A Novel Reaction of Primary Amines with Trichloroacetonitrile

A NOVEL REACTION OF PRIMARY AMINES WITH TRICHLOROACETONITRILE

John Constantin Grivas

A thesis submitted to the Faculty of Graduate Studies and Research of McGill University in partial fulfilment of the requirements for the degree of Master of Science

McGill University Montreal, Canada April 1957 AC~

The author gratefully acknowledges the guidance given by Dr. A. Taurins who directed this work. TABLE OF CONI'ENI'S

GENERAL IID'RODUCTION ••• • • • • • • • • • • • • • • • •••• 1 HISTORICAL INTRODUCTION • • • • • • • • • • • • • • • • • • • • 2 Amidines: Nomenclature and classification • • • • • • • • • 2 Preparations from nitriles and amines • • • • • • 3 The chemistry of trichloroacetonitrile • • • • • • • • • • 20 Reaction of P,Yridine with bromine • • • • • • • • • • • • • 24 Pyridine perbromides as brominating agents • • • • • • • • 27

DISCUSSION • • • • • • • • • • • • • • • • • • • • • • • • • • • 30 Reaction of primary amines with trichloroacetonitrile • • • 30 Aspects or the reaction mechanism • • • • • • • • • • • • • 36 E:trect or N-substituted trichloroacetamidines on the skin • • • • • • • • • • • • • • • • • • • • • • 43 Reaction of pyridine dibromide with aniline • • • • • • • • 44 Correlation between the infrared spectra and the structure of N-substituted trichloroacetamidines • • • • 47

EXPERIMENTAL • • • • • • • • • • • • • • • • • • • • • • • • • • 56 Preparations of: Ethyl trichloroacetate • • • • • • • • • • • • • • • • 56 2,2,2-Trichloroacetamide • • • • • • • • • • • • • • • 56 Trichloroacetonitrile • • • • • • • • • • • • • • • • 57 N-phenyltrichloroacetamidine • • • • • • • • • • • • • 57 N-phenyltrichloroacetamidine hydrochloride • • • • • • 5S N-methyltrichloroacetamine • • • • • • • • • • • • • • 5S N-methyltrichloroacetamidinium picrate • • • • • • • • 59 N-ethyltrichloroacetamidine • • • • • • • • • • • • • 59 N-ethyltrichloroacetamidine bydrochloride • • • • • • 60 N-benz.yltrichloroacetamidine • • • • • • • • • • • • • 61 Methylamine hydrochloride and trichloroacetonitrile • • • • • • • • • • • • • • • • • • • 62 Ethylamine hydrochloride and trichloroacetonitrile • • • • • • • • • • • • • • • • • • • 62 Reaction of trichloroacetonitrile and hydrazine • • • 63 Preparation of pyridine dibromide: In acetonitrile • • • • • • • • • • • • • • • • • • • 64 In carbon tetrachloride • • • • • • • • • • • • • • • 65 Reaction of p,yridine dibromide with aniline • • • • • • • • 65 TABLE OF CON'l'Em'S (ii)

Preparation of: 2,4,6-Tribromoacetanilide • • • • • • • • • • • • • • 67 2,4,6-Tribromobenzanilide • • • • • • • • • • • • • • 67 2,4,6-Tribromoformanilide • • • • • • • • • • • • • • 67

Infrared absorption spectra • • • • • • • • • • • • • • • • SUMMARY AND CON'l'RIBUTIONS TO Knll.EDGE • • • • • • • • • • • • •

BIBLIOGRAPHY • • • • • • • • • • • • • • • • • • • • • • • • • • 74 GENERAL INTRODUCTION

The addition of free amines to the nitrile group of trichloro acetonitrile CCl.3 C=N is not mentioned in any reviews or textboolœ summarizing the general chemical properties of nitriles. The reason for this is that this reaction bas not been described in any chemical jour nal. It has been mentioned only in the German Patent 671,785 (1939), which states that the reaction has been carried out under anhydrous conditions at low temperature. We round that trichloroacetonit!ile reacts with primary and secondary aliphatic, aromatic and heterocyclic amines at mild conditions without any catalysts, even in dilute solutions at room temperature. There are no side-products of reactions, and the products formed are of high purity and uniformity. The objective of the first phase of this research was to stuqy the preparation and characterization of N-substituted trichloro acetamidines by the interaction of several primary amines, on trichloro acetonitrile, and to record the infrared spectra of these synthetic products. There are plans to continue this work by extending the scope of reaction to various secondary and heterocyclic amines. Another angle of research will be the physical-organic stuqy of the kinetics of this reaction, and the kinetics of hydrolysis of the new N-substituted trichloroacetamidine~.

The other problem in this research was to stuqy the interaction of pyridine dibromide with aniline in acetonitrile solution. 2.

HISTORICAL

AMIDINES

Nomenclature and Classification Amidines are monoacid bases characterized by the formula (I) N-R' R" R-~-N/ (I) 'R,nt where R, R', Rtt, Rttt are hydrogen, al~l or ar,yl radicals and their substitution products. In general, an amidine is named after the acid or amide which may be obtained from it by hydrolysis, according to the system employed in the Chemical Abstracts; thus (II) is acetamidine.

(II)

The carbon atoms adjacent to the amidine carbon atom are designated in the same manner as those adjacent to a carbonyl group ( 0<, f1', 0 , d ... etc.); thus (III) is named 6?-phenylpropionamidine.

c H - CH -CH -C -NH (III) 6 5 2 2 Il 2 NH The nitrogen atoms of the imino and amino groups are not differ- entiated by this system and are referred to as N and N'.

If it is difficult to name the compound as a derivative of an acid, the amidine group is referred to as carboxamidine, e.g. (IV) is named stilbene-4,4'-dicarboxamidine. 3.

NH ~N-C" .CH =CH (IV)

Amidines may be classified into five general types according to the number and distribution of the substituents on the nitrogen atoms.

NH I. Unsubstituted R-C~ '~

II. Monosubstituted or

III. Symmetrical disubstituted ;NR' NHRt R-e or R-C.,? 'NHR'' ~NR'

~NH IV. Unsymmetrical disubstituted R-C~ 'NR'R'' v. Trisubstituted

The preparation of amidines from nitriles and amines Cornell (1) has prepared unsubstituted amidines in low yields by heating the corresponding nitriles with ammonium chloride in liquid ammonia in sealed tubes; he observed that no reaction occurs when only the nitrile and ammonia were used.

Bernthsen (2) by a similar procedure prepared many unsubstituted amidines in ver,y low yields.

Pinner (3,4) dèscribed the synthesis of unsubstituted amidines from nitriles via the imidic esters; the nitrile was dissolved or suspended in anhydrous alcohol and treated with an excess of dry hydrogen chloride forming an imidic ester hydrochloride (V), which was then caused to react with ammonia 1 as in the following scheme

.hNH R-C.:N + R'OH + HCl~R-C~ .HCl (V) OR'

~NH (V) + ~R-C .HCl + R'OH 'NH 2

AYdrogen bromide may be substituted for hydrogen chloride and alcohols other than ethanol may be used (3). The above method is general and mononitriles as well as dinitriles, aliphatic or aromatic, have been used (5). Thus Lamb and White (6) prep ared decanebis-(N-cyclohexylcarbonamidine) (VI) which cr,ystallized from acetone-alcohol mixture in needles, m.p. 122°.

(VIa)

VI Pinner (.3) and Gautier (7) obtained even formamidine hydro chloride (VII) from cyanogen. ..,..,oR H-C=:N + ROH + HCl- H-C 'NH•HCl

00 ~- -e/ NH H C ,----z H + .3~- 'ibo. .HCl + ROH ~NH.HCl ~NH

(VII) Functional groups which do not react with the reagents or the products do not alter the course of the reaction and hydrochloric acid seems to be necessary (8,9).

0 ==C-OC H 0 =C-OC H O=C-OC H 2 5 1 _.,.,_ 1 25 1 2 5 CH -C-NH c~.c= N c~- c=NH 2 1 1 OC H NH 2 5 2 There are limitations as to the type of the unsubstituted amidines which can be prepared by Pinnerts method. Acyl or benzoil cyanides cannot be used, as they give their esters with the evolution of hydrogen cyanide (.3).

HCl c H -c -C=N + ROH C6H5-C-OR + HC=N 6 5 Il - M 0 0 Ortho-substituted aromatic nitriles were unreactive with alcohols and hydrogen chloride, whereas their isomers formed imidic esters, converted to amidines; thus p-toluenenitrile (VIII) and 0-naphthlenenitrile (IX) were ...... found reactive, while 0-toluenenitrile (X), ~ -naphthalenenitrile (XI), 2-amino-4 methylbenzonitrile (XII) and 2-nitro-4 methylbenzonitrile (XII) 6. gave negative results.

VIII

IX : x

XI :

XII .

XIII

Steric hindrance plays an important role in these reactions, but the exact limitations are unknown; an example is the formation of o-alkoxybenzamidines (XVI) from o-alkoxybenzonitriles (XIV), (10)

XIV xv XV + NH OR 3 C=NH O 1 • HCl ~ XVI

The mechanism of this reaction is not known yet; nevertheless, Knorr (16) suggested that the following process involving an ammonium ion may be possible. .. .. ~ ,.NH NH NH '-Il Il R-C-ORt ~R-ë-OR :~ ~RC::.NH + ROH .,. R-J1 l +S @ffi3 :~

Monosubstituted amidines may be prepared from the salts of the al~l and aryl primary amines and nitriles under the influence of heat (11,12), but it has the disadvantage that disubstituted amidines are also formed as by-products. Thus, N-phenyl-phenylacetamidine (XVIII) was obtained by heating aniline hydrochloride with ben~l nitrile (XVII) at

220-240° in sealed tube for one day (13,14).

Starting with nitriles, via imidic esters, monosubstituted amidines may be produced by replacing the ammonia with primary amines (3,15). 8.

