X-Ray Diffraction Powder Data for Some 1,3,4-0xadiazoles R A L P H R. PFEIFFER Lilly Research LaCoratories,
Indianapolis 6, Ind.
X-ray diffraction powder data were obtained as part of an effort to characterize a number of substituted 1,3,4oxadiazoles physically. The diffraction data for fourteen of these are presented for the benefit of others interested in the compounds and in a convenient and specific means of their identification.
A
Most of the reported products are crystalline solids and can be conveniently identified by x-ray powder diffraction; therefore, these data have been assembled (Table I) for the benefit of others interested in the synthesis of the compounds. For convenience in indexing, the three strongest lines and innermost line of each pattern are listed (Table 11).
RECENT publication ( I ) from this laboratory described the preparation of a number of 2-aryl- and 2-alkyl-5-aryl-
1,3,4oxadiazoles :
Table I. d , A. I/Ii 2-Phenyl1 ,3.4-oxadiazolea, CsHsNzO 8.65 0.40 5.77 0.15 5.26 1.00 4.65 0.65 4.30 0.65 3.96 0.15 3.75 0.40 3.15 0.25 3.09 0.25 2.48 0.15 2.03 0.15 2-(3-Pyridyl)1,3.4-oxadiazole, CiHsNaO 10.4 0.02 0.30 9.67 6.93 0.05 5.00 0.40 4.84 0.40 4.63 0.05 4.44 0.10 0.15 4.34 0.02 4.20 0.30 3.71 3.58 0.10 3.47 0.05 3.36 0.05 3.29 1.00 3.20 0.10 3.09 0.05 3.03 0.02 2.96 0.05 2.82 0.05 2.75 0.05 2.70 0.05 2.52 0.05 2.48 0.05 2.41 0.05 2.36 0.05 2.32 0.05 0.05 2.27 0.05 2.09 0.05 1.897 2-Ethyl-5(4-pyridylj-1,3,4oxadiazole, CgHPNaO 13.3 0 02 11.8 0.60 8.01 0,lO 6.05 0.10 5.85 0.10 5.38 0.05 5.0.5 0.10 4.77 0.15 4.33 1.00 4.13 0.20 3.96 0.02 3.83 0.02 3.70 0.05 3.55 0.10 3.38 0.30 3.20 0.40 3.07 0.02 3.00 0.10 2.92 0.15 a Hynroscopic
Principal Powder Diffracition Lines and Relatiive Intensities d , A. I 'I: d , A. I/Il d. A. III;
d . A. IiIi 2-Et hyl-5(4-pyridyl)-1,3.4oxadiazole, CgHpNaO (contd.) 2.81 0.10 2.71 0.05 2.65 0.05 2.52 0.02 2.36 0.02 2.32 0.02 2.24 0.02 2.19 0.02 2.16 0.02 2.10 0.02 2.05 0.05 2.01 0.02 1.983 0.02 1.840 0.02 1.794 0.05 2- (p-Chlorophenyl). 1,3,4-oxadiazole, CsHrClNiO 8.28 0.05 5.87 0.15 5,62 0.05 4.89 0.65 4.49 0.40 3.76 0.25 3.64 0.40 3.51 0.25 3.46 0.15 3.24 1.00 3.20 0.15 3.13 0.15 2.97 0.15 2- (2-Quino1yl)1,3,4-oxadiazole, CiiHiNiO 9.92 0.15 7.74 0.40 6.02 0.10 5.85 0.05 5.00 0.10 5.34 1.00 5,15 0.05 4.90 0.05 4.82 0.10 4.40 0.05 3.99 0.10 3.85 0.15 3.78 0.05 3.62 0.30 3.59 0.40 3.51 0.05 3.44 0.40 3.24 1.00 3.12 0.05 3.01 0.10 2.77 0.05 2.72 0.05 2.67 0.05 2.59 0.05 2.54 0.05 2.39 0.05 2.26 0.05 2.18 0.05 2.15 0.06 2.07 0.05
