?PO POPE AND GIBBON THE ALKALOIDAL SALTS OF

LXX I X . - The A lkal oida I Salts of Ph eny Emeth y I- phosphinic Acid.

By WILLIAM J A C K S O N POPE and CHARLES STANLEY GIBSON. MEISENHEIYER and Lichtenstadt (Ber., 1911, 44, 356) have recently succeeded in resolving phenylmethylethylphosphine oxide,

into optically active components by Pope and Peachey’s method (Trans., 1898, 73, 893); 3ipping and his pupils (Trans., 1909, 95, 1993; 1911, 99, 626) have also obtained strong evidence indicating that asymmetric organic derivatives of phosphoric acid are also resolvable by crystallisation with optically active bases. It appeared

CJ%(C,H,) (W%)PO,

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PHEN Y LMETHY LPHOSPHT NIC ACID. '741

theref ore desirable to attempt the resolution of some asymmetric derivative of phosphinic acid, and for this reason we have en- deavoured to separate phenylmethylphosphinic acid,

CH,( C,H,) P : O( OH), in to optically active components by crystallisation with optically active alkaloids. We have been unable to effect such a resolution, and, inasmuch as we have prepared a number of well crystallised salts of the acid with optically active bases, a considerable amount of evidence, negative in character, is now available, indicating that phenylmethylphosphinic acid is not resolvable into optically active components. The only suggestion which we can at present offer in explanation of this is the possibility that the acid in question may be readily converted into the ortho-form, CH,(C,H,)P(OH), even when present as a salt.

YJLenylmethylphosph.i?zic A cid.

This acid was prepared by a slight modification of the process given by Michaelis ( A n d e n , 1896, 293, 220), which consists in heating phenyldipiperidylmethylphosphonium hydroxide a t 150° for

.three to four hours, and evaporating the residue with ammonia on the water-bath until the solution is free from ammonia,; after filtration the silver salt is obtained as a voluminous, white precipi- tate by addition of silver nitrate, and, after filtration, is accurately precipitated with hydrochloric acid. The filtrate €rom the silver chloride yields the free acid on evaporation on the water-bath; a 75 per cent. yield of pure, crystalline phenylmethylphosphinic acid, melting a t 133-134O, is thus obtained.

I-M en thylamane Phenylmet hytphosphinut c, CH,( C,n,) P02H,C,,H,,* NH,.

This salt was obtained as a white, powdery mass on evaporating a benzene solution of corresponding quantities of 1-menthylamine and phenylmethylphosphinic acid to dryness ; after crystallisation from a mixture of dry acetone and ethyl acetate, the salt was separated into six fractions by crystallisation from ethyl acetate containing a little alcohol. The fractions form long, colourless, feathery needles, melting at 188-189O, are very soluble in water or alcohol, much less so in ethyl acetate, and sparingly soluble in acetone :

0.1046 gave 0,2516 GO, and 0-0934 q0. C= 65.60; H =9.99.

That no resolution has been effected is shown by comparison of C,,H,O,NP requires C= 65.52 ; €I = 9-71 per cent,

the rotation constants of the first and last of the six fractions.

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742 'POPE AND GIBSON: THE ALKALOIDAL SALTS OF

Fractiolt 1.

0.2376 Gram, made up to 30 C.C. with water at 15O. 1=4 dcm. Hggreex . H g y e n o w . Nayellow.

a ............... - 0.83" - 0.73" - 0.71' [a] ............ 26.2 23'0 22 '4 [MI ............ 81 *6 71 '7 69.8

Rotatory dispersions : Hggreell/X\Tayeiiow = 1 '169 ; Hgy;pellow/Nayellow = 1 W3.

Fraction 6.

0.2486 Gram, made up to 30 C.C. with water at 1 5 O . 1=4 dcm. a ............... - 0.85" - 0.76" - 0.74" [a] , ............ 26-2 22.9 22.3

Rotatory dispersions : Hggreen/Nayeiiow = I *I76 ; Hgyellow/N8yallow = 1.027.

Confirmation of the conclusion that no resolution had been effected was obtained by determining the rotation constants in aqueous solutions of equivalent concentrations of the Z-menthylamine hydro- chloride used; the values obtained were [aJD -36'4O and [MID - 69'7O. The latter value is experimentally identical with the corresponding values obtained €or the two fractions of salt.