Hill and Rabinowitz (17) prepa.red some amidines of the "Halo caine" type using the same method, (a) by replacing the methyl groups of

Holocaine (XIX), which is regarded as an efficient local anaesthetic !or opthalmic purposes, with alkyl or aralkyl groups, and (b) by replacing one phenetidine group by the amino (XX) or dialkylamino groups (XXI)

XIX xx

XXI

An example is the preparation of the Holocaine itself by treating two molecular equivalents of p-phenetidine (XXII) in dry ether with a sus- pension of the imidic ester hydrochloride in the same solvent; the mixture was allowed to stand for 21 days at room temperature and occasionally shaken. The precipitate was filtered off, and the filtrate was placed under a bell jar in a vacuum in order to remove the ether. After solid- ification had occurred the crude material was purified by crystallization from 60% ethanol

....

XXII ~ N- c6H5 - OC2H5 CH.f C'\,. + NH4Cl + C2H50H NH- H - OC H c6 5 2 5

Another example is the synthesis of p-etho:x;yphenylacetamidine by treating an ether solution of the imino ether with one molecular equivalent of p-phenetidine in the same solvent. After 18 days of standing the precipitated solid was purified by crystallization from the same solvent.

- Salts of secondary aromatic amines and nitriles have been used for the synthesis of unsymmetrical disubstituted amidines in yields from twelve to thirty per cent; Bernthsen (2) has prepared N,N-diphenylbenz amidine (XXIII) by heating diphenylamine hydrochloride and benzonitrile. The mixture was then extracted with water and the amidine precipitated by the addition of ammonium hydroxide. 10.

XXIII

Pinner (18,19) extended his method for the preparation of symmetrica1 disubstituted amidines with the synthesis of the N,N'-di- methy1formamidine (XXIV) by heating ethy1 formidate hydrochloride (XXV) with an excess (1:3M) of methy1amine in a1coho1; after standing for sev- era1 daye the excess of methylamine was disti1led off by means of a water bath and the residue was crystallized from alcohol:

XXIV

Luckenbach (20) treating secondary amines with the hydrochloride of the imidic esters isolated the formed unsymmetrical substituted amidines in the for.m of salts; e.g. ethyl phenylacetimidate hydrochloride (XXVI) and an excess of dimethylamine in absolute ethanol gave N,dimethyl phenylacetamidine hydrochloride. (XXVII) which was converted to its salt with 11.

chloroplatinic acid.

XXVI XXVII

Oxley and Short (21) reported the preparation of amidines and their N-monosubstituted derivatives from ammonium or a~l- or aryl- ammonium salta of an aromatic or aliphatic sulphonic acid with a cyanide at a temperature wi~hin the range 180-300°; the cyanide and the salt of the sulphonic acid were heated with stirring and an homogeneous me1t was usually produced but, in a few cases, the mixture became homogeneous as the reaction proceeded; the amidine benzesulphonates in general are lesa soluble in cold water than the corresponding hydrochlorides and it was possible to extract the unchanged cyanide from the reaction product with ether or acetone and then separate the residual mixture of amidine and ammonium salta by crystallization from water or alcohol. Alternatively, the free amidine was liberated by the addition of ammonia or 5N sodium hydroxide to an alcoholic or aqueous solution of the salt. The aqueous solutions of the sulphonic acid salta or ammonia and amidines frequently dissolved considerable amounts of nitriles which are insoluble ~ water; the free bases were collected in a suitable solvent or by filtration and were separated from the unchanged nitriles by solution in hydrochloric acid. The ammonium salta of a variety of sulphonic acids were employed and in a number of cases the use of a salt of an alkanesulphonic acid was advantageous owing to the lower m.p. and the greater solubility of 12.

the cyanide in the melt. This method can be used in the preparation of monoamidines from dicyanides, is applicable to a naphthyl cyanide and o-substituted phenyl cyanides and it has the advantage that it is a one-stage process which· can be operated without employing a solvent. An example is the formation of

N,N-diphenylbenzamidine (XXVIIT) from a mixture of diphenylamine benzene sulphonate (XXIX) and phenyl cyanide in 29% yield.

e oso c H + c Hç C~N 2 6 5 6

XXIX

Na OH c H51=NH • HOS0 -c H -- 6 2 6 5 - /N\ C6H5 C6H5

XXVIII

They suggested that the additive capacity of the cyano-group may be enhanced by an "imported" stimulus and represented the mechanism as follows: -

R.C~~ }@ '\NHR" 13.

The same two workers found that the formation of amidines from phenyl cyanides was usually promoted by groups which act as electron-sinks (p-Br, p-N02) and retarded by those which act as electron-sources. Partridge and Short (22) prepared amidines and N-substituted amidines. in a modified method by heating cyanides with ammonium or alkyl-~ monium thiocyanate and found that the yields were sometimes higher than those obtained with ammonium .sulphonates. The yield increased with increase in the ratio of the ammonium thiocyanate to cyanide, the optimum quantity of the thiocyanate being ca. 4 mols., and decreased by small variation from the temperature and time of the reaction. The general procedure was as follows; the ammonium thiocyanate or substituted ammonium thiocyanate and the cyanide were heated and if the reactants were immiscible, the mixture was stirred vigorously and heating was continued for one hour after the two layers had coalesced. The product was dissolved in water, and the amidine was liberated with 5N- sodium hydroxide or, in the case of weakly basic amidines, with ammonia; it was then separated from the unchanged cyanide by solution in hydrochloric acid. The amidine was reprecipitated from the water solution of its salt by addition of 5N-sodium hydroxide or ammonia, washed with ice-water and dissolved in an equivalent of hydrochloric acid. The amidinium chlorides were obtained by concentrating the solutions by distillation under diminished pressure.

NH2 1 C=NH.HSCN + HOOC' -HOOC

xxx 14.

(XXX) or NaOH HOOC

XXXI

NH Il • HCl c·-NH2 (XXXI) + HCl

Hullin et al. (23) found that amidines are for.med by decomposition

of the complexes produced from ar,yl or alkyl cyanides and aminomagnesium

halides, NRR' .Mg. Hal, but whe n R and R' were hydrogen the yields were

very small and the reaction failed when bath were aryl groups. Thus

N,N-dibutylbenzamidine (XXXIII) was isolated in 80% yield by treating a mixture of secondary n-butylamine, ethylmagnesium bromide and pheeyl cyanide

and decomposition of the product with a solution of ammonium chloride

XXXII

(XXXII)

XXXIII 15.

Oxley, Short and Partridge (24) used catalysts like aluminum chloride, zinc chloride, ferric chloride and stannic chloride in the preparation of amidines which promote their formation by stimulating the additive capacity of the cyano group. They explained the action of such catalysts assuming that they might enhance the dipole condition of the nitrile by formation of alkyl cyanide-catalyst complexes and with it its reactivity.

@ e R- + C=N AlC13 R-1::.NH -+-AlC13 NR' 2

The complex of the amidine with the catalyst was carefully decomposed with water, and the amidine hydrochloride formed was precipitated and collected; when the salt was soluble in water the amidine liberated by excess of aqueous NaOH.

The same authors extended their reaction for the preparation of amidines from ammonium or alkyl- or aryl-ammonium salts of an aromatic or aliphatic sulphonic acid with a cyanide with the synthesis of 2-substituted 4:5 dihydroglyoxalines (XXXIV) in good yields by heating the cyanides with the.sulphonic salts of a diamine. Rings containing 6 and 7 atoms were obtained.

XXXIV 16.

Another reaction for the preparation or amidines is the amin- ation of aliphatic and aromatic nitriles with alkali metal amides (XXXV), but it failed with nitriles containing reactive methylene groups as they underwent condensation to a dimer (25,26,27).

R- G=N + KNH -- RC=NK 2 1 NH 2

The reaction was carried out in anhydrous media such as benzene, xylene but in the case of the lower aliphatic nitriles, considerable polymerization at temperature of 60-70°C was observed. Propionamidine, n-val eramidine and propionamidine were isolated with 30 to 50% yields. The conversion of the alkali metal salta to the amidines was accomplished by careful hydrolysis with water at low temperature in order to prevent hydrolysis, or by treatment with hydrogen chloride in absolute alcohol

(28,29).

R-C=NK + ~0 RC=NH + KOH 1 Il ~ NH2

R-C=NK + HCl RC=NH.HCl + KCl 1 k2 NH2

Lottermoser (30) and others (14) treated the free amine with powdered sodium and the isolated sodium salt of the amidine was converted to the free base with water hydrolysis. 17.

+ 2Na

XXXVI

(XXXVI) + ~0 __..,.

The importance of this method is obvious as o-toluenenitrile does not react by Pinnerts process. In general, amidines are not produced by the addition of a.mm.onia or an amine to an unsubstituted cyanide, but the introduction of certain polar atoms or groups facilitates the addition of the amine or other groups to the carbon-nitrogen triple bond. HYdrochloric acid seems to be necessar,y in the formation of imidic esters for alcohols and nitriles but Steinkopf (31) reported trichloroacetonitrile as an exception; it forms imidic ester with methanol and ethanol without the presence of halogen acids by heating the two reactants for five hours.

When Curtis and Nickel (71) added an ethereal solution of benzylamine in a solution of ethyl cyanotartronate (XXXVII) in ether, white crystals separated in fifteen seconds (XXXVIII). 18.

(XXXVII)

(XXXVIII)

This addition product was extremely soluble in acetone chloroform, methyl alcohol and benzene and so unstable that it decomposed to a tarry mass when kept at 25°C or exposed to the air. Ammonia and other secondar,y aliphatic amines gave addition compounds with the ethyl cyanotartronate but they were too unstable to be isolated. Only the products with the diethyl and di-n-propyl amines were obtained and characterized, while aniline and aromatic amines were round unreactive. 19.

Dachlauer (32) obtained trichloroacetamidine (XXXIX) by allowing trichloroacetonitrile to react with liquid ammonia at low temperatures but he gave no details for the preparation of a few other trichloroacetamidines by a similar process.

Cl CC:N + NH ----+ Cl CC,?NH (XXXIX) 3 3 3 "'~

NH Il CH- NH-C-CCl 2 3

CH=---z NH-C-CCl,, 3 NH

(XL)

A few years later Oxley (33) repeated Dachlauer's reaction and failed in attempts to employ aromatic amines for these addition reactions. 20.

