NOTES
Aug. 20, 1953
r:'
4079
white precipitate. The yellow liquid was concentrated on the steam-bath and formed a yellowish-white solid. Both the white precipitate and the residual solid obtained from the liquid portion of the reaction mixture were combined 2 +PClS+ [ ( C H a ) , si O ] ppcl and washed 6rst with dilute sodium hydroxide and then with water. The residual product was extracted with ether and the ether extract dried over anhydrous sodium sulfate. After removal of the ether, the remaining solid was recrystallized I11 Si(CH& from alcohol, yielding a colorless, crystalline product, m.p. (11) with potassium permanganate in aqueous and 259' (uncor.). The yield was 30%. in pyridine solution did not result in the formation Anal. Calcd. for CnHtoOPSia: Si, 17.0; P , 6.3. Found: Si, 17.4; P, 6.8. Bie-( p-trimethylsilylheny1)-phosphonic Acid fV).-Th e sodium hydrox3 -t POCh + [(CH&Si-],P+O 4- [ ( C H d a S i ~ l s < ~ H ide binedextract solid products from theofcomthe
[
IV Si(C%)a
reaction of p-trimethylsilylphenylmagnesium bromide and phosphorus oxychloride was acidified with dilute hydrochloric acid, resulting in a CO~Or~~S, crystalline Product, m.P. 213-214.5' (LIWX.). The yield was 15%. Anal. Calcd. for C1~Hn,OePSil:Si, 15.5; P, 8.6. Found: si, 16.6; p, 8.9. V
of the corresponding phosphine oxide. This result is not surprising in view of the well-known resistance of aromatic phosphines toward oxidation. p-Trimethylsilylphenylmagnesium bromide (I) when treated with phosphorus oxychloride yields NEW both the phosphine oxide (IV) as well as the di- G~~~~~ ELECTRICcoMPANY phosphonic acid (V) The procedure was essen- PITTSFIELD, MASS. tially that of Kosolapoff .z
.
Experimental
p-Trimethylsilylphenylmagnesiumbromide (I) was pre-
pared from 12e2 g. of magnesium turnings, 114.5 g* of pbromophenyltrimethylsilane and 550 cc. of anhydrous ether. The reaction was initiated by means of a small amount of ethylmagnesium bromide. Tris-( p-trimethylsilylpheny1)-phosphine(II). (A).-In a three-necked flask, equipped with stirrer, reflux condenser and dropping funnel, were placed 34.4 g. of phosphorus trichloride and 100 CC. of ether. Half of the above prepared Grignard solution was added gradually through a dropping funnel. Afterwards the mixture was refluxed for three hours. The inorganic precipitate was filtered off and washed with ether. The solvent was then removed from the filtrate. The weight of the residual material was 68.1 g, On s t a m k g in the refrigerator, crystals formed which were recrystallized from alcohol, yielding colorless needles, m.p. 95-96' (uncor.). B.-Half of the above described Grignard solution was added slowly to a solution of 52.1 g. of phosphorus pentachloride in 100 cc. of ether. The product was worked up in the same way as described in A. The residual material weighed 63 g. It was vacuum distilled. Tris-($-trimethylsilylpheny1)-phosphine (II) distilled at 112-117 a t 31 mm. It was recrystallized from alcohol, yielding colorless needles, m.p. 95-96' (uncot.). A mixed melting point taken with the products obtained by procedures A and B showed no depression, establishing thereby the identity of the two materials. The yields of the pure product ranged from 3545%. Anal. Calcd. for CnHNPSir: Si, 17.6; P, 6.5. Found: Si, 17.2; P, 6.8. In the above distillation, another fraction was isolated, distilling at 72' at 43 mm. as a colorless liquid. Anal. Calcd. for CaH&lPSiz: Si, 15.4; P, 8.5. Found: Si, 13.1; P, 8.9. While this compound evidently was not pure, it probably contained bis-(p-trimethylsilylphenyl)-chlorophosphine (111). The presence of chlorine was proven by means of a qualitative test. Tris-(p-Mmethylailylphenyl)-phosphine Oxide (IV).-pTrimethylsilylphenylmagnesiurn bromide, prepared from 57 g. of p-bromophenyltrimethylsilane,was added gradually to a solution Of 38 g. of P h m P h a s oxychloride in 300 CC. of ether which was brought to reflux before the addition. The reaction mixture was then r d u x e d for 16 h-. After cooling, the yellow liquid was decanted from the residual solid. The solid was hydrolyzed in ice-water forming a (1) a.M. Phnolopoff, TEU J O ~ A L M, , 2QM(19Ip).