[MI ............ 81 *7 71 '4 69 *5

Cinchomhe Yhe?tylnzethyZphosphinate, CH,( C6H,)Y0,H,Cl,H,0N2,2H20.

On evaporating equivalent quantities of the acid and the alkaloid in alcoholic solution 011 the water-bath, the above salt rapidly crystallises ; after eliminating excess of either component by crystal- lisation from ethyl acetate the salt was resolved into fractions by twenty-six crystallisations from this solvent. The extreme fractions were then again crystallised from water, and thus obtained in small, colourless needles ; both fractions appeared identical, but the melting points were not sharp. This was traced $0 the presence of water of crystallisation, and the highest melting point observed was 170-172O. The salt is very soluble in alcohol or hot benzene, and sparingly so in ethyl acetate:

0.1253 gave 0.2952 CO, and 0*0850 H20. 0.4718 lost 0.0342 a t 103-llOo.

C = 64.09 ; H = 7.54. H20=7.25.

C,H,,0,N2P,2H20 requires C = 64.31 ; H = 7.26 ; q0 = 7.40 per cent.

The following rotatory-power determinations of the first and last fractions were made :

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PEENYLMETHYLPHOYPHINIC ACID. 743

First Fraction.

0.2630 Gram, made up to 30 C.C. with water a t 17O. 1=4 dcm.

Hggreen. Hgyellow. Nayellow. u ............... + 5'30" f 4.63" + 4-45" [a] ............ 151 -0 132.0 126 9 [MI ............ 735 642 617

Rotatory dispersions : Hggreen/Nayciiow = 1.191 ; Hgyel~ow/Nayt?llow= 1.040.

Last Fraction.

0.2610 Gram, made up to 30 C.C. with water at 17O. a ............... + 5-24' + 4-58' + 4-40" [a] ............ 150% 131.5 126.5 [MI ............ 732 640 615

Rotatory dispersions : Hggrce,,//Nayellow = 1 *190 ; Hgyeiiow/Nayeilow = 1 -040.

It is clear that no resolution has been effected, and the molecular rotatory powers given may be taken as those of the cinchonine ion.

Cin chonadine Phenylm e thylphosphim t c, CH,( C$&)P02B,C,H&N ,4H@ -

This salt was obtained as a crystalline residue on evaporating an alcoholic solution of its components on the water-bath. After systematic fractionation by twenty recrystallisations from ethyl acetate and from water, no resolution appeared to have occurred. The salt crystallises from water in beautiful, colourless prisms, melting a t 154O; it is very soluble in alcohol, benzene, or boiling water, and sparingly so in ethyl acetate or cold water :

0'1212gave 0.2672 CO, and 0*0900 H,O. 0.5443 lost 0.0'736 at llOo.

C=60-12; H=8*31. H20=13'52.

C26E,,03N,P,4H,0 requires C = 59.87 ; H = 8-49 ; H,O = 13.79 per cent.

The rotatory powers of the extreme fractions were determined in alcoholic solution at 17'5O.

First Fraction.

0 2650 Grams in 30 C.C. 1=4 dcm.

Hggreen- Hgyollo w- Nayellow, u ............... - 3.01' - 2'60" - 2'49" [a] ............ 85 '1 73-6 70 -5 [MI ............ 444 384 368

Rotatory dispersions : Hggreen/Nayeiiow = 1'207 ; Hgy6110w/Nayellow = 1 '044.

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744 POPE AND UIR30N: THE ACRAT,OIDAT, SALTS OF

Last Praction.

0.2746 Gram in 30 C.C. 1=4 dcm. a ............... - 3'12" - 2-69" - 2.58" [u] ............ 85.4 73.5 70.5 [MI ............ 446 384 368

Rotatory dispersions : Hggreen/Nayellow = 1 *211 ; Hgyellow/Nayellow = 1943.

Quinine Ph en y lm e thy 1 p hos phina t e, CH,(C,H, )P0,H,CmH,0,N2,4H,0.

On evaporating an alcoholic solution of corresponding quantities of the alkaloid and acid to dryness, this salt remains as a bulky, white, crystalline powder ; when crystallised from ethyl acetate con- taining a little alcohol, the salt was obtained in fractions which differed in melting point and in rotatory power, but these differences were ultimately traced to the absorption of atmospheric moisture by the various fractions. On prolonged fractional crystallisation from water the material was separated into a number of fractions which proved to be identical; the hydrated salt commences to melt a t 8 5 O , but the anhydrous salt melts a t 164-166O. It is readily soluble in alcohol or in hot ethyl acetate and water, but dissolves sparingly in cold water:

0.1042 gave 0.2238 CO, and 0.0720 H,O. 0.5392 lost 0.0714 a t l l O o .