The Chemistrr of Trichloroacetonitrile

Trichloroacetonitrile is prepared by dehydration of the tri chloroacetamide by phosphorus pentoxide or phosphorus oxychloride (34,

35,36,37,3S), chlorination of the acetonitrile in the presence of iodine (39,40) and by the action of thionyl chloride or chlorine in the presence of catalysts on acetonitrile (41) at temperatures of 320-340°. It is a colourless lachrymatory and toxic liquid (42), b.p. 85.7•, which should be hydrolyzed by heating with alcoholic ammonia to the trichloroacetamide. Boiled with methanol, it forms trichloroacetiminomethyl ether even without the catalytic effect of hydrogen hydrochloride, the presence of which causes hydrolysis (43).

When it is heated with absolute ethanol on a water bath in the presence of some acetone, it gives trichloroacetiminoethyl ether

(44). With phenols in ether and hydrochloric acid, the hydrochlorides of the corresponding trichloroacetiminophenyl ethers (45), and with methyl-mercaptan and hydrogen chloride in closed tubes the hydrochloride of the trichlorthioacetiminomethyl ether (46), are !ormed.

Cl C C~ N + CHJOH heat Cl C -w-OC~ 3 3 ~

Cl C-C=N + C H 0H heat Cl-C-C-OC H 3 2 5 acetone -y Il 2 5 ~ 21.

he at closed tubes HCl ~ Cl C-G-S.CH 3 Il 3 NH.HCl

Houben and Fisher (43,47) obtained trichloroacetophenonimide (XLI) from benzene and trichloroacetonitrile in the presence of aluminum trichloride and nydrogen chloride and they isolated the corresponding ketimides carrying out si.milar reactions with other aromatic hydrocarbons, as well as with thiophene.

Al Cl c H .H + Cl CC=N J 6 5 3

(XLI)

The ketimide for.med may be hydrolyzed to a ketone in acid media, and under the influence of alkalies produced a nitrile.

Condensation reactions with aromatic and heterocyclic compounds were reported by the same two workers, but these reactions could only 22.

take place with such catalysts as zinc chloride and hydrogen chloride1 or both, and aluminum trichloride (48,49). Alkoxy-dichloroacetonitriles were the main products from the reaction of sodium alcoholates and trichloroacetonitrile (50) which also form addition compounds with aluminum trichloride (51) and hydrogen bromide (50) •

RONa + Cl- CC12 C=.N ~ R-0-CC~ C:N + NaCl

At high pressures it is almost quantitatively po~erized to 2,4,6- tris(trichloromethyl)-5-triazine (XLII), m.p. 96° (52).

N Cl C-C/ ~C-CCl HCl 3 3 pressure Il 1 N, §N 'c -?" 1 CC1 3 (XLII)

Steinkopf and Bohrmann (43) found that with hydroxylamine under cooling

c1 cc~~~ and at 65° a dioxine of the foll trichloromethyl-amidoxine1 3 1 NOH owing formula are produced.

Cl- c-c-NH_ Il \\ ---~ NOH NOH

The reaction with ammonia and amines points out the ease of the addition of the -NH2 group due to the inductive effect of the three chlorine atoms. 23.

Dachlauer (52) allowing trichloroacetonitrile to react with an excess of liquid ammonia at -40° obtained trichloroacetamidine, m.p. 41- 420. He also prepared n-propyltrichloroacetamidine, b.p. 111-112° at 15 mm Hg, ethyleneditrichloroacetamidine, m.p. 88-90°, stear,yltrichloroacet amidine, ben~ltrichloroacetamidine, m.p. 85-86°, cycloh~ltrichloroacet amidine and bis-trichloroacetamidine.

In 1947 Oxley (33) passed dry ammonia for two hours at 0° into a solution of trichloroacetonitrile in benzene. After the distillation of the solvent in vacuo at 0° an oily product was isolated and neutralized with ethanolic picric acid to its trichloroacetamididrium picrate, yellow needles m.p. 273-275° (dec.). N-ethylene-bistrichloroacetamidine, m.p. 97-98° and the bipic rate salt, m.p. 178° (dec.) was also produced by the above-mentioned author and his co-workers, but their attempts to obtain the aniline derivatives were unsuccessful (33). The Reaction of fYridine with Bromine

The bromination of pyridine was usuall.y accomplished by a vapour-phase process according to Wibaut and Hertog (53) which involved the reaction of bromine with pyridine at 300°. The two reactants were passed through a tube maintained at this temperature. The product was a mixture of 3-bromo-pyridine and 3,5-dibromo-pyridine. When the

temperature was raised to 500° 1 2-bromo-pyridine was the principal product, according to McElvain and Goese (54). They also tried to brominate p,yridine by liquid bromine; the product was an orange-coloured pyridine perbromide, which when heated to around 250° underwent auto-bromination to give brominated pyridines. About one half of the pyridine was converted to a black tar which was also the main product from the vapour-phase reaction. The black tar for.med in the reaction was a hydrobromide which was quite soluble in water; the free base which was obtained by treating the tar with alkali contained no halogen and had no melting point. An elementary analysis gave the following values: carbon 75%, hydrogen 5.2% and nitrogen 17%. The tar gave a deep-red solution with alcohol and from these facts McElvain assigned a pol.ypyriQyl structure. Varying data were obtained concerning the composition of the perbromides of pyridine. Anderson (55) assigned c H NBr to the compound which he obtained 5 5 by treating pyridine with bromine in an aqueous solution.

Grimaux (56,57) allowed pyridine to react with three times its volume of bromine; he obtained a red crystalline, unstable compound which melted at 126°; he assigned the formula (C5H5NBr2)HBr. 25.

Trowbridge and Diehl (58) were unable to obtain a definite compound by allowing bromine to react with an aqueous solution of pyridine. By using chloroform as a solvent they obtained a dark-red crystalline compound which melted at 58.5° and analyzed for c H NBr • 5 5 4 This compound was unstable, and, on standing, lost bromine with the subsequent formation of H NBr , m.p. 94-95°. c5 5 2 In the same communication Trowbridge and Diehl obtained a very stable orange compound which melted at 125°. This compound was prepared by aspirating bromine through a water solution of pyridine hydrobromide until the original crystals dissolved in the excess of bromine. They assigned the following product; (C H NHBr) Br • This 5 5 2 3 may have be en the same compound which was isolated by Grimaux; however, Trowbridge and Diehl's compound was stable even when heated on a water bath, while Grimauxts product was very unstable. Also reported by Trowbridge and Diehl (58) was a compound c H N.HBr.Br which they 5 5 obtained by allowing pyridine hydrobromide to react with bramine in chloroform. By allowing bromine to react with an aqueous solution of pyridine hydrobromide they obtained two products, (a) containing 41.95% bromine which was a mixture of H N.HBr.Br and H N.HBr.Br c5 5 2 c5 5 and (b) containing 33.66% bromine which was assumed to be c H NHBr.Br, 5 5 m. p. 93°. Hoffman (59) allowed pyridine hydrochloride to react with bromine; the product was an orange-yellow crystalline substance. He did not analyze the compound, however, he suggested that the material was pyridine perbromide c H N.Br • 5 5 2 McElvain and Englert (60) improved Trowbridge and Diehl's 26. method for the preparation of the pyridine hydrobromide perbromide. They used glacial acetic acid as the solvent for the reaction. By using equimolar amounts of bromine and pyridine hydrobromide they obtained a product which ana1ysed for c H NHBr.Br, m.p. 132-135°. By 5 5 using a 2:1 ratio of pyridine hydrobromide to bromine, a product was obtained which was probably c H N.HBr.Br, m.p. 101-103°. The first 5 5 product, which melted at 132-134° when heated to reflux temperature, gave a 40% yield of 3,5-dibromo-pyridine. The lower melting product under the same treatment yielded 36% of 3-bromo-pyridine and 36% of 3, 5- dibromo-pyridine.

Williams (61) prepared pyridine perhalides by slowly adding the calculated volume of halogen in carbon tetrachloride to the cal culated volume of pyridine in the same solvent. Using bromine, he prepared p,rridine dibromide H NBr which was an orange-red cr,ystalline c5 5 2 compound and decomposed on standing; it could not be recr.ystallized, m.p. 62-63°. Pyridine perbromides as brominating agents

Pyridinium bromide dibromide, c H N.HBr.Br , may be consid 5 5 2 ered as a general brominating agent which can be used in brominations ordinarily performed with molecular bromine. It possesses many advantages over this dangerous liquid. A good deal of experimental work, alreaqy reported, seems to verify the efficacy of the above perbromide as a substitute for bromine (62,63,64,65,66).

It was used by Rosemund et al. (67) for bromination of phenols and double bonds.

Djerassi and Scholz (68) carried out brominations of 3- and 12-ketosteroids by warming equimolar quantities of the perbromide and ketone in glacial acetic acid or ethanol on a micro- or semimicro scale; they also brominated, by similar procedures, aliphatic and alicyclic ketones, but failed in attempts to employ pyridine dibromide, c H N.Br • This proved unsuccessful because warming caused poly.meriz- 6 5 2 at ion. Dombrovskii ( 69) reported that bromination of the styrene with pyridine dibromide in ethylene chloride gave 70% of styrene dibromide with 7-8% of the bromine being consumed for substitution; analogous behaviour was observed by the same author in preparations of the isoprene tetrabromide from isoprene, and Br-CH -c(cH )-COOH 2 3 Br from ""-methylacrylic ac id.

Recently acetylated hesperidin (XLIII) and naringin (XLVI) have been been converted into diosmin (XLV) and apigenin-7-rhamnoglucoside 28.

(XLVIII), respectively, by treating with pyridinium bromide dibromide in the presence of benzoyl peroxide as a catalyst, followed by removal of hydrogen bromide and acetyl groups with alcoholic alkali; the experimenta failed in the absence of the mentioned peroxide.

OAc 0

(XLIII)

OAc 0

(XLIV)

-HBr (XLIV)

R = Rhamnoglucose

(XLV) 29.

RO OAc

(XLVI)

j OAc

'---.J

(XLVII)

RO OH (XLVII) -HBr

R = Rhamnoglucose (XLVIII)

Metro (70) treating aniline with pyridine dibromide in acetonitrile solution obtained crystals of the aniline hydrobromide. Under the same conditions Metro found that o-toluidine and cyclohe:xyl amine amine formed salts with hydrobromic acid. He suggested the following scheme: Br 1 N-H 30.

