844 WERNER METHYLATION BY MEANS OF LXXI1.--Methylation by Means of Formaldehyde. Part I. The Mechanism of the Interaction of Formaldehyde and Ammonium Chloride ; The Preparation of Methylamine and of Dimethyl-amine. By EMIL ALPHONSE WERNER. THE preparation of methylamine from formaldehyde and ammonium chloride is perhaps not so well known as it certainly deserves to be. Having occasion to make use of this reaction from time to time during the last few years the author has studied this interesting and important change the mechanism of which it must be admitted has up to the present remained decidedly obscure. Several new facts have been brought to light which have greatly helped to disclose what is now believed t o be the true mechanism of the progressive changes involved in this rather complex reaction.The interaction of formaldehyde and ammonium chloride was first examined by Plochl (Bey. 1888 21 2117) who from a rather superficial study of the cha.nge observed the formation of tri-methylamine and the evolution of carbon dioxide. No attempt was made to give an explanation of the reaction whereby the amine was produced. Some years later Brochet and Cambier (Cornpt. rend. 1895, 120 449 557; Bull. SOC. chim. 1895 [iii] 13 392) reinvestigated this reaction and showed what were the best conditions f o r the economic preparation of methyinmine hydrochloride by its means. The explanation which they have given of what they considered to be the main reaction is far from satisfactory and they have been decidedly at fault in their observations concerning certain experimental facts connected with the reaction.As a result of their investigations they have drawn the con-clusion that whilst methylamine is almost the sole ,product when ammonium chloride is used in excess trimethylamine is the main product when formaldehyde is in excess. The latter conclusion has not been confirmed. These investigators have evidently mistaken impure dimethyl-amine hydrochloride for the salt of the tertiary base only a small quantity of which has been detected when formaldehyde was used in excess and even then only when a relatively high temperature was attained. As regards their explanation of the reaction Brochet and Cambier have drawn the conclusion that " formaldehyde condense FORMALDEEYDE.PART I. 845 with ammonium chloride in a very complex manner ” ; it has been assumed that trimethylenetriamine hydrochloride (C‘H,:NR,HCl),, is a t once formed as a result probably of the polymerisation of methyleneimine CH,:NH produced in the first instance ; the polymeride then condenses further with formaldehyde whether the latter is present in excess or not to give methylamine hydro-chloride according to the equation 2(CH2:NH,HC1) + 3CH,O + 3H20 = 6CH,*NH2,HC1 + 3COp When the aldehyde is present in large excess they state “on arrive finalement au chlorhydrate du trimethylanline par une serie de rQactions identiques,” that is the compound, (CH, N-CH,,HCl),, is formed which in its turn condenses with kormaldehyde to form carbon dioxide methylamine and trimethylamine.It must be admitted that the above equation still leaves the ques-tion of the origin of methylamine rather obscure let alone the case of t rimet hylamine. More recently Knudsen (Ber. 1914 47 2694) has re-examined this reaction and whilst he has forestalled the author in showing that dimethylamine was produced he has not added any aseful information towards the elucidation of the mechanism by which the amines take origin. Thus it has been assumed that dimethyl-amine and trimethylamine are produced from the decomposition of a complex not t o say doubtful dimethylpentamethylene-tetramine formed in the first instance as a result of the union of methylamine with excess of formaldehyde. I n both cases then obscure condensation reactions have been regarded as explaining the formation of all three amines.This, i t will be shown is quite unnecessary in order to explain the different changes and moreover such a view is in contradiction to the observed facts. Mechanism of the Formation of Methylamiiie and of Dimethylamine. When a solution of ammonium chloride and formaldehyde (com-mercial formalin) in the proportions recommended by Brochet and Cambier was gradually heated a volakile liquid began to distil a t 50°; after heating a t 104O until distillation had prac-tically ceased the amount of distillate obtained was equal to 22 per cent. of the weight of the formaldehyde solut’ion taken. This distillate has been considered by Brochet and Cambier t o consist of methylal and water only; thus-they state that the pro-duct may contain from 60-79 per cent.of the former. Whilst methylal formed a considerable portion of the distillate 846 WERNER METHYLATION BY MEAN8 OF the chief constituent was methyl formate an important fact which Brochet and