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Synthesis of substituted phenyl β-D -galactopyranosides
124
CARBOHYDRATE
RE%ARCH
Note
Synthesis
of substituted
phenyl
fl-D-galactopyranosides
C. K. DE BRUYNE ANDJ. WOUTERS-LEYSEN Laboratorium Algemene (Belgium)
en Biologrsche Scheikunde, H. I. K. W., Ledeganckstraat 35, B-9000
Gent
(Received September 2&t, 1970: accepted for pubhcation, October ZOth, 1970)
In Table I, a series of tetra-O-acetyl-P-D-galactopyranosides of substituted phenols are described. They were obtained by the reaction of tetra-O-acetyl-a-Dgalactopyranosyl bromide’ or penta-O-acetyl-fi-D-galactose’ with the appropriate phenol. Deacetylation with sodium methoxide3 yielded the corresponding B-Dgalactopyranosides (Table II). EXPERIMENTAL
Method 1, Koenigs-Knorr4*5 synthesis in the presence of yellow mercuric oxide and mercuric bromide. Method 2, modified Michae16*8 synthesis. Method 3, Helferich” ’ melt with toluene-p-sulphonic acid. In each case, the acetate was crystallized from methanol or methanol-water. The melting points were determined with a Mettler FP 2 instrument and are uncorrected. The optical rotations were measured on 0.5% solutions in chloroform or methanol with a Perk&Elmer Model 141 photoelectric polarimeter. The purity of the products was tested by t.1.c. on Silica Gel G (Merck) in acetic acid-water-ethyl acetate (1: 1:3) for the galactosides, and ethyl acetate-benzene (3:7) for the acetates. Detection was effected with 5% sulphuric acid in ethanol (10 min at 120’). ACKNOWLEDGMENT
We thank Prof. Dr. L. Massart for his interest in the work, and Miss J. De Lat for performing the microanalyses. REFERENCES 1 A. THO~~PS~N AND M. L. WoLFRor.1, Methods Carbohyd. Chem., 2 (1963) 221. Textbook of Practical Organic Chemistry, Longmans. Green and Co., London, 3rd edn., 1957, p. 452. 3 A. THOMPSON AND M. L. WOLFROM, Merho& Carbohyci. Chem.. 2 (1963) 215. 4 W. KOENIGS AND E. KNORR, Ber., 34 (1901) 957. 5 L. R. SCHROEDERAND J. W. GREEN, J. Chem. Sot., C, (1966) 530 6 F. G. LOONTIENS AND C. K. DE BRUYNE, Natarwissenschuften, 51 (1964) 359. 7 B. HE-RICH AND E. SCHMITZ-HILLEEUXCHT, Ber., 66 (1933) 378. 8 C. K. DE BRUME AND F. VAN WI JNENDAELE, Curbohyd. Res.. 4 (1967) 102. 2 A. I. VOGEL, A
Carbohyd. Res.