DISCUSSION

PART I Reactions of PrimaEY Amines with Trichloroacetonitrile Unsubstituted nitriles show resistance to the addition of other substances across the carbon-nitrogen triple bond and there is no record of the formation of an amidine. in· the reaction . of ammonia or amines with an unsubstituted cyanide. Welter and Grossmann (73) stated that they obtained N-0-chloro phenylbenzamidine in 75% yield by heating benzonitrile and o-chloroaniline at 180°,but repetition of the reaction by Oxley and Short (24) failed to yield any arnidine. All the general methods for the formation of amidines described in the literature are based on the catalytic influence of acids or special catalysts; thus, Pinner prepared amidines by allowing the imidic esters hydrochlorides to react with nitriles; the use of amine salts with hydrochloric acids is limited and it proceeds at relatively high temper atures and often in closed tubes; Oxley and Partridge's process needs cyanides and the sulphonic acid salts of ammonia or amines. The reactions of the ammonium or alkylammonium thiocyanates and the nitriles take place under similar conditions. Temperature is a critical factor in all these reactions which do not occur at room temperature independently of the ti.me factor.

Bauer and Teter (74) passed a stream of ammonia through a solution of chloroacetonitrile (XLIX) in aqueous ammonia; they isolated no amidine but aminoacetonitrile (L) in 38% yield. 31.

XLIX L

Substitution of hydrogen atoms of the acetonitrile by two -COOC H groups and one hydroxyl group increases the reactivity of the 2 5 compound; thus, when Curtis and Nickell (71) added an ethereal solution of the benzylamine to a mixture of ethyl cyanotartronate (XXXVII) in ether, the formed diamidine (XXXVIII) separated in 15 seconds. Ammonia and ether aliphatic amines were used by the same workers, but their addition products with the cyanotartronate were too unstable to be isolated. Only compounds with the diethyl- and di-n-propylamine were obtained and characterized. The electronegative substituents are, of course, responsible for the instability of the prepared amidines.

~~en the hydrogen atoms of the alpha position of the cyano group are replaced by the electronegative chlorine atoms, their inductive

(-Is) effect enhances the reactivity of the carbon-nitrogen triple bond.

N-methyltrichloroacetamidine was isolat ed in this work from the reaction of methylamine (25% in water solution) and trichloroacetonitrile at room temperature; the reaction was strongly exother.mic and the mixture started boiling when the mixing became too fast. The liquid product preci pitated from the soluti on and was i nsoluble i n water but soluble in alcohols, ether, acetone and chloroform. It had a characteristic bad smell and attempts to distill it at normal pressure failed even in a nitrogen atmospher e. 32.

The colourless liquid turned yellow, red and black-brown and a violent reaction started before its boiling point, which was soon out of control. The black liquid was blown off and finally solidified into a black solid tar.

The same phenomena were observed during an attempt to distill

N-ethyltrichloroacetamidine which was obtained by a similar procedure under the same conditions. Both liquids are, however, stable enough at room temperature and distill without decomposition at low pressures and in an inert atmosphere.

N-benzyltrichloroacetamidine was isolated b,y conducting the reaction at room temperature either with or without methanol as a solvant.

N-phenyltrichloroacetamidine (LI) was obtained during this investigation in 90% yield by simply mixing the aniline and the trichloroacetonitrile in methanol; the mixture was left for 3 days at room temperature and the almost pure crystals were collected by filtration, m. p. 102°. The N-phenyltrichloroacetamidine hydrochloride melted at 183°.

c H NH + c1 ccN- c H cc1 (LI) 6 5 2 3 6 5NHR -- 3 NH

It must be noted here that Oxley and his co- workers (33) did not obtain any product by heating the two reactants for one hour in benzene.

The same compound was prepared by Steinkopf (75) who allowed aniline to react with the salt of the imidic ester of the trichloro- 33. acetonitrile according to Pinner's method; it showed a m.p. of 101° and it was characterized by its hydrochloride salt m.p. 183°. As qualitative reactions indicated this method is general for primary amines of the formula R-NH , where R=H, or alkyl or aryl or 2 aralkyl or their substituents; diamines may also be used. It has the advantage that it can be carried out in non-anhydrous media and water can be used as a solvent. No low temperatures are necessary, no special equipment and no heat; all the preparations were conducted at room temperature in the simplest way and high yields were obtained.

These are very interesting factors from the economie point of view. There is enough experimental evidence to indicate that monosubstituted amidines exhibit tautomerism; this is supported by the fact that the alkylation of an amidine yields two products (76,77,78,79) and the hydrolysis of N,N-substituted amidines produce a mixture of amines and amides (80).

Further, there is not a single case of the isolation of two pure tautomeric forms of a mono- or disubstituted amidine (81,82). Thus, Pechmann (83) obtained the same product by the following reactions.

+ .HCl - .HCl

The inductive (-Is) effect of the chlorine atoms may facilitate the tautomeri c shift in the case of N-substituted trichloroacetamidines. 34.

Amidines containing at least one hydrogen atom on the nitrogen are associated to sorne extent (84) and this may be explained by the assumption that hydrogen-bonding occurs together with resonance stabilization, which is observed with carboxylic acids. Bydrogen bonds may exist to a greater extent in trichloroacetamidines, due to the inductive E-3:s) effect. They may be responsible for the high boiling points observed and the broadening of the absorption bands in the infra -1 red spectra at the region 3500-3050 cm. •

H Rt /N1 ...... H-N""1

c13c-c""' / c-cc13 N--H ••••••• N 1 1 Rt H - il - H Rt 1 1 N- H••••••• N / ~ Cl3C-C' /C-CC13 N••••••• H- N 1 1 Rt H 35.

Reaction of trichloroacetonitrile with hydrazine When hydrazine hydrate was added dropwise to trichloroacetonitrile a vigorous reaction was observed with the evolution of a gas; the mixture turned yellow and a considerable amount of heat was evolved.

The reaction was carried out at 0°; a non-cr.ystalline material precipitated and decomposed immediately to a tarry black-brown mass when left at room temperature. No products were isolated.

Another attempt was made at room temperature; an alcoholic solution of hydrazine hydrate was added to trichloroacetonitrile in ethanol over a period of 7 hours. The mixture was stirred continuously and evolution of gas was noted which had neither the ammonia nor the hydrazine odour. The liquid layer which separated deposited colourless needles together with a yellow rather amorphous substance. The crystals were analyzed for N H .HC1, m.p. 94-94.5°. They also gave a precipitate 2 4 with silver nitrate. However, the m.p. of this salt has been reported 68.5° in the literature. The easy addition of the amino group to the carbon-nitrogen triple bond of the trichloroacetonitrile and the fact that a compound separated at 0° with subsequent decomposi t i on may suggest the following scheme of the reaction.

LII

(LII) + Cl CCN --tor Cl CCNHNHCCC1 3 3 ,, Il 3 NH NH

LIII 36 •

. hydrolysis~ Lili NH2NH2.HC1 + gas + •••

The !act that the alcohol used was not absolute and the expected instability of the addition compounds (LII) and (Lili) may facilitate the hydrolysis. HYdrazine monohydrochloride was also isolated by Oberhummer (B5) who treated ethyl formamidate hydrochloride (LIV) and anhydrous hydrazine in absolute ethanol. ~H2 N-CH hydrazine EtOCH=NH.HCl HG/ Il + NH4Cl + H2~.HC1 'N-N

(LIV)

A few aspects of the reaction mechanism In the absence of physico-chemical data, no suggestion for a mechanism is possible. However, a few aspects may be useful in the investigation of the reaction of the primary amines with the trichloroacetonitrile. Knorr (16) reported that Pinnerts reaction involved an ammonium ion; the reaction mechanism is probably similar to that suggested for the hydrolysis of esters and the first step is an attack of the nucleophilic reagent t o the positi ve carbon centre. -S e NH NH NH Il 1 1 R- C-ORt ---. R- C-ORt R- C-OR' ~ R- C=NH + ROH 1 1 @ NH NH +b 3 2 37.

Oxley and Short (21) in a study of the reaction of the nitriles and the salts of the amine with an aliphatic or aromatic sulphonic acid assumed that an equilibrium was established between the reactants, their complex intermediate "capable of degrading the ammonium ion, probably by hydrogen bond formation between nitrogen atoms", and the produced amidinium salt.

n + ~+ R- C=N R" fi.TH ;:::::? R-C- NHR" 3 Il NH

The same authors suggested the probability that by controlling the reaction temperature "many cyanides would combine with ammonia or amines to yield amidines, but that only in exceptional cases would sufficient amidine be present at equilibrium to make the reaction of value as a method of preparation. Since amidines are usually stronger bases than ammonia or amines, it seemed probable that if the reaction were carried out in the presence of an ammonium salt, an amidinium salt would be formed, and provided that the temperature was lower than that at which this salt dissociates, the equilibrium would be disturbed and the conversion of the cyanide into the amidine would be promoted".

(±) GJ R-C=N + NHXY -- R-C-NXY .., NH2XY., R-C-NHXY + NHXY • • • • li Il NH NH

The reactions of the trichloroacetonitrile with the primary amines occur almost irnmediately and are strongly exothermic with the aromatic amines as an exception. 38.

Solvents such as water, methanol, ethanol, or mixtures of these had no influence on the velocity of the reaction; thus the formation of the N-benzyltrichloroacetamidine was complete in one minute when the trichloroacetonitrile and the benzylamine were allowed to react in a methanol, or a water-methanol mixture, or in the absence of both.

+ Cl3CCN ~ c 6H5 cH2 NH~CC13 NH The molecule of the trichloroacetonitrile is a strong dipole with a dipole moment of 1.93D., according to Davies and Jenkin (72), which was measured in terms of the dielectric constant, refractive index and the density of the pure liquid. On the assumption that the group moments are constant, this value should be equal to the difference between the moments for acetonitrile and chloroform, which is 2.1 D., and the agreement is not unreasonable. From a careful examination of the molecular structure of the trichloroacetonitrile it can be assumed that the carbon atom of the carbon-nitrogen triple bond is the centre of electron displacements in the opposite directions.