Cambier have completely overlooked. The composi-tion of thk distillate was fairly constant whether ammonium chloride or formaldehyde was present in an excess a t the outset. When methylamine hydrochloride and formaldehyde were heated in solution 90° was reached before distillation was observed ; the distillate contained methylal and methyl formate in nearly equal proportions; on the other hand from dimethyl-ammonium chloride and formaldehyde after heating under similar conditions a distillate was obtained which contained practically no methyl formate.The following results represenb the average composition of the distillates in the three respective cases : Percentage composition NH,CI + CH,O. of distillate. t = 104". Methyl formate.. .......... = 39.0 Methylal ..................... =34.6 Free formic acid ......... = 1.6 Water ........................ =24*8 CO freely evolved. (11.) NH,MeCl + CH,O. t = 104". 13.10 13.32 3.64 69-94 C02 freely evolved. (111.) N&Me,Cl+ CH,O. t = 110". 0.13 8.70 2-80 88.37 a traoe of CO evolved. Whilst the formation of methylal is a normal result of a reaction between formaldehyde and methyl alcohol (present in commercial formalin) promoted by hydrochloric acid set free during the process the production of methyl formate (and carbon dioxide) in considerable quantity furnishes an important clue to the mechanism of the reaction.The oxidation of formaldehyde to formic acid and. of the latter t o carbon dioxide must in the present circumstances be provoked by the presence of another substance having an equal tendency to undergo reduction. Through the decomposition of water the desired result is attained, a simultaneous oxidation and reduction is brought about and as a result of the latter methylamine and dimethylamine are pro-duced in accordance with the following scheme. The first phase of the change gives rise to methyleneimine, thus : (1) H-COH + NH,(HCl)* -+ H-CH<gEa I CH,:NH(HCl) + H,O It is the great tendency of formaldehyde to react with ammonia that no doubt determines a rapid dissociation of the haloid aalt; * When ammonium chloride and formaldehyde are mixed in solution, the liquid quickly becomes strongly acid from liberation of hydrogen chloride ; the brackets are used here to indicate the dissociated salt FORMALDEHYDE.PART I. 847 the feeble base CH,:NH remains largely dissociated since titra-tion using phenolphthalein as indicator shows all the hydro-chloric acid to be in the free state. Its presence however prevents polymerisation of the base and equilibrium (that is neutralisa-tion) is rapidly established by reduction and oxidation thus : (2) CH,:NH( HCI) + H,iO + H-COH = CH,*NH,,HCl + H*CO,H, and whilst part of the formic acid is neutralised by esterification, the larger portion is oxidised to carbon dioxide and water.As the temperature rises the main reaction (2) is soon accom-panied by a change similar to (l) in which methylammonium chloride takes part whereby dimethylammonium chloride is ultimately formed thus : (3) CH,O + NH2*CH,(HC1) = CH,:N*CH,(HCl) + H,O. (4) CH,:N*CH,(HCI) + H j0 + H*COH = (CH,),NH,HCl + H*CO,H. The next and final phase in the change is the result of a reaction between formaldehyde and dimethylammonium chloride thus : ( 5 ) CH,O + 2NH(CH3),(HCl) = C H 2 < ~ [ ~ $ 3 3 2 v ~ ~ ~ 0 + H,O. and since a stable saturated base is produced i t will show no tend-ency to suffer reduction and consequently there will be no oxida-tion of formaldehyde during this phase as shown by the results obtained under 111. I n accordance with this scheme theref ore trimethylamine cannot be directly formed during the progress of the changes which give rise to the primary and secondary bases and this explains why i t has not been detected in the relaction product when the temperature was not allowed to rise above say l l O o .If on the other hand the temperature be carried too high as was the case in Knudsen's experiments (Zoc. cit.). or the heating be unduly prolonged a condition which can scarcely be avoided in dealing with the final mother liquors after the separation of the bulk of the chlorides of methylamm~onium and of dimethylammon-ium then some trimethylamine is undoubtedly produced. The evidence goes t o show that the tertiary base very probably arises from the decomposition of the above methylene base thus : (6) CH,<N(CH3)2,2HCl = N(CH,),,ECI + CH,:N*CH,(HCI).N(CH,), The unsaturated base in the absence of excess of formaldehyde is polymerised to the compound (CH2:N*CH&,* the presence of which * This base has been prepared by Henry (Bull. Acad. TOY. Belg, 1893, [iii] 26,200) and later by Brochet and Cambier (Zoc. c i t . ) who determined its molecular weight 848 WERNER METHYLATION BY MEANS OF can be shown by the formation of a copious precipitate on addition of picric acid. The picrate (m. p. 1 2 7 O Duden