889 TABLEI D-thTeO-l-(p-ACYLPHENYL)-1,3-PROP.INEDIOLS AKD DERIVATIVES
OH H Compd 1 I1 111
R1
%------Found, %N C I C H N C I 4.38 22.15 48.48 4.86 4.25 22.35 4.02 20.36 51.73 5.50 4.26 20.38 3.66 18.55 56.84 4.55 3.81 18.74
H H I1
blp, 'C 125-127 97-99 160-161
Formula +13.4 (1.25) CnHd2hNO4 +14 ( 0 . 8 ) CisHisClnSOa + 7 . 8 (0.9) CisHiiCI?SO4
--Calcd, C H 48.76 4.72 51.73 5.50 56.55 4.48
CHCIzCO
I1
163-164
+ 10.5(1.05)
55.68 5.97 3.61 18.26 55,il 5.86 3.66 18.40
CHC12CO ClIaCO 1i
€I I1 I1
130 166-167 139-140
+7 (0.5) -24.5 (1,551
R2
Ra
CHaCO (CHdlCIICO CeHsCO
CHCllCO CHC12CO CIICI,CO
IV
Oco
Inh 11, IC
CHCO CHIC0 CHaCO
[aI25~ deg ,
(cja
CisH?1ChS04
48.76 4.72 4.38 22.15 48.70 4.82 4.48 22.04 61.85 6.95 5.55 62.13 6.82 5.57 63.14 7.23 6 . 6 9 63.03 7.45 6.46
NNH C SN H?
Id Ie If Ig
I1
CHIC CHICO CHICO ~-CBHICOCH~
CHClzCO H 17V C H C I C O C O ( C H ? ) C O I H 123-124 81-82 C H C l C O CHa(CH,)iaCO 187-189 CHClCO H
f9.5 (0.45)
Ci4HisChN403S CiIHiYCl??iOi CnsHdsC12NOs C?2HziCI?NOs
42.75 4.62 14.25 18.03 42.74 4.83 14.46 17.89 48.59 4.56 3.33 16.87 48.55 4.60 3.35 16.91 62.36 8.12 2.50 12.69 62.10 8.17 2.64 12.77 18.62 58.68 4.io 16.75 58.89 4.93
I
Ih IIa IIb IIIa IIIb IIIc
CH=CHCO CeHsCH=CHCO (CHI)?CHCO (CHa)?CHCO CeHsC(=XH) C6HsCO CeHsCHOH
IVa
~
IVb
0-
C
CHClOCO CHaCO H CHaCO CHKO CHCI-CO O CHICO
CHCIXO
CmHisClrNOa CiaHziN01 -22 (1.05) Cl3H19~03 f3.2 (0.95) C I ~ H ~ N ~ O + 5 . 6 (0.95) CisHisNOn +5.F) (1.1) CisHieCI?NOa +5.5(0.65) + 2 (1.15)
H H H
155-156 138-139 108-109 186-187 139-140 129-130
H
184-185
+3 (1)
H
112-113
H
H H
a Concentration in methanol. DL form. softening but no definite melting up to 320".
58.84 4.69 64.49 7.58 65.80 8.07 I 69.21 6.43 68.99 6.11 56.26 4.98
li.37 58.71 4.80 64.20 7.58 66.01 7.96 8.97 68 93 6.31 4.47 69.16 5.98 18.46 56.17 5.12 5.01 5.90
CiaHzsNOa
D7.68 7.89 4.38
C?oH?iChNOs
55.56 6.29
17.22 5.01 5.66 8.74 4.53 18.25
67.88 8.01 4.60
16.40 55.59 6.52
16.43
At 176" there is a sharp change in color to orange followed by gradual darkening and
mum inhibitory concentrations are as follows (in ug/ml): 11, S.. aweug (WLRI-25), 31; E . coli, 62; P . vulgayis, 125; 111,IV, Ib, and IIa, X.auwus (WTARIX ) , >12-5; E. coli, >125.