Cl •• <±> •• e CC1 - C= N: Cl~C 3 Cl/

The three strongly electronegative chlorine atoms of the trichloromethyl group attract the electrons of the carbon atom to which they are attached, and impose on it a partial positive charge; this 39. inductive effect can be transmitted to the carbon atom of the nitrile group to an extent of 10-30% of its value.

At the other end of the molecule the nitrogen atom produces a shift of the 7T electrons of the triple bond to the opposite direction.

A very small fraction of these two effects, of course, can be transmitted to the two ends of the molecule but this further shift may be neglected. These effects doubtless account for the enhanced reactivity of the trichloroacetonitrile in the Hoesh reaction, for the decomposition suffered by the trichloroacetic acid in boiling water and the alkaline hydrolysis of the chloral.

Cl CCOOH 3

On the other hand the mobility of the nitrogen's unshared electron pair of the primary amines is increased by the inductive effect of the alkyl substituent and its affinity for a positive centre.

The above-mentioned effects may not make imperative the following mechanism scheme for the reaction of primary amines and the trichloroacetonitrile.

Cl' +s -S •• c1--- c--- c==N: + • • \..,./1 Cl/ V H2 N-R 40.

c1"" e c1~ e Cl--C- C===N: Cl-- C-C ===N: ____,.. / 1 •• / H-N-H / '· -~::J Cl ~ Cl rn:· f1 R

Cl Cl-C-C=NH "'/ 1 •• Cl H~ R

It may be assumed that the attack of the base through the unshared electron pair, the liberation of the proton and its migration, take place very quickly or synchronously in one step, if we consider the high velocity of this reaction between the cyanide and the primary aliphatic amines.

Chemical indications were observed in support of this mechanism which, of course, cannet be postulated in the absence of pnysico- chemical data. \fuile the ethylamine and methylamine hydrochlorides were allowed to react with trichloroacetonitrile at room temperature for two hours and under the same conditions which led to the quick formation of the amidines, no heat effect was noted and the reactants were recovered in almost quantitatively unchanged yields. The methods described in the literature for preparation of the amidines involve the use of amine salta and nitriles. Thus Pinner's method is based upon the reaction of the salts of the imidic esters and ammonia or amines; the use of amine salts and nitriles is not general, and it proceeds at high temperatures in sealed tubes and with very poor yields. Oxley and Partridge's process needs cyanides and the sulphonic 41. acid salts of the ammonia or the amines, and a temperature in the neigh- bourhood of 200°; the reaction of the ammonium or alkylammonium thiocyanates and the nitriles occur with similar conditions, and the fact that these salts may dissociate under these circumstances cannot be ignored. However in the absence of acids or special catalysts no reaction could take place regardless of the conditions used.

The resistance of the carbon-nitrogen triple bond of the trichloroacetonitrile to the alkylammonium salts is obvious if the reaction proceeds according to the proposed mechanism. In these salts the electron pair is shared with the proton and it is not available.

Cl ~ Cl-c-c-N:

Cl/ H + 1 R-N:H 1 H

While the reaction of the primary aliphatic amines occurs in a few minutes, it took three days for the aniline to react in a similar manner, under exactly the same conditions; aniline has a basic dissoc iation constant of 5 x 10-lO and the ~ for the aliphatic amines is of the order of 10-4; the lower basicity of the aniline or, in other words, the lower mobility of the unshared electron pair may be responsible for the decreased reactivity of the aromatic amines; benzylamine, of course, resembles the aliphatic amines and it shows analogous reactivity. The smaller basic dissociation constant is ea.sily explained by the resonance molecular theory. The various electronic structures which corrtribute to the resonance hybrid of the aniline molecule introduce a partial positive 42. charge to its nitrogen atom.

- O-~ 0 -0 n. Il Il+ N N+ N 1 \ 1 \ 1 \ H H H H H H

The strict coplanarity of the aniline has not yet been established experimentally, but it has been found that the three bonds around the nitrogen atom are more nearly coplanar than in ammonia, while not achieving complete coplanarity.•

If the mechanism described is true, substituents of the phenyl ring which act as electron-acceptors, e.g. p.N02 must retard the formation of the trichloroacetamidines which must be promoted by those which act as electron sources; the mobility of the unshared electron pair increases by the influence of the first, and decreases by the influence of the others. It should be noted here that Oxley and Short (21) found that the preparation of amidines from phenylcyanides was usually promoted by groups acting as electron acceptors and retarded by those which are electron sources; it is obvious that the presence of electron-withdrawing groups increases the positive charge of the reacting carbon centre and facilitates the reaction, while electron-releasing substituents diminish this positive charge and inhibit the course of the reaction.

The stuqy of the kinetics of this reaction may become easy and 43. accurate by means of the infrared spectroscopy in the case of the aromatic -1 amines. The intensity of the absorption band at 2250 cm. which is given by the carbon-nitrogen triple bond must decrease with time, and it should be proportional to the decrease of the concentration of the cyanide which disappears. This may be a measure of the decrease in concentration of the reacting amine and the increase of the concentration of the product may be computed; the reaction is a simple addition which involves two reacting species, one per one stoichiometrically and one as a product. Nevertheless the reaction of the trichloroacetonitrile with aliphatic amines is too fast to be measured.

Effect of the trichloroacetamines of the skin

During this research it was observed that the trichloroacetamidines which were prepared caused a kind of dermatitis when they came in contact with the skin. Blisters developed in a few hours which in some cases covered the whole area of the skin causing a strong itching.

This condition lasted 1-2 weeks, depending on the original length of contact of the skin with the liquids or their solutions. The concentration of these solutions influenced the development of the blisters.

Quick removal of the attacking liquids from the skin with solvants such as methanol or ethanol did not prevent the development of this skin condition. PART II

Reaction of Pyridine Dibromide with Aniline

Three of the five valence electrons of the nitrogen in pyridine are shared by the two adjacent carbon atoms and the remaining two are present as an unshared electron pair, responsible for the characteristic reactions of pyridine and its derivatives, such as the formation of salts with acids, complex formation, oxidation to amine oxides, and formation of N-alkyl and N-ar.yl-pyridinium compounds.

The unshared electron pair of the nitrogen atam is still available in the pyridine dibromide and this can be illustrated by the fact that pyridine dibromide forms a crystalline salt with hydrogen bromide.

HBr

The bromine in either of these two compounds is loose~ bound and pyridine perbromides have been used as mild brominating agents, although the pyridine dibromide proved disappointing, because warming caused po~erization (68). When aniline or other aromatic amines are added to an aceto nitrile solution of pyridine dibromide, a vigorous and complicated exo thermic reaction starts immediate~. At first bromine attacks aniline with the liberation of hydrogen bromide according to the following scheme. 45.

3C H N.Brz + + + 3HBr 5 5 - 3C 5H5N 0 Br Br NH2 NH2

Aniline, a base stronger than pyridine or the 2,4,6-tribromoaniline, picks up the hydrogen bromide and the aniline hydrobromide, insoluble in this mixture, precipitates. The bromination of the aniline and the formation of its hydrogen bromide salt are strongly exothermic reactions. The temperature of the mixture increases rapidly, while at the same time pyridine is gradually liberated. Under these conditions the rapid exothermic po~erization which McElvain investigated in 1953 starts at once.

According to his report (54) when pyridine dibromide was heated up to 70° in an excess of pyridine, a black tar was formed which was quite soluble in water; the free base which was obtained bybreating the tar with alkali contained no halogen and bad no melting point. This polymerization product gave a deep red solution with alcohol and, from these facts, McElvain assigned a polyp,yridyl structure. The linkages were not necessarily through the alpha positions and could have been represented as joined through the gamma position. - 0N - H 0N 0 + 46.

etc •

• • • OOr OOr ~r

The liberated hydrogen bromide may facilitate this polymerization. The fact that the precipitated aniline hydrobromide was pink- coloured may now be explained. It is possible for this salt to absorb preferentially the formed polypyridyl red colour of McElvain. The persistence of this colour during the repeated recrystallizations may support the above explanation.

The formed 2,4,6-tribromoaniline was isolated from the black reaction mixture and was recrystallized three times from methanol-water,

Sodium fusion tests showed the presence of bromine and nitrogen. 47.

The structure was proved by testing the derivatives:

Derivatives of Observed m.p. Reported m.p. 2,4,6-tribromoaniline oc. oc.

2,4,6-tribromoacetanilide 232-232.5 232

2,4,6-tribromobenzanilide 198-199 198 2,4,6-tribromoformanilide 221.5 221.5

Correlation between the infrared spectra and structure of the N-substituted trichloroacetamidines

Region 3500-3000 cm. -1 According to the general formula of N-substituted trichloroacetamidines

there must be absorption bands due to the secondary amine group NH and to the irnino group NH in the stretching region between 3500-3000 cm.-1• Usually secondary amines give only one band between 3500-3300 cm.-l of medium intensity, which may be subject to changes by hydrogen bonding affecting this group. Imines give one band almost in the same region -1 at 3400-3200 cm. Randal et al. (86) have assigned a range of 3500-3050 cm.-l for the N-H vibration in solid substances.

However, secondary amines at high concentration may show a second band at lower frequences corresponding to the NH stretching ~. frequency which increases in intensity with concentration and in the absence of solvent, replaces the free N-H band almost completely. The infrared spectra of four N-substituted trichloroacetamidines were taken in liquid or solid phase and results have been summarized in

Table I. The N-methyl derivative shows a strong band at 3485 cm.-l and -1 another one possessing three separate peaks at 3340, 3310 and 3270 cm. • The N-ethyl derivative shows two very strong bands at 3470 and 3340 cm.-l 1 and a shoulder at 3200 cm.- • Two strong absorptions at 3480 and 3370 cm. -1 and a third one of weak intensity were recorded for the N-phenyl compound. The N-benzyl derivative showed only two strong bands at 3335 and 3205 cm. -1 • The first band of the four compounds may be attributed to the secondar,r NH group while the appearance of more than two bands may be due to the =NH stretching modes and to hydrogen bonding effects on these groups.

