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THE ACTION OF THE GRIGNARD REAGENT, ETC. 251

XXX.---The Action of the Gy-ignard Reagent on Published on 01 January 1921. Downloaded by Temple University 27/10/2014 17:49:46. certain Nitric Esters. By HARRYHEPWORTH. ALTHOUGHthe action of the Grignard reagent on numerous types of organic compounds has been investigated, yet, with the single exception of the interaction of magnesium methyl iodide and methyl nitrate (Moureu, Compt. rend., 1901, 132, 837), no investigations have been carried out on the action of this important reagent on the nitric esters. Moureu (Zoc. cit .) investigated the actiou of the Grignard reagent on certain nitroparaffins and esters of nitrous acid, and found that both classes of compounds gave rise to P&dialkylhydroxylamines. Bewad (Ber., 1907, 40, 3065) studied the action of magnesium or zinc alkyl iodides on esters of nitrous acid and on nitroparaffins. It was found that in the preparation of /3@-dialkylhydroxylamines, View Article Online

252 HEPWORTH: THE ACTION OF THE

the zinc alkyl usually employed (idem, J. Russ. Phys. Chem. SOC.,1900, 32, 420, 455) can be replaced advantageously by zinc alkyl iodides or magnesium alkyl iodides when the esters of nitrous acid are used, but not in the case of nitroparaffins. With the latter, the reaction follows two courses, in both cases the final pro- duct being a Dfl-dialkylhydroxylamine, the one containing one alkyl group derived from the magnesium alkyl haloid employed, the other containing two. From a consideration of the three possible structural formula: for the esters of nitric acid, it is evident that, with the Grignard RO*N

reagent, a considerable number of reaction products can be theoretically anticipated. If Bruhl’s formula (the first) is correct, then it might be possible to obtain selective action of the Grignard reagent on one of the oxygen atoms attached to nitrogen. At the same time, primary selective action of the Grignard reagent with aromatic nitro-compounds, in which the nitro-group cannot possibly have a configuration as in the first formula, has been shown to take place by Odd0 (Atti R. Accad. Lincei, 1904, [v], 13, ii, 220), and confirmed by the author (T., 1920, 117, 1004). In ail earlier communication (T.,1919, 115, l203), the author has shown that, in certain cases, selective action of the Grignard reagent can be easily realised by the application of the method of Kipping and Davies (T., 1911, 99, 296). In this method, a mix- ture of the substance, together with alkyl haloid, diluted with ether, is added drop by drop to well-cooled ether containing magnesium powder, the rate of addition of magnesium being such as to keep the latter in excess throughout the reaction. Published on 01 January 1921. Downloaded by Temple University 27/10/2014 17:49:46. In this investigation, the action of magnesium methyl iodide and magnesium ethyl bromide on ethyl nitrate, ethylene glycol dinitrate, glyceryl trinitrate (nitroglycerol), and the tetranitro- derivative of pentaerythritol has been investigated. It was found that all these nitrates prevented the initial formation of Grignard compounds. This observation was repeatedly confirmed with small quantities of these nitric esters dried over phosphoric oxide for several days, and also with samples which had been first treated with a sniall quantity of a solution of the Grignard compound and then decanted. In other experiments, the formation of the Grignard compound was first started by the addition of a little alkyl haloid, and then the mixture of nitric ester and alkyl haloid was added, drop by drop, to the magnesium, but the vigorous reaction which was in progress soon ceased after a small portion of the nitric ester had been added, and could not be made to start View Article Online

GRIBNARD REAGENT ON CERTAIN NITRIC ESTERS. 253

again. The only other observation of this type appears to be that recorded by Kipping and Davies (T., 1911, 99, 296), who found that acetone prevented the interaction of magnesium and benzyl chloride or ethyl bromide. It was therefore necessary to abandon this method of procedure and to prepare the Grignard reagent separately. Experiments were carried out under a variety of conditions, in which the nitric ester was added to the Grignard reagent and vice versa, and in which the reaction vessel was cooled to various temperatures from zero to -15O. In every case, the principal products of reaction were found to be either PB-dimethylhydroxylamine or PP-diethyl- hydroxylamine, whichever of the four nitric esters was employed. Minute traces of neutral products were formed, but the quantities obtained were not sufficient to admit of detailed examination. The best results were obtained when three to four molecular proportions of the Grignard reagent to each *O*NO, group were employed. No selective action of the Grignard reagent was observed, and the course of the reaction, in the case of all four esters, may be simply represented as follows :