18 (1971) 124-126
TABLE 1
Method
3 2 3 2 2 2 1 2 1 2 2 2 2 2 3 3 3 2 2 2 2 2 2 2 3 3 2 2
Substituent
ndhloro o-Chloro p-Bromo m-Bromo o-Bromo o-Methyl p_Methoxy m-Methoxy o-Methoxy p_Ethoxy m-Ethoxy p_Acetyl m-Acetyl o-Acetyl p-Ethyl p-rert-Butyl 3,CDimethyl 2,CDlchloro 3,4-Dlchloro 2,dDlchloro 2,5-Dshloro 2,4-Dibromo 2-Nitro-Cmethyl 2.Nltro-4-chloro 2,3,5-Tnmethyl 2,4,6-Tnmelhyl 2,4,6-Tnchloro 2,4,6-Tnbromo 42 20 46 30 30 45 40 13 54 60 50 41 50 10 44 40 67 40 40 61 52 50 31 33 25 48 60
Yield (%)
A~GT~LAT~OPHENYLP-D-OALACT~P~RANOSIDES
70-71 137-138 102-103 90-91 141-142 109-110 102-103 87-88 102-103 82-83 Ill-112 146-147 118-119 150-151 98-99 100-102 134-135 130-131 81-82 syrup 154-155 118-119 192-193 199-200 137-138 H-145 123-124 136-137
h4.p. (degrees)
-8.7 -23.1 $51.7 -t 55.9 -0.9 -11.6 - 13.0 - 12.4
-28.3 -l-O.6 t1.2 - 32.6 -4,7 -l-2.9 -to.3 - 16.6 +3.6 tl.8 -0.8 -8.3 -27.6 i-4.7 t7.0 t2.1 -25.4 -to.7
0
~~&I (degrees)
-8.3 - 60.5 $5.6 -1.4 - 70.2 - 13.9 +4.4 -3.9 -38.7 -1-5.5 0 -7.8 - 27.3 - 74.9 -47.4 + 12.2 $4.7 - 53.5 -2.7 -20.9 -51.0 i-245.0 +252.0 -8.1 -24.6 -27.2 -26.0
(degrees)
bl%,
5.0 5.1 4.5 4.6 4.6 5,9 5.6 5.7 5.8 6.0 6.0 5.8 5-8 5,7 6.0 6.6 6.2 4.7 4.7 4.6 3,9 5,3 4.7 6.4 6.4 4.0 3.3
47.5 47.7 47.6 57.4 55.4 55.4 55.3 56.4 56.4 56.5 56.4 56.3 58.3 59.9 58.3 48.4 48.3 48.7 41.2 52.1 47.5 59.0 59.2 45.4 36.1
H
52.3 52.0
C
Found (X)
6.0 5.8
56.4 56.5
CzJ-&d,, GzH17O11
64 4.0 3.2
59.2 45.5 36.3
C23H30010
4.5 41.2 3.8 52.2 5.2 47.7 4.4
48.7 CzoH~zBrzOlo CZIH~SNOIZ Go&&lNOlz
C2oHzaCl2O,o
CZZHVJOIO
C24H320‘0
58.4 602 60.0 6.7 58.4 6.2
5.7
55.5
Cz~Hzd&l
CazHd~o
5.9
4.6
5.0
H
57.5
47.7
52.3
C
Crrlc. (%)
CZI&&O
Cdk3Br010
’ Cz0&1C~3010 CzeH~lBr~O1O
I j
1
1
z
CZOH~JOIO
Forrrwlo
;;I
3
168-169 203-205 176-177 169-170 217-218 179-l 80 157-158 141-142 207-209 182-183 150-151 220-221 170-171 177-178 144-145 155-156 181-182 210 (dccomp.) 169-l 70 172-174 207-208 220-222 197-198 201-202 207-208 228-230 21l-21 5 224-225
mChloro o-Chloro p-Bromo nfiBrom0 odromo o-Methyl p-Methoxy m-Methoxy o-Mcthoxy p_Ethoxy m-Ethoxy p_Acetyl npAccty1 o-Acetyl pEthy1 p-t&WButyl J&Dimethyl 2,4-Dichloro 3,4-Dichloro 2,6-Dichloro 2,SDichloro 2,4-Dibromo 2-Nltro-4.methyl 2-Nitro-4.chloro 2,3,5-Tnmethyl 2,4,6-Trimethyl 2,4,6-Trlchloro 2,4,6-Tnbromo A B A A A A A A A A A B A A B B A A B B B A A A C A A A
SOIuCNr~
-35.7 -45.4 -44.6 -45.8 - 39.7 -4200 -43.1 -4808 -47,3 -42.5 -49.5 - 66,9 - 62.4 - 39.0 - 54.1 - 39.0 - 42.6 -46.8 - 52.1 0 - 54.9 -37.6 -46.3 -64.8 -38.5 -0.8 -1.9 +3.0
[cxJ& (degrees)
-93.4 - 104.2 - 103.9 -92.7 - 105.9 -158.4 - 142.7 -74.1 - 92.4 -82.6 -91.8 - 100, - 108.2 -3.0 -118.0 -79.1 -115.1 - 184.4 -84.6 -5.8 -6.4 t6.0
-85.1
-76.9 -94.5 -96.4 -98.4
W:LXY (degrees)
49.7 49.6 42.7 42.9 42.9 57.6 54.2 54.4 54.6 55.9 55.9 56.2 56.1 56.3 59.0 61.0 59.1 44 5 44.4 44.3 44.6 34.7 49.5 42.6 60.3 6003 40.0 29,2
c 5,4 5,2 4.5 4,6 485 6.6 6,3 6.3 6,3 6.7 6.7 6.1 6.3 6.4 6.9 7.7 7.1 4.3 4.3 4.3 4.5 3.5 5,5 4.5 7.4 7.5 3.5 2.7
H
Found (%)
“Crystallnntions were cffccted from the following solvents A, methanol; B, water; C, water-methanol.