In all four infrared spectra of the above-mentioned substances there are bands at 3050 or 3030 cm. -1• They are weak with one exception only for the N-benzyl derivative. In N-methyl and N-ethyl compounds these bands probably arise from hydrogen bonded N-H groups while for the other two substances they may also originate from C-H aromatic stretching vibrations.

Region 3000-2000 cm. -1 The asymmetrical and symmetrical stretching vibrations of the CH group absorb strongly at 2962 and 2872 cm. -1, but in additi on one or 3 two weaker intermediate frequenci es were reported in sorne cases (88).

The methylene group gives rise to two characteristic bands at 49.

2926 and 2853 z 10 cm. -1 corresponding to the symmetrica1 and asymmetrical vibrations of the hydrogen atom.

The r~methyltrich1oroacetamidine showed two weak maxima at 2960 and 2870 cm. -1 for the -cH in-phase and out-of-phase modes respect- 3 ive1y and one weak one at 2910 cm.-1• From these two vibrations, the first appeared very strong at 2985 cm. - 1 and the second of medium intensity -1 -1 at 2875 cm. for the N-ethy1 derivative, of which the 2940 cm. (ms) band may be considered as the CH2 symmetrica1 frequency. The two characteristic bands for the methylene group absorption appeared as a shou1der at the spectrum of the N-benzyl compound at 2970 and 2810 cm.-1•

Region 2000-1600 cm. -1

The C=N stretching absorption in open-chain systems shows only one strong band within the range 1690-1640 cm.-1• The N-H deformation band which is strong in primary amines is usually extremely weak in secondar.y amines and appears in the region 1650-1550 cm.-1; the intensity of this band however seems to increase in a few exceptiona1 structural combinat ions. Thus, N-H deformation is believed by many workers to be enhanced in open-chain secondary amides b,y the presence of a CO group, so that it is responsible for the amide II band, but this assumption is sti11 a matter of controversy (89).

The N-methyl- and N-ethyltrichloroacetamidines showed one strong 1 band at 1672 and 1662 cm.- , respectively, which may be attributed to the

C· N frequency; the same vibration occurs at 1680 cm. -1 for the N-phenyl derivative. 50·

The second very strong band in this region possessed two separate peaks at 1640 and 1630 cm.-l for the N-methyl and at 1640 and 1627 cm.-l for the N-ethyl derivatives; these absorptions may be due to the secondary, N H, and imino, ~N H deformation absorptions as both groups are present in the substances examined. However, this second band was very strong at 1660 cm. -1 for the

N-phenyl while the N-benzyl compound showed only one very strong minimum at 1635 cm.-l in this region.

-1 Region 1600-1550 cm. -1 The two very strong absorption maxima recorded at 1595 cm. and -1 -1 1585 cm. for the N-phenyl- and the one at 1605 cm. for the N-benzy1 derivatives are due to the aromatic ring vibrations.

Region 1550-1500 cm. -1

New bands were shown in this region by the four compounds e~ -1 ined; thus, one strong band at 1525 cm. for the N-methyl and two strong absorptions at 1532 and 1515 cm.-l for the N-ethyl derivative were -1 recorded. N-phenyltrichloroacetamidine showed a shoulder at 1542 cm. while the N-ben~l derivative absorbed definitely at 1543 cm.-1• Although there is no information in the literature, correlations between the structure of these compounds and absorption maxima in this region are presented in this discussion and sorne interesting aspects may be reported from a comparison of the general formulae of the prepared amidines with the aliphatic open-chain secondary amides, 51.

R-CH -N-C-CC1 R'CH -N-C-R" 2 1 Il 3 2 1 Il HNH H 0 where R = hydrogen, methy1, pheny1 or benz.y1 groups. The amide I for C=O and the amide II bands for secondary non cyc1ic amides have been reported in the vicinity of 1680-1630 cm.-l and -1 1570-1515 cm. respectively. The simi1arity between these two types of compounds and the analogous effects of the nitrogen and oxygen atoms, as far as infrared spectra are concerned, might support the idea for the characterization of the N-substituted amiclines by the strong bands of amicline I near 1 40 cm. -l 1 and amidine II in the vicinity of 1530 cm.- • The observed strong absorptions of the N-H deformation frequency, which is usual1y very weak, may be corroboratory.

Unfortunately, there is but little information in this field and a great amount of work has to be done on the spectra of amidines.

Region 1500-1360 cm. -1 The CH group usua1ly shows one medium band at 1450± 20 cm. -1 3 corresponding to the asymmetrical b

1380-1370 cm. -1 for the symmetrical deformation frequency; this second band is shifted to higher frequencies when the methyl group is attached to an electronegative atom, e.g. 1418 cm.-1 in substances which have the

CHJ-N group (86). Absorption bands due to scissor vibrations of the methylene group 1 have been reported near 1465 cm.- , but this frequency is also subject to changes when an e1ectronegative atom is attached to the CH2 group. 52.

The N-methyl derivative showed two weak bands at 1465 and 1445 -1 -1 -1 cm. and one strong band at 1417 cm. ; from these the 1465 cm. is probably due to the CH asymmetrical bending while the third one is due 3 to the symmetrical bending vibrations of the methyl group in the CH3 N combinations. The 1445 cm.-1 frequency is rather associated with the CHJ deformations. These two CH bending modes appeared at 1463 cm.-1 (m) and 3 1378 cm.-l (ms) for the N-ethyltrichloroacetamidine, which also showed 1 another strong absorption at 1452 cm.- corresponding to the CH2 scissor vibrations. The ori.gin of the fourth medium band at 1.482 cm. -l is unknown. The spectrum of the N-phenyl derivative showed only two bands, -1 one strong, at 1485 cm. which may be attributed to the aromatic ring vibration, and one weak at 1448 cm. -1• From the four bands of the N-benzy1 derivative, the band at 1 1 1496 cm.- is due to the aromatic ring vibration and the 1452 cm.- band to the scissoring -CH2- frequency, to which may be associated the 1425 -1 cm. absorption for the CH2-N group. The rather wide frequency range within a11 these motions, together with the many skeleta1 modes, make the correlation difficult in this region.

Region 1360-1020 cm, -1 In this regi on, skel eta1 vibrations show strong absorption 1 -1 bands near 1170 cm.- and ll70-1140 cm. ; C-C and C-H frequencies are also between 1100 and 1000 cm.-1•

Aromatic monosubstit uted compounds absorb weakly at 1175-1125 cm.-1, 1110-1020 cm.-1, and 1070-1000 cm.-1• The C-N vibrations of the ~-

1 aromatic secondary amines give rise to a strong band at 1350-1280 cm.- and two weak bands appear at 1220-1020 cm.-l for the aliphatic amines (SB).

The N-methyltrichloroacetamidine showed a strong absorption at 1315 cm.-l which is due to the C-N vibration; two other bands at 1177 cm.-1 (ms) and 1152 cm.-l (vs) may be attributed to C-C frequencies. A fourth one was also observed at 1045 cm. -1 of very strong intensity. A series of seven bands was recorded for the N-ethyl derivative of strong to very strong intensities. The band at 1315 cm.-l could be correlated with C-N vibrations and the bands at 1165 and 1145 cm.-l to c-c modes. At this point it has to be noted that the possible migration of the hydrogen atom and the hydrogen bonding effect may give rise to new bands which have not been reported. The N-phenyl derivative showed a strong absorption at 1340 cm.-l which is due to C-N vibrations and a series of 5 more bands of weak to medium intensity. From these the band at 1170 cm. -1 may originate 1 from C-C frequency. The 1157, 1080 and 1030 cm.- absorptions arise from the monosubstituted benzene ring. The above-mentioned three frequencies appeared at 1170, 1080 1 and 1030 cm.- in the N-benzyl derivative spectrum; this compound absorbed at 1335 cm.-l (s) corresponding to the C-N frequency.

Region 1020-600 cm. -1 C-H rocking and C-C stretching vibrations give rise to absorption bands in this region but they are of limited value for the elucidation of 54·

the molecular structure. The presence of an electronegative atom in the molecule may influence the intensity and the positions of these bands but no definite correlations have been reported. Bending vibrations of the aromatic C-H group are observed between 1000 cm. -1 and 900 cm. -1 , while two 1 more strong absorptions occur at 770-730 cm.-l and 710-690 cm.- , corre1ated with the C-H aromatic modes of monosubstituted benzene rings, are given in the literature. The C-Cl absorption at the region 625-570 cm.-l is increased to

710-780 cm.-1 when two or three chlorine atoms are attached to the same -1 carbon atom (89,90). However, a further shift to 780-825 cm. was noted in all spectra exarnined.

It is expected that triha1ogen al~l groups might absorb with scissoring, wagging, twisting, rocking and bending vibrations comparable to those of the methyl and methylene groups, but there is no information for the trichloromethyl group. Nevertheless, C-Cl stretching vibrations absorb near 650 cm.-l also.

The N-methyl derivative showed two weak bands at 1008 and 915 cm.-l which might be due to C-H bond vibrations, and one very strong band which possessed two separate peaks at 820 and 785 cm. -1 corresponding to C-Cl in cc1 group stretching modes. The two weak bands observed at 710 3 and 682 cm.-l may be correlated to C-C modes. The 1ast band noted at 646 cm.-l was of medium intensity and is probably due to C-Cl stretching absorptions.

The N-ethy1 derivative showed six bands in this region. From these, the 948 cm.-l (m) and 900 cm.-l (s) frequencies are due to C-H bonding vibrations, the peaks at 820 and 782 cm. -1, which form one very 55. strong band, correspond to the C-Cl in cc1 stretching modes and the 700 3 cm.-l (m) and 640 cm.-l (s) may be associated with the C-C or C-Cl stretching frequencies. A series of twelve bands was observed for the N-phenyltrichloro acetamidine. The aromatic C-H bending bands appeared at 860 cm.-l (s), 895 cm.-l (ms) and at 760, 688 cm.-1• The C-Cl in cc1 stretching vib- 3 ration showed two distinct bands at 806 and 782 cm. -1 of strong and very strong intensity, respectively. Another strong band at 660 cm.-l may be correlated with the G-Cl stretching mode.