RO*NgO0 -+2MgR’X+ R0.N-R/OMgx +MgR’X-+ R0.N-R/MFx h>OMgX I \R’ OMgX

2: R0.N-R‘/H + R*OH+NR’R‘*OH I \R’ OH (IV.) Published on 01 January 1921. Downloaded by Temple University 27/10/2014 17:49:46. Other modes of reaction might be postulated, but these demand selective action of the Grignard reagent with one of the oxygen atoms of the nitric ester, and as such selective action was not observed, it appears better to postulate the reaction as above. In some experiments the formation of a small quantity of a secondary base was observed. This is probably formed by the further action of the Grignard reagent on compound 111.

/Mgx +MgR’X+ RO*N\R/M!X -++I120 RO*N/H? -R Ro*F:’ I R’ pw OMgX MgX (111.) (V. 1 (VI.) -ROH -+ ::>NH (VII.) View Article Online

254 TiIEPWORTII: THE ACTION OF THE

Bewad (Uer., 1907, 40, 3065) observed that nitric oxide was evolved, and secondary bases, as well as /3@-dialkylhydroxylaniines, formed, on adding isoamyl nitrite to zinc ethyl iodide, and attributed both phenomena to a process of oxidation. It is difficult to conceive how PP-diethylhydroxylamine could be directly oxidised to diethylamine. In the course of the experi- ments described in this paper, it was observed that some nitric oxide was evolved when the flask was allowed to become hot during the decomposition of the product with water. The evolution of nitric oxide became more pronounced when the reaction product was distilled in steam, particularly at the early stages of distilla- tion, or even when it was heated on the water-bath before the addition of water, and it is suggested that the nitric oxide is derived froin the decomposition of the products I11 and V. Exhaustive attempts were therefore made to isolate the bases by repeatedly extracting with ether, but even in those cases in which a very small quantity of water was used for the decomposi- tion of the reaction product, eighteen to twenty extractions -did not suffice to remove the whole of the bases present, so that, in spite of decomposition with evolution of nitric oxide during the early stages of the distillation with steam, the latter method of isolating the bases was more expedient and generally more satisfactory than extraction with ether.

E XP ER I ME N TA L. .I ctim o/ Muynesawn Methyl Iodide on Ethpll fiitrute. I’reptcratiotL of Ethyl Nitrate.-The ethyl nitrate used in these experiments was prepared by a slight modification of the method Published on 01 January 1921. Downloaded by Temple University 27/10/2014 17:49:46. of Lossen (Arm. Suppk., 1868, 6, 220). Nitric acid (D 1-4) of very low nitrous acid content was boiled for fifteen minutes with 1 per cent. of its weight of carbamide nitrate. After cooling, 100 grams oE the acid were cautiously mixed with 100 C.C. of absolute alcohol in a retort connected with a condenser, and the contents of the retort evaporated to one-half of the volume on a sand-bath. A freshly prepared mixture of 100 grams of purified nitric acid and 50 C.C.of absolute alcohol was added drop by drop to the heated retort. Some considerable difficulty was encountered through this mixture becoming warm and fuming before it could be added, and a considerable improvement was effected by interposing a short water-condenser between the funnel and ths retort. Distillation was continued until about two-thirds of the contents of the retort had passed over. The distillate was washed several times with water, dried over calcium chloride, and distilled from a salt-water View Article Online