Map. (degees)
P.D.~ALACT~~YRAN~SIDES
Substitllent
PHE~L
TABLE II
’
]
I
1
C1&3Br&
Cl2HISCh06
ClzH14BrzOs GJHI~NGI GzHdZlOe -- C, &2206
ClZHl4CI206
Cl4132006
3.4 5.4 4.2 7.4 3.6 2.6
34.8 49.5 42.9 60.4 40.1 29.2
4.3
7.0 7.7 7.0
59.2 61.5 59.2 C&2406
44.3
6.4
56.2 %$I1907 C14H2006
6.7
6.3 56.0
54.6
6.6
C14H2007
C13&307
57.8
4,5
43.0
C&lsBrOa G&II eGi
5.2
H
49.6
c
Calc. (%)
C12H1&106
Formula
;;I
Y
i3 o\
CARBOHYDRATE
RE%ARCH
Note
Synthesis
of substituted
phenyl
fl-D-galactopyranosides
C. K. DE BRUYNE ANDJ. WOUTERS-LEYSEN Laboratorium Algemene (Belgium)
en Biologrsche Scheikunde, H. I. K. W., Ledeganckstraat 35, B-9000
Gent
(Received September 2&t, 1970: accepted for pubhcation, October ZOth, 1970)
In Table I, a series of tetra-O-acetyl-P-D-galactopyranosides of substituted phenols are described. They were obtained by the reaction of tetra-O-acetyl-a-Dgalactopyranosyl bromide’ or penta-O-acetyl-fi-D-galactose’ with the appropriate phenol. Deacetylation with sodium methoxide3 yielded the corresponding B-Dgalactopyranosides (Table II). EXPERIMENTAL
Method 1, Koenigs-Knorr4*5 synthesis in the presence of yellow mercuric oxide and mercuric bromide. Method 2, modified Michae16*8 synthesis. Method 3, Helferich” ’ melt with toluene-p-sulphonic acid. In each case, the acetate was crystallized from methanol or methanol-water. The melting points were determined with a Mettler FP 2 instrument and are uncorrected. The optical rotations were measured on 0.5% solutions in chloroform or methanol with a Perk&Elmer Model 141 photoelectric polarimeter. The purity of the products was tested by t.1.c. on Silica Gel G (Merck) in acetic acid-water-ethyl acetate (1: 1:3) for the galactosides, and ethyl acetate-benzene (3:7) for the acetates. Detection was effected with 5% sulphuric acid in ethanol (10 min at 120’). ACKNOWLEDGMENT
We thank Prof. Dr. L. Massart for his interest in the work, and Miss J. De Lat for performing the microanalyses. REFERENCES 1 A. THO~~PS~N AND M. L. WoLFRor.1, Methods Carbohyd. Chem., 2 (1963) 221. Textbook of Practical Organic Chemistry, Longmans. Green and Co., London, 3rd edn., 1957, p. 452. 3 A. THOMPSON AND M. L. WOLFROM, Merho& Carbohyci. Chem.. 2 (1963) 215. 4 W. KOENIGS AND E. KNORR, Ber., 34 (1901) 957. 5 L. R. SCHROEDERAND J. W. GREEN, J. Chem. Sot., C, (1966) 530 6 F. G. LOONTIENS AND C. K. DE BRUYNE, Natarwissenschuften, 51 (1964) 359. 7 B. HE-RICH AND E. SCHMITZ-HILLEEUXCHT, Ber., 66 (1933) 378. 8 C. K. DE BRUME AND F. VAN WI JNENDAELE, Curbohyd. Res.. 4 (1967) 102. 2 A. I. VOGEL, A
Carbohyd. Res.