The N-benzyl derivative showed absorptions of 1008 cm. -1 (s) and 977 cm.-l (w) re1ated to C-H bending modes; the 917 cm.-l weak absorption and the 742, 705 cm. -1 strong bands may be due to C-H aromatic bending frequencies. A series of three strong to very strong bands at 828, 806 and 780 cm.-l are related toC-Cl in cc1 stretching bands; the 3 last absorption appeared as a shoulder at 665 cm.-l and is correlated to

C-Cl stretching mode. 56.

EXPERIMENTAL

Part I - Reaction of trichloroacetonitrile

Ethyl trichloroacetate

Through a mixture of 450 gm. of trichloroacetic acid (2.76M) and 164 ml. of absolute ethanol (2.76M) a strong stream of dry gaseous hydrogen chloride was passed for 3.5 hours. The mixture was cooled by means of an ice-water bath. At the end of this time separation into two layers was observed. The slightly yellow coloured lower layer was separated by œans of a separatory funnel and washed four times with distilled water until the washing waters gave no acidic reaction with blue litmus paper. The liquid was distilled at normal pressure and the fraction boi1ing at 166-167° was co11ected. Reported b.p. 167.5-168° {corrected). Yield 456 gm., B7%.

2,2,2-Trichloroacetamide

Ethy1 trich1oroacetate (480 gm.) was placed in a one-litre round-bottomed f1ask, and cooled in an ice-water bath.

A strong stream of ammonia gas was passed through the liquid ester for a period of four hours. Trich1oroacetamide started to precipit ate immediately in the form of fine co1ourless crystals.

The liberated alcohol was poured out and the product was dried by means of water and vacuum pumps. 57.

M.p. 136°; Yield 400 gm., 90%.

Trichloroacetonitrile

Trichloroacetamide (395 gm., 2.37M) was placed in a',two-litre round-bottomed Pyrex flask and mixed with about 340 gm. of phosphorus pentoxide (2.37M). The mixture was shaken well and left for six hours at room temperature. The f1ask was then connected for distillation at normal pressure and was heated gently by means of an electric mant1e.

The obtained trichloroacetonitrile was redistilled and the portion boiling at 86° was co1lected. Yie1d 252 gm., 75% of the theoretical.

N-Phegyl-trich1oroacetamidine

Fifty ml. of trichloroacetonitri1e (0.5M) and 46 ml. of freshly-distilled aniline (0.5M) were poured into a 300 ml. flask; to this mixture, 60 ml. of methanol and 25 ml. of distilled water vere added. The flask was closed and 1eft for three days at room temperature. The precipitated, almost co1ourless, cryetals were filtered and recrystallized twice from a methano1-vater mixture.

Yie1d: 107 gm., 90% of the theoretical, m.p. observed 101-102•, reported 101°.

Qualitative analysis showed the presence of nitrogen and ch1orine. 58.

The product was analyzed for its elements.

Ana1ysis

Found: C, 40.60; H, 3.07; N, 11.80%.

N-PheBYl-trichloroacetamidine nydrochloride

Through one gm. of N-phenyl-trichloroacetamine in 50 ml. of dry ether a stream of dry hydrogen chloride was passed. The precipitated salt was filtered off and dried in a desiccator. This salt turned a brownish colour 10-15° below its melting point and became darker as it neared the melting point; finally melted at 183° (decJ, reported m.p. 183° (dec.).

N-Methyl-trichloroacetamidine

To 15 ml. of a 25% water solution of methylamine, 8 ml. of trichloroacetonitrile (11.1 gm.) was added dropwise with a funnel over a period of ten minutes. The solution was stirred and the reaction became so exothermic that it had to be cooled with an ice-water bath.

During the addition of the trichloroacetonitrile, separation of a layer was observed. -When all the nitrile had been added the stirring was continued for two more minutes. The lower layer was separated by 59.

means of a separatory funnel, one gram of anhydrous sodium su1phate was

added and it was left overnight.

The so1id drying reagent was filtered off and the colourless

liquid was distilled at 129° and 60 mm. Hg pressure in a dry nitrogen

atmosphere.

Yie1d 11.5 gm., 86% of the theoretical.

Sodium fusion tests showed the presence of chlorine and nitrogen.

Ana1ysis

Calculated for c H cl N : N, 15.93; H, 2.90%. 3 5 3 2

Found: N, 15.85; H, 2.99%.

N-Methyl-trichloroacetamidinium picrate

To one gram of N-meth,yl-trichloroacetamid.ine in ten ml. of

distilled benzene an equimolar quantity of picric acid was added slowly.

The yellow needles of the salt precipitated; they were filtered off and dried.

The melting point of the crude product was 150-153°; after two recrystallizations from water it melted at 163-164°.

N-Etgyl-trichloroacetamidine

Into 10 ml. of a 72% solution of ethylamine in water 8.5 ml. of trichloroacetonitrile (12.1 gm.) was added dropwise, over a period of 60. ten minutes. The solution was continually stirred by means of an electric stirrer. The reaction became so exothermic that it had to be cooled with an ice-water bath. During the addition of the nitrile, separation of a layer was observed and the stirring was continued for two minutes after the addition of the last drop. The lower layer was separated with a separatory funnel, one gram of anhydrous sodium sulphate was added and the liquid was left overnight. The drying reagent was filtered off and the colourless liquid was distilled at low pressure in a dry nitrogen atmosphere. The distilled liquid was redistilled and the colourless transparent liquid boiling at 87-88° at 7 mm. Hg was collected. B.p. observed 87-88° at 7 mm.

Hg and 62° at 2 mm. Hg.

Yield 11.9 gm., 74% of the theoretical. It was analyzed for its elements.

Analysis Calculated for H Cl N : N, 14.77; H, 3.73%. c4 7 3 2

Found: N, 14.68; H, 3.75%.

N-Ethyl-trichloroacetamidine nydrochloride

Through one gram of N-ethyl-trichloroacetamidine in 30 ml. of dry ether a slow stream of dry hydrogen chloride gas was passed. The precipitated salt was filtered off and dried in a desiccator. Ten degrees 61. below its melting point the colourless salt became dark brown and melted at 222° (dec.).

N-Benzyl-trichloroacetamidine

I. Benz.ylamine (5.36 gm., 0.05M) was diluted in 30 ml. of methanol in a 100 ml. conical flask and cooled with an ice-water bath. Trichloro acetonitrile (7.22 gm.) was added dropwise with stirring over a period of five minutes. A considerable rise of temperature was noted. When all the nitrile had been added, fifteen ml. of distilled water was poured in. The product precipitated immediately and was separated by filtration.

The yellowish crudely crystalline compound (9.51 gm.) was collected and showed a m.p. of 76-81°. Recrystallization from petroleum ether was attempted, but the substance separated as a liquid on cooling. Another method of purification gave quick and very good resulta. The crystals were dissolved in a small volume of methanol and were precipitated by addition of distilled water dropwise with stirring. It showed a m.p. o:t 83.5° (obs.)

II. Into 3.57 gm. of benzylamine (l/30M) 4.81 gm. of trichloroacetonitrile was added in portions over a period of five minutes. The mixture was shaken vigorously; the reaction became strongly exothermic and the flask was cooled under running water. After a period of three minutes the liquid mixture solidified almost completely into a yellow mass. It was diluted with a small volume of methanol and precipitated by addition of distilled water dropwise with 62. continuous stirring. The obtained colourless cr.ystals melted at 83.5•.

Anal.ysis Calculated !or c H cl N : C, 42.98; H, 3.60; N, 11.19%. 9 9 3 2

Found: C, 43.22; H, 3.64; N, 11.19%.

Methylamine hydrochloride and trichloroacetonitrile

To 2.27 gm. of methylamine hydrochloride (l/30M) in a mixture of 10 ml. distilled water and 10 ml. of methanol, 4.81 gm. o! trichloro acetonitrile (l/30M) was added and the flask was kept at room temperature for two hours. The mixed substances recovered by fractional distillation were almost quantitatively unchanged.

Ethylamine hydrochloride and trichloroacetonitrile

A mixture of 2. 7 gm. o! ethylamine hydrochloride (1/30M) and 4.81 gm. o! trichloroacetonitrile (1/30M) in 10 ml. of water and 10 ml. of methanol wa.s prepa.red. The conical nask wa.s kept at room temperature for two hours. The four constituants of the mixture were recovered by fra.ctional distillation almost quantitatively unchanged. 63.

Reaction of }lydrazine and trichloroacetonitrile

I. Five ml. of hydrazine hydrate (85% in water) was placed in a small round-bottomed fiask provided with a small dropping funnel and a magnetic stirrer. The flask was cooled in an ice-water bath, and 20 ml. of trichloroacetonitrile was added dropwise over a period of 30 minutes with vigorous stirring. Precipitation of a rather amorphous material, slightly yellow-coloured, was noted.

In a few seconds after the whole portion of trichloroaceto nitrile bad been added, this yellow mass reached the surface of the liquid mixture and decomposed violently to a tarry black-brown mass with the evolution of a gas. No products could be isolated.

II. Eight ml. of hydrazine hydrate (85% in water) were diluted with

):) ml. of ethanol in a two-necked round-bottomed flask equipped with a dropping :tunnel and a gas trap. To this mixture a solution of 5 cc. of trichloroacetonitrile in 30 ml. of ethanol was added dropwise over a period of seven hours. A strong exothermic reaction and evolution of a gas was noted; the flask was kept at room temperature and was continuously stirred with a magnetic stirrer. The mixture, colourless at the beginning of the reaction, turned yellow and orange; a liquid layer separated; the whole system was left overnight at room temperature. The lower layer separated and deposited fine, colourless crystals and a yellow non-crystalline substance on the addition of a small volume (10 cc.) of ethanol. Both were filtered off and were separated by the addition of ethanol which dissolved only the colourless needles leaving the yellow amorphous material undissolved. The ethanol filtrate was concentrated by means of a water pump to a small volume and the precijr itated product was collected and recrystallized from absolute ethanol, m.p. observed 94-94.5°. A small portion of the substance in one ml. of distilled water was acidified with a few drops of nitric acid; one drop of 5% solution of silver nitrate in water showed the presence of chlorine anion. Qualitative tests proved the presence of nitrogen and chlorine.