2-Methyl 5-(4-pyridyl) 1,3,4-oxadiacole, CsHiNiO (contd.) 4.10 0.05 3.98 0.02 3.62 1.00 3.45 0.02 3.37 0.02 3.29 1.00 3.26 0.65 3.14 0.02 2.96 0.02 2.78 0.02 2.60 0.02 0.02 2.52 0.05 2.44 0.05 2.33 2.28 0.02 2.21 0.02 0.02 2.17 0.02 2.04 0.02 1.983 1,901 0.02 1.835 0.10 1.651 0.05
Z-(Z-Quinolyl)1,3,4-oxadiazole. CiiHiNaO (contd.) 2.05 0 05 1.994 0.05 1.894 0.05 1.786 0.05 1.755 0.05 1.673 0.05 1.619 0.05
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2- (2-Indoly1)1,3,4-oxadiasole, CioHiNiO 8.98 0.65 6.15 0.35 5.20 0.65 4.98 0 35 4.79 0.35 4.49 0.35 3.69 0.20 3.48 1.00 3.36 0.35 3.08 0.35 2.74 0.35 Z-(o-Methoxyphenyl)1,3 4-oxadiacole, C 9 ~ , ~ I ~ I 10.0 0.10 9.26 0.10 8.41 0.30 7.26 0.20 6.65 1.00 5.87 0.05 5.30 0.10 4.42 0.10 4.18 0.15 3.92 0.05 3.81 0.05 3.70 0.15 3.61 0.15 3.46 0.05 3.36 1.00 3.15 0.20 3.08 0.15 2.92 0.05 2.76 O.G5 2.55 0 05 2.23 0.05 2.10 0.05 1.986 0.05 1.944 0.05 1.925 0.05 1.718 0.05
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2-Methyl 5- (4-pyridy1)1,3,4-oxadiaaole, CsHiNaO 9.92 0.40 6.90 0.02 5.80 0.02 5.58 0.01 5.26 1.00 5.08 0.65 4.89 0.20 4.64 0.15 4.21 0.02
206
2-(p-Nitropheny1)1,3.4-oxadiacole, CaH,NzOs 0.05 8.65 0.05 6.32 5.67 0.05 5.54 0.20 0.30 5.31 4.80 0.10 0.10 4.37 0.15 4.26 0.15 4.17 0.10 4.05 3.80 0.10 3.71 0.10 0.10 3.60 3.39 0.05 3.30 0.05 3.24 1.00 0.15 3.17 0.05 3.08 3.01 0.05 0.05 2.82 2.77 0.05 2-Methyl-5-phenyl1,3,4-oxadiazole, C*HSNIO 10.3 0.65 7.17 0.05 0.35 6.43 0.35 6.09 5.31 0.15 5.15 0.15 4.80 0.35 1.00 4.46 0.65 4.05 0.35 3.36 3.51 0.35 3.25 0.20 3.17 0.35 3.10 0.15 2.88 0.20
Z-Methyi-5-phenyl1,3,4-0xadiazole, C PHs Nz 0 (contd.) 2.52 0 0.5 2.48 0.05 2.45 0 05 2.40 0.05 2.35 0.05 2.12 0.05 2.07 0.05 1.914 0.05 1.862 0.0.5 1.817 0.05 1.688 0 03 2- (4-Pyridyl) 1,3,4-oxadiszole, C?HaNaO 9.19 0.15 7.95 0.05 7.14 0.02 6.51 0.60 5.30 0.40 5.07 0.05 4.79 0.60 4.58 I 00 3.98 0.15 3.81 0.10 3.70 0 15 3.44 0.19 3.34 0.05 3.25 0.40 3.18 0.05 3.09 0.05 3.01 0.05 2.84 0.02 2.77 0.02 2.6R 0.05 2.58 0.05 2.54 0.02 2.43 0.02 2.42 0.05 2.30 0.05 2.22 0.02 2.19 0.05 2.11 0.02 2.00 0.02 1.920 0.02 1.771 0.02 1.736 0 02 2-Ethy1-5(p-chlorophenyli. 1,3,4-oxadiaaole, C~QH~CIK~O 12.9 0.50 8.33 0.13 6.40 0.15 5.69 0.30 5.16 0.15 4.87 0.15 4.39 1.00 4.26 0 65 4.04 0.15 3.74 O,l5 3.54 0.40 3.37 0.50 3.30 0.40 3.15 0.15 2.99 0 50