Experimental Section Physical constants and arialyt,ical values are reported in Table
I. Melting points were determined using the Thomas-Hoover capillary melting point apparatus which was calibrated against known standards. The ultraviolet and infrared spectra were obtained, respectively, with a Beckman DK-1 spect'rophot,ometer and a Baird Model 455 double-beam instrument. Unlers otherwise stated, the former were determined as solutions in 95% ethanol and the lat'ter as Sujol mulls. Tetrahydrofuran ( T H F ) used was purified and dried by distillation from LiAlH,. Prior t o evaporation or concentration, the nonaqueons organic solut,ions were dried over Na2S04. The evaporations and concentrations were carried out in vacuo with a rot8aryflash evaporator at, temperatures not exceeding 30". ~-threo-2-Acetamido-l-(~-cyanophenyl)-l,3-propanediol was prepared as describedl for the corresponding DL compound: ~ (e 3, CILOH); vmaL (cm-I) 2300 mp 122.5; [ a I z 5 +4.1" ( C s X ) , 1645 (amide C=O). Anal. Calcd for Cl2Hl4X2O3:C, 61.53; H, 6.02; IL', 11.96. Found: C, 61.65; H, 6.17; N, 11.82. D-threo-l-( p-Acetylphenyl)-2-( 2,2-dichloroacetamido)-1,3-propanediol (I).-Ethereal CHILi (300 ml, 0.8 LV)was added at 40" over a period of 4 hr to a stirred solution of 8 g of D-threo-1-(pcyanophenyl)-2-acetamido-1,3-propanediolin 600 ml of THF. After 2 hr of additional stirring, a solution of 100 g of (NH4)2SO4 in 100 ml of water was added over a period of 1 hr. The organic layer was separated; the aqueous phase was extracted four times with 200-ml portions of ethyl acetate-THF (1: 1). The extracts were combined with the organic layer, dried (Na2SOa),and evaporated. The residiie was heated on a steam bath with 300 ml of 10% I T 8 0 4 for 3 hr. The sollition was cooled, washed twice with 25-ml portions of ethyl acletat>e,made basic with 20% KOIl at 0-3', and estixcated eight times with 400-ml portions of ethyl
acetate. The combined extracts were dried and evaporated. The residue was refluxed for 4 hr with 13 ml of methyl dichloroacetate in 50 ml of methanol. hfter evaporation, the oily residue was passed through 100 g of an activated magnesium silicate column (Florisil) which was eluted with ethyl acetate. The crystalline fractions were combined and recrystallized from ethyl acetate-hexane ( 1 : l ) to give 2.8 g of product: Xmnx [mfi ( e ) ] 252.5 (15,7c50). vmax (em-') 1672 (amide C=O), 1693 (ketone C=O); v:::c"(cm-l) 1685 (ketone C=O), 1708 (amide C=O).6 In an alternate procedure, the solution of 1.5 g of o-threo-l(p-cyanophenyl)-2-acetamido-1,3-propanediolin T H F (400 ml) was treated with 1.50 ml of 1 S ethereal C H J I g I over a period of 23 hr a t reflux temperature. The reaction mixture was worked up as above to give 0.46 g of product. DL-threo-l-( p-Acetylphenyl)-2-( 2,2-dichloroacetamido)-1,3propanediol (Ia) was prepared from o~-threo-l-(p-cyanophenyl)-2acetamido-1,3-propanediolby the above procedure. ~-threo-l-(p-Acetylphenyl)-2-acetamido-l,3-propanediol (Ib) was prepared by the above procedure omit,ting the hydrolysis and dichloroacetylation steps; vmar (cm-1) 1634 (amide C=O) and 1676 (ketone C=O). ~-threo-l-(p-Acetylphenyl)-2-am~no-1,3-propaned~ol (IC).-A suspension of 2.5 g of I in 25 ml of 107, H?SOI was heated on a steam bath for 3 hr. After cooling, the solution was washed with 50 ml of ethyl acetate, made basic with NH40H a t 0-5', aiid extracted five times with 150-ml portions of ethyl acetate. The combined extracts were dried and concentrated to ca. 25 ml to give on cooling 1.05 g of off-white crystals which were recrystallized from ethyl acetate: vmgX (cm-l) 1678 (ketone C=O), v~~~~~ (cm-1) 1682 (ketone C=O). D-threo-1 -( p-Acetylpheny1)-2-( 2,2-dichloroacetamido)-1,3-propanediol Thiosemicarbazone (Id).-A solution of 0.132 g of I and 0.037 g of thiosemicarbazide in 25 ml methanol was refluxed for
(6) T h e dicliloracetamido carhonyl band undergoes a 25-35-em-' shift t o liigher frequency on passage from mull t o solution (see example 1110). The hand of the ketone function shifts only slightly or remains a t the same position (see examples IC a n d IIh). A s a result, t h e absorption frequency of tlie dicliloroacetyl carhonyl is believed to be below t h a t of tlie ketone carbunhl wllen determined as a mull and above it when determined in soliition.
