phenylurea with formaldehyde II+RCONH -+RCONHCH NHCOR ... (2) 2 2 directly results in the formation of MeBPhU, a direct (R= -CH3 or -C6HS) comparison of the rate constants with those of urea or The rate constants and activation energy values are methyl urea cannot be made. But first order rate summarised in Table 1. The methyl substituent in urea constants calculated for the disappearance of increases the rate of reaction with formaldehyde ten formaldehyde show that reactivity of phenylurea times atpH 7and four times atpH 2.5 at 30°. But under towards formaldehyde is only approximately 0.3 times alkaline condition (PH = 9)at 30 , the increase is nearly that of urea. This reduced reactivity of phenylurea is 26 times. The increased reactivity of methylurea due to the electron-withdrawing nature of the phenyl towards formaldehyde, as compared to urea, can be group. attributed to the electron-releasing nature of the When one of the amino groups in urea is replaced by methyl group. The lower rate under acid pH in - CH 3group (as in acetamide) and by - C6H 5 group comparison to alkaline pH may be due to the fact that (as in benzamide) the rate of reaction of the respective (i) the free base concentration is reduced by amide is reduced considerably. For acetamide the rate protonation in acid pH (Eq. 3), decreases to 1/400th of that of urea atpH 3.5 and 60'C. CH3NHCONHz+H+~H3NHCONH; ... (3) But for the benzamide the rate decreases to 1/8th of that of urea under the same conditions. and (ii) in alkaline pH the electron-releasing CH 3 IR and PMR spectra of the amides indicate that the group facilitates the formation of the anion (Eq. 4) amides are resonance hybrids and the C - N bond has CH3NHCONH2 +OH~H3NHCONH + H20 .. (4) a partial double bond character". These are feebly and hence the rate of addition of formaldehyde is basic and combine with acids (protons) to form salts. increased. PMR studies show that the salt of acetamide is In the reaction between phenylurea and for- protonated on the oxygen atom. This would be in maldehyde, MMPhU was obtained only in traces and agreement with the fact that amides are resonance from the beginning MeBPhU was obtained as the hybrids, the oxygen carrying a negative charge and the major product. This shows that the rate of nitrogen a positive charge. In acetamide the amino condensation of the MMPhU with free urea is faster group is deactivated since nitrogen is positively than its formation. The reaction can be represented as charged and oxygen negatively charged. In addition, in given in Eq.(5) acid medium the oxygen of acetamide is protonated

160 NOTES and nitrogen is permanently becoming positive even reaction. Therefore, the rate of its reaction with though - CH 3 group is slightly electron-donating. formaldehyde is not much reduced as compared to Hence the attack by the methylol carbonium ion at the urea-formaldehyde reaction. Small decrease in rate amino group is inhibited and the rate of the reaction is may also be explained as due to mild inductive effect of much reduced. In benzamide the amino group is benzene ring. deactivated to a lesser extent as compared to acetamide, since the strongly electron-attracting References carbonyl group which is in conjugation with the I Raveendran Nair B & Francis D J, J Chrom, 195 (\980) 158. benzene ring causes electron displacement away from 2 Raveendran Nair B & Francis D J, Polymer (London), 24 (1983) the nucleus and towards the carbonyl group (- R 626. 3 Nayar M R G & Francis 0 J, Makromol Chem, 179(1978) 1783. effect). In acid medium the negatively charged oxygen 4 Finar I L, Organic chemistry, Vol. I (Longrnans Green, London), will be protonated and amino group will be free for 1975,263.

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