Anal.ysi.s Calculated for NH Cl: N, 40.89; H, 7.36%. 2 5

Found: N, 40.71; H, 7.22%.

Part II - Reaction of pyridine dibromide

Preparation of pyridine dibromide in acetonitrile

Bromine (15.98 gm., O.lM) wa.s added by means of a dropping tunnel over a period of 30 minutes to 7.9 gm. of freshly-distilled p,yri dine (O.lM) which was dissolved in 25 ml. of acetonitrile. During the addition of bromine the solution turned deep red. When ail the bromine had been added, the mixture was heated very gently with a Glascol mantle; the reaction became so strongly exothermic that it bad to be cooled with an ice water bath. The mixture turned into a dark brown viscous liquid wb.ich was poured into 150 ml. of distilled water. Immediately orange red crystals of pyridine perbromide formed in solution. The pyridine perbromide could not be recrystallized. The yield was 7.5 gm., 31% of the theoretical m.p. 61-62° and the product decomposed a!ter a few hours with an evolution of bromine turning into a hard, dark-brown solid mass.

Preparation of pyridine dibromide in carbon tetrachloride

Freshly-distilled pyridine (O.lM) was dissolved in 25 ml. of redistilled carbon tetrachloride; to this solution 15.9 gm. bromine (O.lM) was added dropwise in fifteen minutes. During the addition of bromine onlT a few degrees rise in temperature was noted. The precipitated pyridine dibromide was filtered, washed with carbon tetrachloride and dried in a desiccator. The yield was 10.1 gm., 40% of the theoretical, m.p. 63-64°; it decomposed in fifteen hours.

Reaction of BYtidine dibromide with aniline

I. To a solution of 10 gm. of pyridine dibromide in 30 ml. of acetonitrile, 7.4 gm. of freshly-distilled aniline was added dropwise with stirring. The reaction was exothermic and the solution turned a very dark brown colour. Pink-coloured aniline hydrobromide was precip itated. The mixture was cooled in an ice-water bath and the pink crystals were filtered out. The yield was 3.9 gm. 66.

The colour of the pyridine dibromide disappeared around 200° • Three cr,ystallizations from acetic acid gave an almost colourless product of m.p. 283-284• (corrected); reported m.p. 285•. To the black filtrate, 50 ml. of distilled water was added. The precipitated black semi-solid mass dissolved in 20 ml. of methanol.

Addition of 40 ml. of distilled water caused the precipitation of a bro~ black mass; this mass was recrystallized three times from a water methanol mixture. Long colourless needles of 2,4,6-tribromoaniline were collected. Yield 1.1 gm., m.p. observed 121•, reported 119-120°. A sodium fusion test showed the presence of bromine and nitrogen.

II. Ten gm. of pyridine dibromide was diluted with JO ml. of acetonitrile; the solution was heated very gently with a Glascol mantle until bo iling started. Then it was cooled in an ice-water bath. To this black solution, 7.4 gm. of freshly-distilled aniline was added dropwise with stirring. The reaction was exothermic and the mixture became viscous. One point two gra.ms of almost colourless aniline bydrobromide was collected. The black acetonitrile layer was separated from the viscous product and 40 ml. water was added. The precipitated black mass was dissolved in methanol, precipitated again with wat er, and was recrystall ized three times from a water-methanol mixture. Colourless 2,4,6-tri bromoaniline was collected, m.p. 119-120°, reported m.p. 119-120°. Derivatives of 2,4,6-tribromoaniline 2,4,6-Tribromoacetanilide

2,4,6-Tribromoaniline (0.3 gm.) was dissolved in 10 ml. of acetic anhydride and two drops of concentrated sulphuric acid were added. Alter 20 minutes the reaction mixture was poured into an excess of war.m water and cooled in an ice-water bath. The precipitated anilide was filtered off, washed with water and dried. Two recrystallizations from ethanol gave a colourless cry stalline material, m.p. observed 232-232.5°, reported 232°.

2,4,6-Tribromobenzanilide

About 0.3 gm. of the 2,4,6-tribromoaniline was added to a solution of 0.5 ml. of benzoyl chloride in 10 ml. of dry benzene. The mixture was boiled under refiux for 20 minutes and allowed to cool.

After washing tœ benzene solution with 5 ml. of 2% sodium hydroxide, 5 ml. of 2% hydrochloric acid and 5 ml. of distilled water, the benzene was evaporated on a steam bath. Two recrystallizations of the above residue from dilute ethanol gave colourless crystals, m.p. observed 198-199°, reported 198°.

2,4,6-Tribromoformanilide

2,4,6-Tribromoaniline (0.5 gm.) in 6 ml. of formic acid (90%) was refiuxed for a period of twenty minutes. To the hot solution, 10 ml. 68. of distilled water was added and the mixture was cooled in an ice-water bath. The precipitated derivative was recrystallized three times from a 1:1 mixture or dr,y benzene and petroleum ether (b.p. 100-120°); m.p. observed 221.5°, reported 221.5°.

Infrared absorption spectra determinations

I. Apœratus and Materials

The Perkin-Elmer, Mbdel 21, double beam spectrophotameter equipped with sodium chloride prism was used. The spectra were taken in potassium bromide, infrared quality, obtained from the Harshaw Chemical Co., Cleve land, Ohio, u.s.A.

II. Spectroscopie techniques

The potassium bromide pellets were prepared as follows: about

0.5-1 mg. of the substance and approximately 0.4 gm. of potassium bromide, were placed with four small steel balls in a one ml. glass tube provided with a ground glass stopper. The mixture was ground for 3 minutes by a Perkin-Elmer vibrator. It was then pressed under 20,000 lbs./sq. in. for two minutes in a Perkin-Elmer pellet die.

In the case of liquids, dises of sodium chloride were used; they were polished with aluminium oxide suspended in absolute alcohol. Spectra of liquids were taken from samples put between two sodium chloride plates. The determination of spectra was carried out with the following 69.

setting of the instrument: resolution 927, response 1, gain 5.5, speed 5.5 and suppression O. The recordi.ng scale was 100 cm. -1; cm. for the range 3800-2000 cm. -1 , and

100 cm. -1;4 cm. for the range 2000-600 cm. -1 • The following scale in intensities was useda very weak (vw), weak (w), medium (m), strong (s), very strong (vs), shoulder (sh). 70.

TABLE I Positions of Absorption Maxima in the Infrared Spectra of N-substituted Trich1oroacetamidines

A = N-methy1trich1oroacetamidine B = N-ethy1trich1oroacetamidine C = N-pheny1trich1oroacetamidine D = N-benzy1trich1oroacetamidine

A B c D a. N-H and :N-H 3485m 3470vs 3480s 3340vs 3340vs 3370vs 3335ms 3310vs *Also C-H (aromatic) 3270vs stretching vibrations 3200(sh) 3160w 3205s 3050w 3050w *3030w 3030s b. CH and CH symm. and 2960w 2985vs 2970(sh) 3 2 asymm. stretching vibrations 2910w 2940ms 2870vw 2875m 2810 sh (sh) c. N-H and C=N deformation 1672s 1662s 1680vs vibrations 1640vs 1640vs 1660vs 1630vs 1627vs 1635vs d. **Aromatic ring vibrations **1595vs **1605vB i:-*1585vs e. Amidine II vibrations 1525s 1532s 1542 sh 1543s 1515vs f. CH asymm. and symm. band; 14B2m i~-*1485s 3 **1496s CH2 scissor vibrations 1465w 1463m 1445w 1452s 1448w 1452s l417s 1425m 1378ms 1365s 71.

TABLE I (continued)

A B c D g. C-N stretching vibrations l357s l340s l335s l315s l315vs l280vs skeletal vibrations 1274 1237m 1205s 1177rns l165vs 1170w 1170vs 1152vs ll45vs 1157vw l088ms 1070m 1080w l045vs l052vs 1063ms l022w l030m h. C-H band lOOBw 998w l008s 985w skeletal vibrations 948m 953m 915w 900s 912ms 917w 860s 882w C-H aromatic band 845ms 820vs 820vs 828vs C-Cl in cc1 stretching 3 vibrations 806s 806vs fA-C-H ar. monsubst. 785vs 782vs 782vs 780s W76üm W742s

710w 700m 705s 682w W688s

C-Cl stretch 675w 660s 665 sh 646m 640s 72.

SUMMARY AND CONTRIBUTIONS TO KNOWLEDGE

1. It was found that trichloroacetonitrile reacts with primary and secondary aliphatic, aromatic and heterocyclic amines at room temperature in the absence of catalysts, even in dilute water or alcohol solutions.

The reaction involves the addition of amine across the triple bond of the nitrile group to form N-substituted trichloroacetamidines.

2. N-phenyltrichloroacetamidine was prepared by a new route, from trichloroacetonitrile and aniline at room temperature. The yield was 90% and the reaction was carried out with the most favourable economie conditions.

3. The synthesis of the N-methyltrichloroacetamidine and N-ethyltrichloroacetamidine has been achieved in high yields by reaction of methylamine and ethylamine in water solutions with trichloroacetonitrile at room temperature. The two cornpounds were characterized by conversion to their salts with hydrochloric and picric acids.

N-benzyltrichloroacetarnidine was synthesized by this procedure.

From the reaction between trichloroacetonitrile and hydrazine hydrate hydrazine monohydrochloride was isolated; the formation of a yellow product was observed.

6. Attempts to prepare N-methyl- and N-ethyltrichloroacetamidines 73. from the hydrochloride salts of the methyl- and ethylamines and trichloroacetonitrile at room temperature failed; the reactants were recovered almost quantitatively unchanged, the observed unreactivity being explained.

7. A mechanism based on the chemical evidence obtained in this work has been proposed.

8. A second absorption band in the infrared spectra at 1520 ~ 10 -1 cm. was recorded. Characterization of this band as amidine II band for the open-chain N-substituted amidines has been suggested.

9. During this work a form of dermatitis was noted which developed when the skin came in contact with the liquida or solutions of the prepared N-substituted trichloroacetamidines.

10. The reactions between pyridine dibromide and aniline were investigated and the main products were isolated. It was found that pyridine dibromide brominates aniline in 2, 4 and 6 positions. 74.

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