GIRIGNARI) REAGENT ON CERTAIN NITRIC: ESTERS. 266

bath. The ethyl nitrate boiled constantly at 86O, and was kept over a little anhydrous sodium sulphate until required for use. Reaction with Magnesium Methyl Iodide.-A mixture of 18.2 grams of ethyl nitrate and 50 C.C. of dry ether was added drop by drop to an ice-colld solution of magnesium methyl iodide, pre- pared in the usual way from 17.5 grams (34 mols.) of magnesium, 102 grams (3+ mols.) of methyl iodide, and 250 C.C. of dry ether contained in a flask attached to a long reflux condenser. The ethyl nitrate-ether mixture was added during one hour, and reac- tion was just perceptible. After about two-thirds of the mixture had been added, the contents of the flask separated into two layers, the lower being of a green, oily consistence, andl the upper dis- tinctly milky. The flask was then removed from the ice and kept at the ordinary temperature for twenty-four hours, after which it was again cooled in ice, and the contents cautiously decomposed with 50 C.C. of cold' water. With this quantity of water, the magnesium hydroxide separated as a stiff paste. During the decom- position, some nitric oxide was evolved, which was detected as nitrogen peroxide at the top of the condenser by the instantaneous action on a moistened starch--potassium iodide paper. The contents of the flask were then distilled in steam until the condensed water no longer showed an alkaline reaction. The base was collected in hydrochloric acid. The solution, after being con- centrated to a small bulk, was evaporated to dryness in a vacuum over sulphuric acild. A small portion of the hydrochloride was recrystallised from a mixture of alcohol and ether, from which it separated in long needles. The compound softened at 92O and melted at 94-96O (Found : C1= 37.12, 37-08. NMe2-OH,HC1 requires C1= 36-41 Published on 01 January 1921. Downloaded by Temple University 27/10/2014 17:49:46. per cent.). The hydrochloride therefore appears to be con- taminated with the hydrochloride of some base of lower molecular weight. Isolation of the base .-The crude hydrochloride was treated with an excess of a very concentrated solution of potassium hydroxide in a small flask attached to a condenser, and the base dis- tilledl into a receiver cooled in ice. A volatile, uncondensed base having an ammoniacal, fishy odour passed over first, then the temperature quickly rose to 90°, and a readily condensible base was collected, the greater portion at 93-95O, but the distillation was continued up to looo. The liquid in the receiver, which was present in two layers, was shaken with 100 C.C.of ether and dried over barium oxide. On distillation, about 8 grams of crude pro- duct passed over at 91-960, from which, on redistillation, 6 grams of a base boiling at 94-5-95-5O (cwr.) were Qbtainedi. The com- View Article Online

256 HEPWORTH: THE ACTION OF THE

plete removal of the ether used for solution presented some difficulty. The base had an unpleasant, ammoniacal odour. It quickly reduced Fehling’s solution, especially on gently warming, and reduced an ammoniacal solution of silver nitrate instantly in the cold. It had D15 0*8877, and was readily soluble in water, forming a solution with a strongly alkaline reaction (Found: N=22.78, 22.82. C,H,ON requires N = 22.95 per cent.). The base was reduced by tin and hydrochloric acid to dimethyl- amine, which was identified a5 its hydrochloride (Found: C1= 43.48; N=17.09. Calc.: C1=43*56; N=17*18 per cent.). The original base therefore appears to be PP-dimethylhydroxyl- amine, as was suggested by Moureu (Zoc. cit.). PP-Uimethylhydroxylami~e hytlrocliloride crystallises from alcohol or from a mixture of ether and alcohol in small, elongated, laminated plates melting at 102O (corr.). When crystallisation proceeds very slowly, the crystals are considerably more elongated than those deposited quickly. Its aqueous solution is acidic. It is readily soluble in ethyl or methyl alcohol, but almost insoluble in all other common organic solvents. ~P-Dimeth.ylhydroxy1amineoxalate is most readily prepared by the addition of a clear, ethereal solution of anhydrous oxalic acid to an ethereal solution of two equivalents of the base. After keeping for two hours, the precipitated salt is thoroughly washed with dry ether and recrystallised from anhydrous methyl alcohol, from which it is deposited in small, hexagonal prisms melting at 154:. It is readily soluble in water, warm ethyl or methyl alcohol, sparingly so in hot acetone, and almost insoluble in all other common organic solvents (Found : N = 13-16, 13.14. C,H,,O,N,

Published on 01 January 1921. Downloaded by Temple University 27/10/2014 17:49:46. requires N = 13.20 per cent,). This experiment indicated that traces of a base other than PP-dimethylhydroxylamine were formed in the reaction, and further experiments were carried out in which 6 molecular pro- portions of magnesium methyl iodide were employed. The pro- cedure was as described above, except that the volatile base first coming over on distillation was collected in (dilute hydrochloric acid. By evaporation in a vacuum over sulphuric acid, about half a gram of crude dimethylamine hydrochloride was obtained. After two crystallisations from a mixture of ether and alcohol, the salt melted at 170°, and the melting point was not appreciably altered on mixing with a trace of pure dimethylamine hydrochloride. In this case, as before, the main product of the reaction was PP-dimethylhydroxylamine. Experiments were carried out in which the products of reaction, View Article Online

GRIGNARD REAGENT ON CERTAIN NITRIC ESTERS. 267

after decomposition with water, were extracted eighteen to twenty times with ether, and the base then converted into the hydro- chloride. The yield in this case was not so satisfactory on account of the difficulty of extracting the whole of the base with ether,

Action of Magnesium Ethyl Bromide on Ethyl Nitrate.