and Scharff Ber., 1895 28 936) cannot be crystallised from water on account of the eaw with which it dissociates. Since the changes represenbd by equations (2) and (4) overlap during the progress of the reaction the production of dimethyl-ammonium chloride in moderate quantity cannot be avoided.Its separation from a considerable amount of methylammonium chloride is however a very simple matter as dewribed later on. By adopting such conditions as were indicated by the above scheme a very large yield of dimethylammonium chloride has been obtained with the use of much less formaldehyde than was found necessary by Knudsen (Zoc. cit.). The absence of condensation pro-ducts in the early stages of the reaction that is both before and after large quantities of methylammonium and dimethylammonium chlorides have been produced has been proved by the fact that no precipitation was produced on the addition of picric acid. This reagent forms sparingly soluble compounds with all the condensa-tion products or polymerides which have hitherto been supposed to play a past in the formation ,of the1 primary and secondary bases produced in this interesting and important reaction.Preliminary experiments have proved the wide scope of tlie use of formaldehyde for inethylating amino-compounds of various types, o n the lines of the scheme just recorded. These it is to be hoped, will be described in the near future. E x P E R I M E N T A L. The P r e p r a t i o n of Methylammoiiiuni Chloride. The proportions of ammonium chloride and formaldehyde (40 per cent. formalin) * recommended by Brochet and Cambier (Zoc. cit,), namely one part by weight of the1 former and two parts by weight of the latter were found after several trials to give the best results.Since about 35 per cent. of ammonium chloride has always been recovered unchanged the1 molecular ratios NH4C1 2CH,O required by theory are very closely represented by the above proportions. Expt. I.-Two hundred and fifty grams of ammonium chloride and 500 grams of formaldehyde solution were gradually heated in a distillation flask which carried a thermometer with the bulb well below the surface of the liquid. The temperature was slowly raised to 1 0 4 O and was not allowed to rise above this point a t which it * Analyses of seven different samples of commercial formalin gave as a mean result 35 per cent. of formaldehyde and in no case was a sample found to contain 40 per cent. The highest value was 37.4 per cent. the lowest 33-2 per cent FORMALDEHYDE.PART I. 849 was maintained until no more volatile liquid distilled ; this required about four and a-half hours. The distillate weighed 110 grams. The product was allowed t o cool and after filtration from 62 grams of ammonium chloride which had separated was concentrated by evaporation a t looo to about one-half of the original volume. After removal of 19 grams of ammonium chloride,* the liquid was again concentrated by evaporation until a crystalline Scum had formed on thel surface of the hot solution. After cooling 96 grams of methylammonium chloride (Found, C1= 52.46. Calc. C1= 52.59 per cent.) were separated; after further concentration a second crop (18 grams C1= 52.39 per cent.) was obtained. The filtrate was now concentrated as far as possible a t looo and was left for twenty-four hours in a vacuum oveir sodium hydroxide after which the semi-solid residue was digested with chloroform when 20 grams of methylammonium chloride (C1= 52.63 per cent.) which had been washed with chloroform to remove dimetliylammonium chloride were obtained.The total yield was 128 grams. From the chloroform solution after removal of much of the solvent by distillation 27.5 grams of dimetliylanimonium chloride1 were obtaine'd (Found C1= 44.38. Calc. C1= 43.5 per cent.). A visoous residue (76 grams) which did not crystallise after remaining for a week in a vacuum over sulphuric acid was finally obtained; it contained C1=40*37 pelr cent. It was distilled after the addition of an excess of a 40 per cent. solution of sodium hydr-oxide and the alkaline vapours evolved were absorbed in an alco-holic solution of hydrochloric acid when a small quantity of methyl-ammonium chloride and a relatively large quantity of dimethyl-ammonium chloride were! obtained but no trimethylammonium chloride could be detected.Formaldehyde was also regenerated by the action oi sodium hydroxide on the viscous material which no doubt contained much tetramethylmethylenedianiine hydrochloride, C13,(NMe2),,2HCl which requireis C1= 40.57 per cent. Examination of Volatile Liquid Distillate.