18 (1971) 124-126
TABLE 1
Method
3 2 3 2 2 2 1 2 1 2 2 2 2 2 3 3 3 2 2 2 2 2 2 2 3 3 2 2
Substituent
ndhloro o-Chloro p-Bromo m-Bromo o-Bromo o-Methyl p_Methoxy m-Methoxy o-Methoxy p_Ethoxy m-Ethoxy p_Acetyl m-Acetyl o-Acetyl p-Ethyl p-rert-Butyl 3,CDimethyl 2,CDlchloro 3,4-Dlchloro 2,dDlchloro 2,5-Dshloro 2,4-Dibromo 2-Nitro-Cmethyl 2.Nltro-4-chloro 2,3,5-Tnmethyl 2,4,6-Tnmelhyl 2,4,6-Tnchloro 2,4,6-Tnbromo 42 20 46 30 30 45 40 13 54 60 50 41 50 10 44 40 67 40 40 61 52 50 31 33 25 48 60
Yield (%)
A~GT~LAT~OPHENYLP-D-OALACT~P~RANOSIDES
70-71 137-138 102-103 90-91 141-142 109-110 102-103 87-88 102-103 82-83 Ill-112 146-147 118-119 150-151 98-99 100-102 134-135 130-131 81-82 syrup 154-155 118-119 192-193 199-200 137-138 H-145 123-124 136-137
h4.p. (degrees)
-8.7 -23.1 $51.7 -t 55.9 -0.9 -11.6 - 13.0 - 12.4
-28.3 -l-O.6 t1.2 - 32.6 -4,7 -l-2.9 -to.3 - 16.6 +3.6 tl.8 -0.8 -8.3 -27.6 i-4.7 t7.0 t2.1 -25.4 -to.7
0
~~&I (degrees)
-8.3 - 60.5 $5.6 -1.4 - 70.2 - 13.9 +4.4 -3.9 -38.7 -1-5.5 0 -7.8 - 27.3 - 74.9 -47.4 + 12.2 $4.7 - 53.5 -2.7 -20.9 -51.0 i-245.0 +252.0 -8.1 -24.6 -27.2 -26.0
(degrees)
bl%,
5.0 5.1 4.5 4.6 4.6 5,9 5.6 5.7 5.8 6.0 6.0 5.8 5-8 5,7 6.0 6.6 6.2 4.7 4.7 4.6 3,9 5,3 4.7 6.4 6.4 4.0 3.3
47.5 47.7 47.6 57.4 55.4 55.4 55.3 56.4 56.4 56.5 56.4 56.3 58.3 59.9 58.3 48.4 48.3 48.7 41.2 52.1 47.5 59.0 59.2 45.4 36.1
H
52.3 52.0
C
Found (X)
6.0 5.8
56.4 56.5
CzJ-&d,, GzH17O11
64 4.0 3.2
59.2 45.5 36.3
C23H30010
4.5 41.2 3.8 52.2 5.2 47.7 4.4
48.7 CzoH~zBrzOlo CZIH~SNOIZ Go&&lNOlz
C2oHzaCl2O,o
CZZHVJOIO
C24H320‘0
58.4 602 60.0 6.7 58.4 6.2
5.7
55.5
Cz~Hzd&l
CazHd~o
5.9
4.6
5.0
H
57.5
47.7
52.3
C
Crrlc. (%)
CZI&&O
Cdk3Br010
’ Cz0&1C~3010 CzeH~lBr~O1O
I j
1
1
z
CZOH~JOIO
Forrrwlo
;;I
3