d , A. I/Ii 2-Ethyl-5(p-chlorophenyl)1,3,4-oxadiazole. CIQHSCIN~O (contd.) 2.84 0.1; 2.48 0.15 2- (1-Xaphthyl)1,3,4-oxadiazole, CiiHsNzO 19.6 0.85 12.1 0.10 10.9 0.10 9,63 0.30 8.25 0.55 7.06 0.35 6.59 0 10 6.00 1.00 5.50 1.00 4.80 O.fi5 4.31 0.20 4.13 0.15 3.90 0.5; 3.76 1.00 3.66 0.55 3.60 0.5.S 3.49 0.20 3.43 0.26 3.35 0.65 3.28 0.15 3.21 1.oo 3.17 0.35 3.07 0.15 2.98 0.15 2.85 0.10 2.75 0.10 1.69 0.10 2.64 0.10 2.58 0.10 2.40 0.0,5 2.33 0.05 2.30 0.05 2.17 0.10 2.07 0.10 1.967 0.10 1.905 0.10 1.837 0.15 2-Ethyl-3(p-nitrophenyl) 1,3,4-oxadiazole, CIQH~NSOI 10.5 0.65 8.40 0.10 6.99 O.FJ 5.58 0.20 5.20 1.00 4.80 0.55 4.59 0.35 4.22 0.33 3.85 0.55 3.45 0.55 3.29 1.00 3.11 0.55 2.93 0.15 2.90 0.15 2.33 0.05 2.29 0.05 2.11 0.05 1.80 0.05
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V O L U M E 28, NO. 2, F E B R U A R Y 1 9 5 6 Table 11. 1,3.4-Oxadiazole Substituent(s1 2-Phenyl 2- (o-hlethoxyphenyl) 2- (p-Chlorophenyl) 2- (p-Nitrophenyl) 2-(l-Naphthyl) 2- (4-Pyridyl) 2- (3-Pyridyl) 2- (2-Quinolyl) 2-Methyl 5-phenyl, 2-Alethyl 5- (4-pyridyl) 2-Ethyl 5- (p-chlorophenyl) 2-Ethyl 5- (p-nitrophenyl) 2-Ethyl 5- (4-pyridyl) 2- (2-Indolyl)
207
Index Lines from Diffraction Patterns 1st 5 . 2 6 (1.00) 6 . 6 5 (1.00) 3.24 (1.00) 3.24 (1.00) 6.00 (1.00) 4 . 5 8 (1.00) 3 . 2 9 (1.00) 5 . 3 4 (1.00) 4.46 (1.00) 5 . 2 6 (1.00) 4.39 (1.00) 5.20 (1.00) 4 . 3 3 (1.00) 3 . 4 8 (1.00)
'
Strongest Lines 2nd 4 . 6 5 (0.65) 3 . 3 6 (1.00) 4 . 8 9 (0.65) 5 . 3 1 (0.30) 5 . 5 0 (1.00) 6.51 (0.60) 5.00 (0.40) 3.24 (1.00) 1 0 . 3 (0.65) 3 . 6 2 (1.00) 4.26 (0.65) 3 . 2 9 (1.00) 11.8 ( 0 . 6 0 ) 8 . 8 9 (0.65)
The samples were finely ground and packed into thin-walled Parlodion capillaries of about 0.5-mm. diameter. These were rotated during exposure in a camera with a 114.6-mm. diameter, using vanadium-filtered chromium radiation (CrK, = 2.2909 A. used in calculations). Relative intensities were determined by visual comparison with a standard series of photographic den-
Innermost Line 8 . 6 5 (0.40) 10.0 (0.10) 8 . 2 8 (0.05) 8 . 6 5 (0.05) 1 9 . 6 (0.85) 9 . 1 9 (0.15) 1 0 . 4 (0.02) 9 . 9 2 (0.15) 1 0 . 3 (0.65) 9 . 9 2 (0.40) 1 2 . 9 (0.50) 1 0 . 5 (0.65) 1 3 . 3 (0.02) 8.98 (0.65)
3rd 4 . 3 0 (0.65) 8 . 4 1 (0.30) 4 . 4 9 (0.40) 5 . 5 4 (0.20) 3.76 (1.00) 4 . 7 9 (0.60) 4 . 8 4 (0.40) 3 . 4 4 (0.40) 4.05 (0.65) 3.29 (1.00) 1 2 . 9 (0.50) 1 0 . 5 (0.65) 3.29 (0.40) 5 . 2 0 (0.65)
sities. All samples were those used for the analyses reported in the reference cited. LITERATURE CITED
(I) Ainsworth,
J*
77i 'I4
Am.