A solution containing 18.2 grams of ethyl nitrate in 60 C.C. of dry ether was slowly added to magnesium ethyl bromide, prepared from 17.5 grams (34 mols.) of magnesium, 80 grams (34 mols.) of ethyl bromide, and 250 C.C. of ether, the flask being cooled to -3O. The reaction was very vigorous, much more so than in the case of magnesium methyl iodide. After decomposition of the product with water (60 c.c.), the base was removed by distillation in steam, as in the previous experiment. The aqueous solution of the hydrochloride was con- centrated in the water-bath, and finally in a vacuum over sulphuric acid. The free base was obtained as before, and the presence ?f some base of lower molecular weight again indicated. The base (12 grams) boiled at 130-135O, with slight decom- position, reduced Fehling's solution on warming, and an ammoniacal solution of silver nitrate in the cold. The oxalate was prepared by adding anhydrous oxalic acid to an ethereal solution of the base until no further precipitation took place. After recrystallising from methyl alcohol, the salt melted at 137-138O. The melting point of BB-diethylhydroxylamine oxalate is 136-137O (Dunstan, T., 1899, 75, 793) or 138O (Wieland, Ber., 1903, 36, 2317). The hydrochloride was prepared by treating an ethereal solution Published on 01 January 1921. Downloaded by Temple University 27/10/2014 17:49:46. of the redistilled base with a solution of hydrogen chloride in the same solvent. The salt was extracted with a little water, and, after concentration of the aqueous solution in a vacuum over sulphuric acid, crystallised in long, colourless plates melting at 63-64O (Wieland, Eoc. cit.) (Found : C1= 27.98'. Calc. : C1= 28-22 per cent .). The base therefore appears to be BB-diethylhydroxylamine. By treating ethyl nitrate with 6 molecular proportions of mag- nesium ethyl bromide, a small quantity of a volatile base, which boiled at 55--58O, was obtained, the hydrochloride of which melted at 217O (the mixture with diethylamine hydrochloride melted at 217--217*5O), from which it was evident that diethylamine was formed in this reaction.

VOL. CXIS. K View Article Online

258 HEPWORTH: THE ACTION OF THE

Action of Magnesium Ethyl Bromide on Ethylene Glycol Dinitra t e.

Preparation of Ethylene Glycol Binitrate.-Thirty grams of ethylene glycol (b. p. 137--139O/90 mm.) were esterified with a mixture of nitric and sulphuric acids (HNO,= 40.00 ; H,SO, = 58.85 ; HNO, = 0.15 ; H,O = 1.00 per cent.) in a large beaker surrounded by a freezing mixture, the glycol being added at such a rate that the temperature was maintained at 10-12O. The ratio of acid to glycol was 7 to 1. Air stirring was continued for ten minutes after the glycol had been added, and the glycol dinitrate was then allowed to separate for thirty minutes, n:J accelerator being employed. After removing the mixed acid, the glycol dinitrate was washed with water at 25O, with sodium carbonate solution (1 per cent.), again with water, and, after filtration, dried in a partial vacuum over solid potassium hydroxide. It was thus obtained as a clear, mobile, faintly yellow oil (D12 1.480) (Found : N = 18-37, 18-41. Calc. : N = 18.42 per cent.). The yield was 55 grams. Reaction with Magnesium Ethyl Bromide and with Magnesium- Methyl Zodide.-A very vigorous reaction occurred when a mixture of 10 grams of ethylene glycol dinitrate and 30 C.C.of dry ether was added drop by drop during one hour to an ice-cold solution of mag- nesium ethyl bromide, prepared in the usual way from 12 grams (7 mols.) of magnesium and 54 grams (7 mols.) of ethyl bromide con- tained in a flask attached to a long reflux condenser. A greyish- white solid quickly separated, and the upper layer became adistinctly milky. After keeping at the ordinary temperature for twenty- four hours, the flask was again placed in ice, and its contents Published on 01 January 1921. Downloaded by Temple University 27/10/2014 17:49:46. cautiously decomposed with cold water (60 c.c.), some nitric oxide being thereby evolved. The base was then distilled in steam and purified, as in the previous experiments. Nine grams of a base, b. p. 132-137O, were Obtained, the identity of which with PP-diethylhydroxylamine was established by its conversion into the hydrochloride, m. p. 63-64O, and oxalate, m. p. 137-139O. After removal of the base, the ether contained a neutral pro- duct, the quantity of which, however, was too small for investigation. In a similar experiment, in which 10 grams of the glycol dinitrate were added to a solution of magnesium methyl iodide, prepared from 12 grams (7 mols.) of magnesium, 70 grams (7 mols.) of methyl iodide, and 250 C.C. of dry ether, 6 grams of ~&dimethylhydroxylamiiiewere obtained, the identity of the base View Article Online