C = 58.57 ; H = 7.73. H,O=13*24.

C,7H330,NzP,4H,0 requires C = 58.65 ; H = 7-48 ; H,O=13.05 per cent.

The following determinations of the rotation constants of extreme fractions were made in alcoholic solutions at 15O in 4-dcm. tubes :

First Fraction.

0.2032 Gram in 30 C.C.

Hggreen. H gyello w - Nayellow. a ............... - 3'83" - 3.28" -- 3.07" [u] ............ 141.4 121-1 113.3 [A$] ............ 781 669 62.5

Rotatory dispersions : HgpeeJNayellow = 1 '248 ; Hgye~~ow/Naye~~ow = 1.068.

Last Fraction.

0.1980 Gram in 30 C.C.

[a] ............ 3 40 '9 120'8 11 3.6 [MI ............ -' i 7 8 667 627

Rotatory dispersions : Hgpeen/Nayeiiow = 1 240 ; Hgye11ow]Napllow= 1 '063,

a ............... - 3.72" - 3.19" - 3.00" *,lP

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PHENPLMETHYLPHOSPHIXIC ACID. 745

The practical identity of the rotation constants for the first and final fractions again indicates that no resolution has been effected. On attempting to form a salt between phenylmethylphosphinic

acid and Z-tetrahydroquinaldine, the acid was found to crystallise unchanged from the base.

Hydroxyhydrindamine Ph en ylmcthylphosphimt c,

CH,(C,H,)PO,H,C,H,<~H~~H~.

When a solution of corresponding amounts of externally compen- sated hydroxyhydrindamine (Pope and Read, Trans., 1911, 99, 20'19) and the phosphinic acid in alcohol is evaporated, a crystalline salt separates, and is readily purified by crystallisation from alcohol. It forms light, silky needles, which decompose a t about 170° without melting, and is readily soluble in alcohol, but dissolves sparingly in ethyl acetate or acetone:

0.1476 gave 0.3424 GO, and 0.0906 H20.

For comparison with the above fully racemic salt, the correspond-

C = 63-25 ; H = 6.87. Ci16H2003NP requires C = 62.91 ; H = 6.61 per cent.

ing salt of I-hydroxyhydrindamine was prepared,

1-Hydrozyhydrindamine Ph enylm e t hylphosphinat e.

This salt crystallises on evaporating an alcoholic solution of its components; it was separated into four fractions by prolonged crystallisation from ethyl acetate containing a little alcohol, and is thus obtained in long, silky needles, which begin to decompose a t 1T5O, and subsequently melt. The *alt is very soluble in alcohol or water, but almost insoluble in ethyl acetate :

0.1176 gave 0.2705 CO, and 0.0686 H,O.

The following determinations of the rotation constants were made on the extreme fractions in aqueous solutions a t 17O in 4-dcm. tubes :

C=62*77; H=6.53. C16H,,0,NP requires C = 62.91 ; H = 6'61 per cent.

First Pra c t ion.

0.2546 Gram in 30 C.C.

Hggreen. Hgyellow. Nayelion.

a ............... - 0.80" - 0.69" - 0.67" rUj ............ 25-6 20 '3 19.7 [MI ............ 71.9 62.6 60 '2

Rotatory dispersions : Hgneen/Nayei iow = 1 -194 ; Hgyeitow/Nayeiiow = 1 '030.

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746 GRAHAM: THE OPTICAL ACTIVITY OF

Last Fraction.

0.2492 Gram in 30 C.C.

[a] ............ 23 -5 20.2 19-6

Rotatory dispersions : H g m e ~ / N a ~ e ~ ~ ~ , w = 1.201 ; H g y e l l ~ w / N a y e ~ l ~ w = 1.031.

a ............... - 0.78" - 0.67" - 0.65"

[MI ............ 71.6 61-5 59 *7

It is thus obvious that the acid is not resolved by crystallisation with Z-h ydrox yh y dr indamine.

THE CHEMICAL LABORATORY, THE UNIVERSITY,

CAMBRIDQE.

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