RECEIVED for review August 17, 1955. Socepted November 14, 19;;.
Determination of Equivalent Weights by Gamma Ray Counting of Iodine-1 31-Labeled Derivatives WILLIAM M. STOKES, FREDERICK C. HICKEY, O.P., and WILLIAM A. FISH Medical Research Laboratory, Providence College, Providence, R. 1. isemimicromethod for the determination of equivalent weights of compounds possessing certain functional groups involves the formation of derivatives of the unknown and of a known compound with a single sample of a reagent homogeneously labeled with iodine-131. The specific activities of the unknown and the known deritatives are determined by gamma ray counting of the crystalline derivatives. Equivalent weights of derivatives of the alcohols, amine, and acids studied agreed with theory within 2 q ~ .
T
HE development of high sensitivity gamma ray GeigerMdller counters of remarkable stability permits measureInents of considerable precision to be made on small samples labeled a t the tracer level ivith iodine-131. The successful use of gamma ray counting for the quantitative estimation of components of identical iodine-131 molar labeling on a chromatographic column ( I S ) suggested the possibility of determining equivalent weights of iodine-131-labeled derivatives by comparing the specific activity (counts per minute per milligram) of the derivative of an unknown compound with that of a known derivative prepared from the same homogeneous sample of iodine-131-labeled reagent. APPARATCS 4 S D PROCEDURE
A Model G. R. Welch-Allyn Texaco type Geiger-Muller gamma ray detector was enclosed on sides and top, except for an access hole to the well, by a shield of 0.5 inch of steel and 1.5 inches of lead. A removable lead plug was used to close the access hole during counting. I n this shield the counter had a background of npproximately 600 counts per minute. I n order to maintain constant source geometr a 1.5 X 4.75 inch polystyrene cylinder n machined to fit snugyi into the counter well. A 12-mm. axial hole was drilled down 67 mm. from the top and extended another 13 mm. at 6-mm. diameter. The cylinder was sawed along its axis from the top t o a point 53 mm. from the bottom. At this level a transverse cut wae made to the diameter, removing a
section to allow the small (6 X 20 mm.) glass-stoppered sample vials to be conveniently inserted or removed from the holder. This arrangement placed the samples on the center line of the N:ell and within the vertical limits of constant counting efficiency. An Atomic Instrument Co. No. 1050 scaler was used. It was fed from an electronically voltage-regulated source. Preliminary tests showed that the specific activity of a given sample a t relatively low counting rate, where coincidence was not a factor, was independent of the amount of material present (from 5 to 50 mg.), and of the type and weight of glass used in the sample vials (2 to 4 grams). The specific activity of the samples memured was between 2500 and 250 counts per minute per mg. in the counter described. R h e n possible, several samples were counted in succession and the series was repeated until approximately lo6 total counts had been accumulated for each sample. Though not essential, in one series the sample weights were adjusted so that the counting rate was approximately the same for all, thus eliminating the need for coincidence correction. The half life of iodine-131 was taken as 8.07 days (IO). A table was prepared of the values of the decay factor for each 5-minute interval from zero time. This is given by the expression D = No/Nt = antilog 2.5904 X 10-5 t (minutes) where N Oand N , are the total net counts per minute a t the start of the series and a t the mid-point of the counting period for each sample, respectively. Equivalent weights were calculated from the expression E , = E, ( & / A , ) where E , and E, refer t o the equivalent weights of the unknown and standard compounds, respectively, and A , and A , refer t o the corresponding specific activities in counts per minute per milligram a t the start of the series, as calculated from A = ( N - Nb) D / m where K and Nb are the total counts per minute of the sample and background, respectively, D is the decay factor referred to above, and m is the weight of the sample in milligrams. Samples were dried a t 60" C. in a vacuum oven for weighing. Specific activities were then calculated. As the equivalent weight is inversely proportional to the specific activity for samples derived from the same homogeneously iodine-131-labeled reagent, the equivalent weights of unknowns can be calculated if one substance in the series is known. REAGENTS
p-Iodobenzoyl chloride-iodine-131 was prepared for another experiment as previously described (IS). One week later 98.52 mg. of this p-iodobenzoyl chloride-iodine-131 were added to
