Methylamine Recipe

METHYLAMINE

HYDROCHLORIDE

347

alcoholwas the principal product. Severai methods proposed for the dehydrationof diacetone alcohol were investigated. That of Hibbert2 (usinga very small quantity of iodine) is superior to the action of eitherconcentratedsulfuric acid or aiuminum phosphate.

METHYLAMINE

HYDROCHLORIDE

---+CHsNH2.HCI+ HCOrH 2HCHO + I\TH4CI Submitted by C. S. Mrnvnl and R. L. JnNrrNs. Checked by J. B. CoNaNr and F. C. WHroo,p.N.

1 . P ro c e d u re Ix a 5-1. round-buttoned flask, fitted with a stopper holding a set for downward distillation and a thermometer which will condenser well into the liquid, are placed 4 kg. (3711 cc., 47-53 moles) of extend technicalformaldehyde (35-40 per cent; sp. gr. 1.078 at 20") (see Notel" on p. 378) and 2 kS. (37 moles) of technical ammoniurn chloride.The mixture is heated on the steam bath until no more disiillate comesover and then over a flame until the temperature of the solutionreaches104o. The temperature is held at this point until no more distillatecomesover (four to six hours). The distillate, which consistsof methylal, methyl formate, and water, may be treated as describedin Note 1. The contents of the reaction flask are cooled to room temperature (Note2), and the ammonium chloride rvhich separatesis filtered off andcentrifuged(Notc 3). Tire mother liquor is concentratedon the steambath under reduced pre,ssureto 2500 -cc., and again cooled to roomtemperature,rvhereupon a second crop of ammonium chloride is obtained.The total rccover)r of ammonium chloride up to this point amountsto 780-815 g. The mother liquor is again concentrated under reduced pressure begin to form on the surface of the solution (1400-1500 q!,td.c,rystals cc.). It is then cooledto room temperature, and a first crop of methylaminehydrochloride, containing some ammonium chloride, is obtainedby filtering the cold solution and centrifuging the crystals (Note3). At this point 625-660 g. of crude product is obtained. The motherliquor is now concentrated under reduced pressure to about 1000cc.and cooled;a seconderop of methylamine hydrochloride (170190g.) is then filtered off and centrifuged. This crop of crystals is washedwith 250 cc. of cold chloroform, filtered, and centrifuged, in orderto remove most of the dimethylamine hydrochloride which is

348

ORGANIC SYNTHESES

present; after the washing with chloroform the product weighs 140150 g. The original mother iiquor is then evaporated under reduced pressure, as far as possible, by heating on a steam bath, and the thick sirulry solution (about 350 cc.) which remains is poured into a beaker and allowed to cool, with occasionalstirring, in order to prevent the formation of a solid cake (Note 2). The thick paste so obtained is centrifuged, and the crystals (170*190 g.) are washed with 250 cc. of cold chloroform; the solution is filtered and tlie crystais are centrifuged, thus yielcling 55-65 g. of procluct. There is no advantage in further concentratingthe mother liquor. The total yicld of crude eentrifuged methylamine hydroeliloride is 830-850 g. This procluct contains, as impurities, water, ammonium chloride, and some dimethylamine hydrochloride. In orcier to obtain a pure product, the crude methylamine h.vdrochlorideis recrystallizecl f r om ab-.o i u tea l c o h o l (N o te 4 ). T h e erucl esal t i s pl aced i n a 5-1. round-bottomed flask fitted rvith a reflux condenserprotected at the top u'ith a calcium chloride tube; 2 l. of.absoh-rtealcohol is added and t he m ix t u rc h e a tc d to b o i l i n g . Afte r about one-hal f hour the undi ssolveclmaterial is allowed to settle and the clear solution is pourcd off. \Vhen the alcohoiic solution is coolcd,rneth-vlaminehydrochloridc crystallizes out. It is filtered off and centrifuged,and the alcohol used for anothcr extraction. The processis repcated until the alcohol dissolves no m or e o f th e p ro d u c t (a b o u t fi r' e c x tracti onsare necessary). In the flask 100-150 g. of ammonium chloriclelernains, making the total recovery of ammonium chloride 850-950 g. The -vield of recrystallized methylamine hyclrochloricieis 600-750 g. (-15-5i per cetrt of the theoretical amount, based on the ammonium chlolide used up in tlie proces s ) ( Note s 5 a n d 6 ). 2 . N o te s 1. Methylal ancl soclium formatc may be obtained from the first distillate of thc main reaction mixture. The crude distillate is placed in a flask fitted u'ith a rcflux condenser,and to it is acldeda solution of 200 g. of sodium hyclroxiclein 300 cc. of water. The methyl formate is hydrolyzeclto socliumformatc. Thc rnethl'lal la1'eris -*eparated,dried over calcir"rmchloride, ancl distilled. In this rvay 240-260 g. of methylal, boiling at 37-42", is obtained. By evaporating the watery portion to dryness, a residue of about 280 g. of crude sodium forrnate is obt ained. e uti onssl i oul d be cool edrap2. T he m e th v l a m i n c h v c l ro c h l o ri clsol