Chemistry of Vitamin Ba. X. Some Homologs of the Vitamin Ba Group By DOROTHEA HE^, EILEENLuz, STANTON A. HARRISAND KARL FOLKERS RECEIVED APRIL22, 1953
An ethyl homolog of Pyridoxine, 2-ethyl-3hydroxy-4,5-bis-(hydroxymethyl)-pyridine,was reported previously.' Two higher homologs have been prepared: the corresponding and n-amYl derivatives. These compounds were synthesized in general by the sequence of reactions which was used for preparation of the ethyl homo!Og, the main difference being that Of the intermediates were not isolated. The compounds actually isolated are represented by the formulas I through v. CHaOCHnCOOCH:
> CH,(coN" CN
RCCH3CCHnOCHa
I1
0
I
CHIOCH:
"01 RON/OH N
AcaO
I1 CHzOCH:
3
OnN \ C N
R N/OH I11
Pd.Hs.HC1
Iv
rcHa
_____t
then "01 then HCI
HO \CHnOH
R N/
A, R = i-C,Hp B, R = n-CsHt~
V
2-Ethyl- 3 hydroxy 4,5 bis (hydroxymethy1)pyridine' was oxidized to 2-ethyl-3-hy~oxy4-formyl-5-hydroxymethylpyridine, which was isolated as the oxime VI. The latter was con(1) 9. A. E u r i m and A. N. Wilion, T B IJOURNAL, ~ 68,2626 (1941).
VOl. 75
NOTES
4080
Oxime of 2-Ethyl-3-hydroxy-4-formyl-5-hydroxymethylpyridine (VI).-2-Ethyl-3-hydroxy-4,5-bis-(hydroxymethy1)pyridine hydrochloride' (10.7 g:) was oxidized with manganese dioxide and sulfuric acid in a manner exactly analogous to the preparation of pyridoxal oxime.* The OCzHb yield of the oxime of 2-ethyl-3-hydroxy-4-formyl-5-hydroxyI methylpyridine was 4.8 g. (50%). After one recrystallizaH C -0 tion from water-alcohol and one from alcohol, the oxime CH=SOH melted a t 225-226". HO' \ --AH2 ITWq\ -CH201I .Inal. Calcd. for CgH12N203: C, 55.09; H , 6.17; S , 14.28. Found: C, 53.22; H , 6.00; N, 14.12. cI ~ J , ~ ~ c2tla\yq Monoethyl Acetal of 2-Ethyl-3-hydroxy-4-formyl-5-hydroxymethylpyridine Hydrochloride (VI1j .-Conversion of VI \'I I Y .4 g. of the oxime of 2-ethyl-3-hydroxy-4-formyl-5-hytlroxpmethylpJ.ridine (\.I) to the corresponding monoethyl Experimental4 acetal u-as carried out in the manner previously described The reactions carried out for the preparations of 2 4 0 - for the conversion of pyridoxal oxime.3 The yield of the hutyl-3-hydroxy-4,5-bis-(h droxymethy1)-pyridine and 2non no ethyl acetal of 2-ethyl-3-hydroxy-4-formyl-5-hydrox~n-amyl-3-hydroxy-4,5-bis-rhydroxymethyl)-pyridine were methylpyridine hydrochloride was 1.66 g. (39%); m.p similar to reactions previously described.'f6 Only the physi- 137.,5-138.5'. After one recrystallization from alcoholcal properties of the intermediates and products are listed ether containing a little hydrogen chloride and another rehere. from alcohol containing a little hydrogen 2-Is0butyl-4-methoxymethy1-5-cyano-6-hydroxypyridinecrystallization chloride, the material melted at 132-133'. IIIA) was prepared from l-methoxp-7-methyl-2,4-heptane.incd. Calcd. for C1~HieS03C1:C, 53.77; H , fi56; I;, dione (IA) (b.p 113' (24 mm.), n Z 91.4596). ~ After one recrrstalliz,ition froin ethi 1 alcohol, the product melted at 5.70 Found: C, ,54.00; H, 6.29; S , 5 63. 204-205" RESEARCH LABORATORIES .Ind Calcd. for CILHI~NZO~: C, 65.43; H , 7.32; S, MERCKA N D Co., Isc. R A H K A Y , S E T V JERSEY 12 72. Found: C, 65.68; H, 7.25; N, 12.71. 