-This had D15 0.927. Five C.C. after digestion with 50 C.C. of IV-dium hydroxide required 18.15 C.C. of N-sulpliuric acid f o r neutralisation. Five c.c. after removal of methyl formate and methylal by heat a t 70° left an acid liquid which required 1.65 C.C.of N-sodium hydroxide for neutralisation. Hence H*CO,Me = 39.09 ; CH,O = 1.62 per cent. The proportion of methylal was determined by differ-ence after removal of water by anhydrous calcium chloride. The * Ammonium chloride is very sparingly soluble in a concentrated solution of methylammonium chloride and consequently its separation from the latter salt is very sharp. L L 860 WERNER METHYLATION BY MEANS OF separation o i methyl formate from methylal by fractional distilla-tion was found t o be an extre8mely tedious process and was aban-doned as useless from an economic point of view. The value of the distillate is of iriiportance since all the formic acid can be easily recovered as sodium formate after shaking with a solution of sodium hydroxide in the cold and thus separated from methylal.The following results illustrate the value of the whole process from an economic point of view. From an experiment with 4000 grams of formalin and 2000 grams (of ammonium chloride and without working up the final viscous residue therei were obtained 1037 gram of pure methylammonium chlocride 218 grams of nearly pure dimethylammoniuin chloride 408 grams of anhydrous sodium formate and 264 grams of pure methylal (b. p. 42-43O) whilst 698 grams of ammonium chloride were recovered. The' yield of methylammonium chloride was equal to 79.6 per cent. of the weight of ammonium chloride which had entered into' reaction. When the value of the by-products is taken into consideration it will be seen that the methylammonium salt is obtained for a very small outlay.Pr epura ti o n of Dime thy la mmo 7 1 iu m C h lo ride. The formation oi the above salt in this reaction has been recently pointed out by Knudsen (Zoc. c i t . ) but the method adopted for its preparation distinctly shows the absence of a reasonable apprecia-tion of the probable mechanism of the changes. Thus in an experi-ment designed with the object of obtaining the best yield of the secondary amine a useless not to say a wasteful excess of form-aldehyde was employed without any particular advantage. The following experiment carried out on the lines of t.he present theory, gave a very good result. E'xpt. 11.-Two hundred grams of ammonium chloride and 400 grams of formalin were heated t o 104O as in Expt.I and 65 grams of ammonium chloride were recovered. To the filtrate 300 grams of formalin were now added and the solution was again heated at this stage to 1 1 5 O and maintained as nearly as possible a t this hi-p r a t u r e until no more liquid distilled. This required about three and a-half hours. Since methylammonium chloride produced during the first stage is less easily dissociated than ammonium chloride a higher temperature was required to bring about reac-tion (3). It was noticed that whilst a volatile liquid commenced to distil a t about 52O in the first stage 92O was reached in the second stage before any liquid distilled which is quite in agreement with theory. The product was concentrated by evaporation a t looo until a scum appeared on the surface of the hot liquid; 7 grams of ammon FORMALDEHYDE.PART I. 851 ium chloride and 27 grams of pure methylammonium chloride were recovered from the material which had separated after cooling. The product was now heated t o 120° until a portion when cooled became a semi-solid crystalline mass after which it was allowed t o remain for two days in a partial vacuum over sodium hydroxide. It was then treated with chloroform as described under Expt. I and 122 grams of nearly pure dimethylammonium chloride (Found, C1= 43.14. Calc. C1= 43.5 pel* cent.) were ultimately obtained. The final residue contained some trimethylammonium chloride but was not further dealt; with. The yield of dimethylammonium chloride calculated on $he weight of ammonium chloride which had entered into reaction (that is, 200-72=128 grams) was therefore 95.3 per cent.with the use of 700 grams of formaldehyde solution. Knudsen obtained a yield of 70 per cent. from 100 grams of ammonium chloride and 1000 grams of formalin. Production of Tm'methylaminoizium C'hloride from the Iuteraction of For maldeh yde and Di in e t lip lnm m o 11 i u ni C'?i lo ride. I n order to prove the origin of trimetliylamine in accordance with the present theory the following experiment was made. Expt. ZI1.