METHYLI

idly in order to bring the easily purified. 3. Centrifuging the pre drying, as all the produc stand in the air. 4. Since ammonium cli cent ethyl alcohol (100 g hydrochloride purified in traces of it. A purer prod n-butyl alcohol, in rvhicht the boiling temperatureis ride is somewhat lesssolu as a rule three extraction fresh butyl alcohol for ea plete separation. Sincetl removed by exposureto a in a small quantity of wa and allowed to crystallize An entirely different n drochloride free of amm based on the fact that wlr reacts with an insufficien mine is preferentially neu 5. The literature2 cla amounting to 79 per cent r in the reaction. This figu methylamine hydrochlorid 6. Methylamine can which is distilled ancl tht acid.3 This method has I of the editors. 3.M

Methylaminc can be P iodide,a methyl chloride

l Sharp and Solomon, J. C 2 Werner. J. Chem. Soc. 1l 3 Sommelet, Compt. rend. ^ a Hofmann, Ann. 79, 16 (1 - 5 Vincent and Chappuis, B * 6 Ephrian and Gurewitsch, Soc. 1t7, ZJ6 (1920).

METHYLAMINE

HYDROCHLORIDE

349

idlyin order to bring the salt down in small crystals which may be purified. easily 3. Centrifugingthe precipitates is the only satisfactory method of drying,as all the products tend to take up water when aliowed to standin the air. 4. Sinceammonium chloride is not absolutely insoluble in 100 per ceniethyl alcohol (100 g. dissolve 0.6 g. at 15o), the methylamine purifiecl in the manner described contains apprcciable hydrochloride traces of it. A purer product can be prepared by recrystallizing from n-butylalcohol,in which the solubility of ammonium chloricleeven at theboilingtemperatureis negligibly small. Methylamine hydrochlorideis somewhatless soluble in this solvent than in ethyi alcohol, but asa rule three extractions carried out at 90-100" r,r'ith 4-6 parts of freshbuiyl alcohol for each extraction result in a substantially completeseparation.Since the last traces of the solvent are not rcadily removed by exposureto air, a solution of the rccrystallizeclrnaterial in a smallquantity of water should be distilled until free of alcoliol, andallowedto crystallize. An entirelydifferent method for preparing pure methylamine hyfree of ammonium chloride has been described.l It is drochloride based on the fact that when a mixture of methylamine and ammonia with an insufficientquantity of hvclrochloricacid the methylareacts mineis preferentially neutralized and the ammonia left free. 5. The literature2 claims a yield of methylamine hydrochloride to 79 per cent of the wcight of ammonium chloride used up amounting in thereaction. This figure is probably based on the weight of crucle hydrochlorideand not of the recrystallized material. methylamine 6. I\{ethylaminecan be purified through its benzal derivative, whiehis distilled and then hydrolyzed by concentratedhydrochloric scid.3This method has been checked ancl found satisfactorv bv one of ihe editors. 3. Methods of Preparation Methylaminecan be prepared by the action of ammonia on methvl methyl chloride,5dimethyl sulfate,6 methyl p-toluenesulfoiodide,a lSharpand Solomon,J. Chem. Soc. 1477(1931). 2 W e r n eJr ., C h e m .S o c .1 1 1 ,8 5 0 ( 1 9 1 7 ) . sSommelet, Compt. rend. 178, 2I7 (1924). . aHofmann, Ann. 79, 16 (1851). - sVincent and Chappuis,Bull. soc.chim. 45, 499 (1886). - 6Ephrianand Curewitsch,Ber. 43, 139 (1910); Denham and Knapp, J. Chem. Soc.117,236 (1920).

350

ORGANIC SYNTHESES

nate7 and methyl alcohol with a catalyst and at elevatedtemperatures;8 by the action of bromine and alkalie and of bleachingpowderl0 on acetamide; by the action of sodamide on methyl iodide;tt by the reduction of chloropicrin,l2 hydrocyanic or ferrocyanic acid,ls hexamethylenetetramine,lanitromethane,ls methyl nitrite,l6 or formalcloxime;1? from acetyl chloride and sodium azide;18and by the action of formalclehycieon ammonium chloricle.le TRodionov, Bull. soc.chim. (4) 45, 109 (1929).