168-169 203-205 176-177 169-170 217-218 179-l 80 157-158 141-142 207-209 182-183 150-151 220-221 170-171 177-178 144-145 155-156 181-182 210 (dccomp.) 169-l 70 172-174 207-208 220-222 197-198 201-202 207-208 228-230 21l-21 5 224-225
mChloro o-Chloro p-Bromo nfiBrom0 odromo o-Methyl p-Methoxy m-Methoxy o-Mcthoxy p_Ethoxy m-Ethoxy p_Acetyl npAccty1 o-Acetyl pEthy1 p-t&WButyl J&Dimethyl 2,4-Dichloro 3,4-Dichloro 2,6-Dichloro 2,SDichloro 2,4-Dibromo 2-Nltro-4.methyl 2-Nitro-4.chloro 2,3,5-Tnmethyl 2,4,6-Trimethyl 2,4,6-Trlchloro 2,4,6-Tnbromo A B A A A A A A A A A B A A B B A A B B B A A A C A A A
SOIuCNr~
-35.7 -45.4 -44.6 -45.8 - 39.7 -4200 -43.1 -4808 -47,3 -42.5 -49.5 - 66,9 - 62.4 - 39.0 - 54.1 - 39.0 - 42.6 -46.8 - 52.1 0 - 54.9 -37.6 -46.3 -64.8 -38.5 -0.8 -1.9 +3.0
[cxJ& (degrees)
-93.4 - 104.2 - 103.9 -92.7 - 105.9 -158.4 - 142.7 -74.1 - 92.4 -82.6 -91.8 - 100, - 108.2 -3.0 -118.0 -79.1 -115.1 - 184.4 -84.6 -5.8 -6.4 t6.0
-85.1
-76.9 -94.5 -96.4 -98.4
W:LXY (degrees)
49.7 49.6 42.7 42.9 42.9 57.6 54.2 54.4 54.6 55.9 55.9 56.2 56.1 56.3 59.0 61.0 59.1 44 5 44.4 44.3 44.6 34.7 49.5 42.6 60.3 6003 40.0 29,2
c 5,4 5,2 4.5 4,6 485 6.6 6,3 6.3 6,3 6.7 6.7 6.1 6.3 6.4 6.9 7.7 7.1 4.3 4.3 4.3 4.5 3.5 5,5 4.5 7.4 7.5 3.5 2.7
H
Found (%)
“Crystallnntions were cffccted from the following solvents A, methanol; B, water; C, water-methanol.
Map. (degees)
P.D.~ALACT~~YRAN~SIDES
Substitllent
PHE~L
TABLE II
’
]
I
1
C1&3Br&
Cl2HISCh06
ClzH14BrzOs GJHI~NGI GzHdZlOe -- C, &2206
ClZHl4CI206
Cl4132006
3.4 5.4 4.2 7.4 3.6 2.6
34.8 49.5 42.9 60.4 40.1 29.2
4.3
7.0 7.7 7.0
59.2 61.5 59.2 C&2406
44.3
6.4
56.2 %$I1907 C14H2006
6.7
6.3 56.0
54.6
6.6
C14H2007
C13&307
57.8
4,5
43.0
C&lsBrOa G&II eGi
5.2
H
49.6
c
Calc. (%)
C12H1&106
Formula
;;I
Y
i3 o\