-Dimethylammonium chloride (20.5 grams) and 45 grains of a solution of formaldehyde (molecular ratio 1 :2) were heated in a distillation flask t o l l O o f o r four hours. The composi-tion of the distillate which weighed 18 grams is given under I11 (p. 846).The product after concentration as far as possible by evaporation a t 100° was heated to 120° after which i t was allowed to remain over sodium hydroxide as in Expt. 11. The residue was dissolved in chloroform and on addition of ether (well dried) 4.5 grams of crystals were precipitated which contained C1= 36-93 (C,HgN,HC1 requires C1= 37.17 per cent.). A platinichloride was prepared which contained Pt = 37.03 (C,HgN,H2PtC1 requires Pt = 36.95 per cent.). The residue after removal of the solvent was distilled with a 40 per cent. pot,assium hydrotxide solution ; t h s alkaline distillate, which possessed a strong odour of formaldehyde was easily proved t o consist chiefly of dimethylamine with only a small proportion of the tertiary base. The original reactio'n product tetramethyl-methylenediamine hydrochloride was readily hydrolysed when heated with a solution of potassium hydroxide thus, CH2(NM%),,2HC1+ 2KOH = CH20 + ZNHMe + 2KC1+ H20.The small yield of trimethylamine was due to the relatively low temperature attained during the process. L L* 852 METHYLATION BY MEANS OF FORMALDEHYDE. PART I. E s p t . IV.-The above was repeated but t h e temperature was raised to 160° after evaporation a t looo; a yield of 14 grams of trimethylarnmonium chloride was obtained thus proving the 'origin of the tertiary base as shown in the' schemel equation (6). Bekaviour of :~~et~i'ylanzmoniz~m Chloride and Formaldehyde i n t h e Presence of Ethyl Alcohol. According to theory no inethylammonium chloride should result from the interaction of ammonium chloride and formaldehyde in the abmnce of water a point which is not suggested by such an equation as 2CH,O + NH = CH,*NH + H*CO,H which is given by Knudsen t o show the formation of methylamine.The insolubility of amnionium chloride in pure alcohol preseats a difficulty in the use of this salt; however the test has been made with the methyl derivative . Expt. V.-Seventeen grams of inethylammonium chloride and 15 grams of paraformaldehyde (2 niols.) were heated with 50 C.C. of alcohol under reflux. The aldehyde was rapidly depolymerised and a clear homogeneous solution was obtained as soon as the boil-ing point of aicohol was reached. After a short time the liquid gradually separated into two layers and the change was completed after one hour.The lower layer when cold was a semi-solid crystal-line mass from which 10.5 grams of methylammoniuni chloride were recovered. The supernatant liquid was shaken with a saturated aqueous solu-tion of calcium Chloride dried and distilled; 46 grams of ethylal (b. p. S8-SS0) were obtained which was equal to 88.4 per cent. of the theoretical from 15 grains of formaldehyde. When molecular proportions of methylammonium chloride (1 7 grams) and paraform-aldehyde (7.5 grams) were used 13.5 grams of the amine salt were recovered and 20 grams of ethylal were obtained. No dimethylammonium chloride was formed which bears out the part played by water in the general reaction. Ititeractign of Formaldehyde and Animonizcm Chloride in t h e Presence of W a t e r alone.It was pointed out in the results given under Ex@. I t h a t the yield of mehhylammonium chloride was equal to 79.6 per cent. of t h e weight of ammonium chloside which had entered into reaction. Theoretically from equations (I) and (2) one molecular proportion of ammonium chloride should yield one of methylammonium chloride t h a t is 126.1 parts of the latter salt from 100 parts of the former. With the use of commercial formalin there is inevitabl DRAKELEY LIBERATION OP HYDROGEN SULPHIDE ETC. 853 loss of formaldehyde as methylal which for obvious reasons cannot be profitably counteracted by using an exoess of the aldehyde solu-tion. This loss of aldehyde) is undoubtedly one of the factors t h a t affects the ultimate yield of methylamine; when it was eliminated bv the use of paraformaldehyde a larger yield of the amine was obtained.Expt. VZ.-Twenty-seven grams of ammonium chlo,ride 30 grams of paraformaldehyde (molecular ratio 1 :2) and 80 C.C. of water were gradually heated. A t SOo a clear solution was obtained and the temperature was maintained for four hours a t 1 0 4 O . Slightly more than one-third (9.06 grams) of the ammonium chloride was recovered whilst 18-96 grams of pure methylammonium chloride were obtained. This equals 105.6 parts from 100 parts of am-monium chloride. The amount af dimethylammonium chloride produced was not estimated. It is not suggested from the results of this experiment that paraforinaldehyde could be economically used on a large scale with advantagel since quite apart from its relatively high cost neither formic acid nor part of the unchanged aldethyde can be recovered as by-products. The experiment has served to support the views put forward and perhaps on a small scale may have some advantage. Many 9ther points dealing chiefly with the identification of the intermediate products which have not been touched upon in the present paper will be elaborated in a future communication. UNIVERSITY CHEMICAL LABORATORY, TRINITY COLLEGE DUBLIN. [Received July 3 lst 19 17.