8 D'vis and Elderfield,J. A.r. Ch.m. Soc. 50, 1286(1929); E. I. du Pont de N e m o u r sa n d C o . ,U . S . p a t . 2 , 0 1 7 . 0 5t C 1 . A.29,8001(tgBS)1. e Hofmann, Ber. 15, 765 (1882); Frangois,Compt. rend. 147, 430, 680, gg3 (1908). loBader and Nightingale,u*. S. prt. 1,489,480 iC. A. 18, 1g36(IgZ4)1. l l C h a b l a y , C o m p t . r e n d . 1 5 6 , 3 2 8( 1 9 1 3 ) . 1 2 G e i s s eA,n n . 1 0 9 , 2 S 2( 1 8 5 9 ) ;\ \ r a l l a c ha n d B o c h r i n g e r , A n n . 1 8 4 ,5 l ( l g Z T ) ; Frankland, Challenger,ancl Nicholls, J. Chcm. Soc. 115, l5g (1919). l s M e n d i u s ,A n n . l 2 l , 1 3 9 ( 1 8 6 2 ) ; D e b u s ,A n n . 1 2 8 , 2 0 1 ( 1 9 6 8 ) ; D e n h a m .Z . p h y s i k .C h e m . 7 2 , 6 7 4 ( 1 9 1 0 ) ;R i e d e l ,G e r . p a t . Z 6 q , S 2t8F r d l . 1 1 , 1 1 0 ( 1 9 1 2 - t a ) l ; Dreyfus,U. S. pat. 2,072.217 fC. A. 31, 2619(1937)1. laMeister, Lucius,and Briining, Ger. pat.78,812 tFrdl.3, lb (lgg0-4)l; Trillat and Fayollat, Bull. soc.chint. (3) 11, 23 (1894);Iiuntlsen,Ger. pat. 74B,lgZiFrcll. 7,24 (l9VLa)l; Mcisfsl, Lucius, and Briining, Ger. pat. 148,054tFrdl. 7,26 (190U)J; Isono,J. Pharm. Soc.Japan No. 397,209 (1915)tC. A. g,22BZ (1915)1. 15Pierron, Bull. soc. chirn. (3) zt, ZSB (lg9g) Mailhe and Murat, ibid. (4) ; 7,954 (1910); Zerewitinovand Ostromisslensky, Ber. 44,2402 (1911). 1 6 G a u d i o nB, u l l . s o c .c h i m . ( 4 ) 7 , 8 2 4 ( 1 9 1 0 )a n d A n n . c h i m .p h y s . ( g ) 2 5 , 1 3 6 (1912). 17Takaki and Ueda, J. Pharm. Soc. Japan SB, 226 (1998) tC. A. 32, EgZ6 ( 1 e 3 8l). 18Naegeli, Griintuch and Lendorff, Helv. chim. Acta lz, 222 (rg2g). l s B r o c h e t a n d C a m b i e r ,B r . r l l s. o c .c h i m . ( 3 ) 1 3 , 5 8 4 ( 1 8 9 5 ) ; F r a n g o i sC , ompt. r e n d .1 4 7 , 4 2 9( 1 9 0 8 ) ;W e r n e r ,J . C h e m .S o c .1 1 1 , 8 4 8( l g l 7 ) ; J o n e sa n d \ V h e a t l e y , J . A m . c h e m . s o c . 4 0 , 1 4 1 1( 1 9 1 8 ) ;\ \ z i e t z e al n d r ( o h l e r ,G c r . p a t . 4 6 8 , g g st c . A . 23,846(1929)1.

ME

METI

cHscocHCozczHs

I

(cH2)3cH3

2CHTCOOHCOzNa* Hz

I

(CH')'CH'

Subm Check

Ix a 12-1.round-bot stirrer, is pl:iceii 5 l. of a moles). To this is add 925 g. ) obt ained ( p. 2a8) fure is stirred at room t the monosubstituted ac passesinto solution. T, unsaponifiedrnaterialse ous layer is separateclI with a stopper fitted wir tube leading to a conde Through the separa cent ( sp. gr . 1. 40) sulf u than the amount requir in the saponificationof oxicle ceasesto be vigor boiling, and from onetilled. The clistillate is (N ote 2) and r edist ille In the distillate the l the latter is distilled un layer in this distillate ri tilled. This procedureir of ketone is obtainedin fraction is washed four trated solution of calciu * Commercially availabl