QRIGNARD REAGENT OF CERTAIN NITRIC ESTBRS. 259

being established by the, b. p. and by its conversion into the hydro- chloride and the normal oxalate. The reaction of the glycol dinitrate with magnesium methyl iodide is much less violent than with magnesium ethyl bromide.

Action of Magnesium Ethyl Bromide and of Magnesium Methyl lodide on Glyceryl Trinitrate (Nitroglycerol).

Preparation of Glyceryl Trinitrate.-Thirty grams of glycerol were esterified, in the same manner as ethylene glycol. The pro- duct was stabilised by washing successively with water at 25O, 1 per cent. sodium carbonate solution, and water, and, after filtration and drying in a vacuum over solid potassium hydroxide, yielded 62 grams of glyceryl trinitrate having a faintly yellow colour (Found : N=18-48, 18.49. Calc. : N=18.51 per cent,). Reaction with Magnesium Ethyl Bromide and with Magnesium Methyl Iodide.-A mixture of 10 grams of glyceryl trinitrdte and 60 C.C. of dry ether was added drop by drop to an ice-cold solution of magnesium ethyl bromide, prepared from 12.5 grams (11 mols.) of magnesium, 57 grams (11 mols.) of ethyl bromide, and 250 C.C. of dry ether. Nine grams of BB-diethylhydroxylamine were isolated in the usual way. In a similar experiment with a solution of magnesium methyl iodide, prepared from 75 grams of methyl iodide and the same quantity of magnesium as before, 6 grams of PB-dimethylhydroxyl- amine were obtained from 10 grams of glyceryl trinitrate. The reaction with magnesium ethyl bromide was again observed to be much more vigorous than with magnesium methyl iodide. Published on 01 January 1921. Downloaded by Temple University 27/10/2014 17:49:46. Action of Magnesium Ethyl Bromide and of Magnesium Methyl Zodide on Pentaerythritol Tetranitrate. Pentaerythritol tetranitrate was prepared by Vignon and Gerin's method (Compt. rend., 1901, 133, 590). Eight grams of finely powdered pentaerythritol were added to 50 grams of nitric acid (97 per cent.) at Oo, the temperature being kept below 12O during the addition. At first the solution was clear, but the nitrate soon began to separate. The mixture was slowly added to 80 grams of concentrated sulphuric acid at Oo. After one hour, the product wa8 collected, washed with water, dissolved in acetone, and pre- cipitated with alcohol; it then melted at 138-139O (Found: N = 17.53 ; 17.60. Calc. : N = 17.72 per cent.). Pentaerythritol tetranitrate is almost insohble in ether. The solution obtained by shaking 1 gram of the substance with K2 View Article Online

260 HARDINQ: THE MELTING POINTS OF MIXWRES OF

1000 C.C. of dry ether for two to three hours was added to a solu- tion of magnesium ethyl bromide, prepared from 1.2 grams of magnesium (14 mols.), 5 grams (14 mols.) of ethyl bromide, and 30 C.C. of dry ether. A small quantity of base was obtained, and its identity with PB-diethylhydroxylamine established by con- version into the hydrochloride and the oxalate. In a similar manner, /3/3-dimethylhydroxylamine was obtained when magnesium methyl iodide was employed.

The author is indebted to the Research Committee of Messrs. Nobel’s Explosives Company, Ltd., anld particularly to Mr. Rintoul, for the facilities accorded him in carrying out this investigation.

THE RESEARCH LABORATORIES, AJXDEERFACTORY, STEVENSTON,N.B. [Received, December 28th, 1920.1 Published on 01 January 1921. Downloaded by Temple University 27/10/2014 17:49:46.