2-Isobutyl-3-nitro4methoxymethyl-5-cyano-6-hydroxypyridine (IIIA) was purified by two recrystallizations from ethyl alcohol, accompanied by decolorization with Darco; Chemistry of Vitamin B6. XI. Homologs of 4I l l 1, 167-168" Desoxypyridoxine Ancil. Calcd. for C12H16X304: C, 54.33; H , 5.70; S, 1.7.83. Found: C, 64.62; H , 5.50; i S,15.83. BY DOROTHEA HEYL,EILEENLuz, STANTON A. HARRISAxD KARLFOLKERS 2-Isobutyl-3-nitro-4-methoxymethyl-5-cyano-6-chloropyridine (IVA) IWS recrystallized three tiyes from petroleum RECEIVED APRIL22, 1953 ither ( h . p . 30 I t melted at 42-43 . 4-Desoxypyridoxine was shown to be a potent Anal. Calcti. for C I Z H ~ ~ N ~ C, O ~50.80; C ~ : H, 4.96; S, 14.82. Found: C , 30.82; H , 5.12; S , 1S.08. vitamin RE inhibitor.' Because of the biological 2-Isobutyl-3-hydroxy-4,5-bis-( hydroxymethy1)-pyridine interest in this compound, the preparation of hydrochloride (VA) was recrystallized from hot water, with homologs for further biological study was underdecolorization with Darco; 1n.p. 21.'-214°. taken. Three homologs, represented by structure Anal. Calcd. for CliHl&OaC1: C, 53.33; H, 7.32; S, 111, in which the methyl group in position 2 of 45.66. Found: C, 53.35; H , 7.2B; N, 5.91). desoxypyridoxine has been replaced by ethyl, isol-Methoxy-2,4-nonanedione (IB).-Condensation of methyl methoxyacetate with methyl n-amyl ketone yielded butyl and n-amyl groups, have now been prepared l-methoxy-2,4-nonancdione; h .p. 138 O (28 mm .), n% by svnthesis through the intermediates I and 11. I .4fia.
verted to the monoethyl acetal VII. These redctions are analogous to those previously described for the corresponding pyridoxal derivative^.^,^
7
2-n-Amyl-4-methoxymethyl-5-cyano-6-hydroxypyridine (IIB) waq recrvstallized twice from ab5olute alcohol; m.p 131-1:E0 I I1 Anal. Calcd. for C i ~ H I R S ~ C, O ~66.84; : H , 7.74; S, CH, 11 96. Found: C, 66.74; H, 7.64; N, 12.05. 2-~t-Amyl-3-nitro-4-methoxymethyl-5-cyano-6-hydroxypyridine (IIIB) n as recrystallized twice from alcohol and once from dilute alcohol. It melted a t 161-162'. Anal. Calcd. for C11HI,S30a: C, 55.90; H , 6 14; Y , I11 15.05. Found: C, 56.25; H, 5.79; 9,15-24. 2-n-Amyl-3-nitro-4-methoxymethyl-5-cyano-6-ch~oropyri2-Ethyl-3-hydroxy-4 methyl 5 hydroxymethylpydine (IVB) was recrystallized twice from petroleum ether ridine hydrochloride and 2-isobutyl-3-hydroxyi b p 30-60'1; m p 42-43'. 4 methyl 5 - hydroxymethylpyridine hydrochloAnal Calcd. for C I ~ H 1 ~ S 3 0 3 C C,l : 52.43; H, ,542; ride have also been prepared by the direct hyS ,14.11. Found: C, 52.16; H , 5.00; N, 14.20. 2-n-Amyl-3-hydroxy-4,S-bis-(hydroxymethy1)-pyridine hy- drogenolysis of the 2-ethyl-3-hydroxy-4,5-bis-(hydrochloride (VBj was recrystallized from alcohol containing droxymethy1)-pyridine hydrochloride2 and 2-isotrace of hydrogeri chloride. The product melted at 186- butyl - 3 - hydroxy - 4'5 - bis - (hydroxymethy1)-
-
-
187O.
A n a l . Calcd. for C ~ Z H Z O X O ~CC, ~!5.05; : S ,5.36. Found: C , 54.93; H , 7.82; N, 0.47,
H. 7 70;
'2) D Heyl, Ibld., 70,3434 (1948) (3) 6. A. Harris, 0 Heyl and K. Folkers, tbid , 86, 2088 (1044). (4) We w e indebted to Mr. Richard Boos and his associatea for the fnicroanal yses (6) 4 h Umls rnd Y. Falkers, THISJoaR*r!+,(2, IZ48, 3887
(lPlQ1,
- -
-
pyridine hydrochloride. Hydrogenolysis of pyridoxine hydrochloride to form 4-desoxypyridoxine hydrochloride was described previously. (1) W. H. Ott, Proc. SOC.Ex+. B i d . Med., 61, 125 (1946): W.W Qtovtes all6 B. €$. Sndl, Ibid., 'HI 73 (1948). (2) 6. A. # & i C und A. N. Wilson, THISl o u n ~ ~ LI S. ,, 2626 (1841). (a) r). H@Yl,B, LUL. 9. A. Harris and K. Folkerr, Cbid , 78, 4078 {igsa). (4) R. A, #M",4bId.i Ofif #POL) (1940).
