pyrazole - American Chemical Society

11 The Nitration of 5-Chloro-1,3-dimethyl-1H-pyrazole Risk Assessment Before Pilot Plant Scale-up Downloaded by STANFORD UNIV on February 18, 2015 | http://pubs.acs.org Publication Date: March 14, 1985 | doi: 10.1021/bk-1985-0274.ch011

JAMES R. ZELLER Pharmaceutical Research, Parke-Davis Division, Warner-Lambert Company, Holland, MI 49423

Reaction conditions which allowed for the large scale nitration of 5-Chloro-1,3-dimethyl-1H-pyrazole were developed which minimized the hazards generally associated with nitration reactions. Dilution with sulfuric acid decreased the risk of thermal instability. Using ordinary laboratory equipment, the experimental heat of reaction was determined to be -12.5 Kcal/mole. Likewise, the adiabatic temperature rise was found to be about 20°C. An exotherm was found to initiate at 100°C. The thermal stability and shock sensitivity of the product, 5-Chloro-1,3-dimethyl-4-nitro-1H-pyrazole, was investigated using simple tests.

The i n t r o d u c t i o n o f a r e a c t i o n t o the p i l o t p l a n t o f t e n proceeds w i t h o u t d e t e r m i n i n g the c h e m i c a l h a z a r d s i n v o l v e d w i t h the s c a l e up process. The reasons f o r t h i s v a r y . I n cases where a h a z a r d s e v a l u a t i o n l a b o r a t o r y i s n o t a v a i l a b l e , i t i s the r e s p o n s i b i l i t y o f the development c h e m i s t t o a s s u r e the s a f e t y o f the r e a c t i o n . The development c h e m i s t may n o t be f a m i l i a r w i t h hazard e v a l u a t i o n t e c h n i q u e s , and the i n s t r u m e n t a t i o n used t o e v a l u a t e a r e a c t i o n f o r s a f e t y may n o t be r e a d i l y a v a i l a b l e . I n o u r l a b o r a t o r y , we had the a s s i g n m e n t o f d e v e l o p i n g a p r o c e s s t o produce 10 Kg o f a p o t e n t i a l drug w h i c h r e q u i r e d the s c a l e up o f the n i t r a t i o n r e a c t i o n o f 5 - C h l o r o - l , 3 - d i m e t h y l - l H p y r a z o l e (CDMP, e q u a t i o n 1 ) . The n i t r a t i o n o f CDMP was o r i g i n a l l y c a r r i e d o u t on s m a l l s c a l e by m e d i c i n a l r e s e a r c h c h e m i s t s . U s i n g those same c o n d i t i o n s d u r i n g s c a l e up t o the 20 mole l e v e l , a l a r g e exotherm was observed l e a d i n g t o much foaming and l o s s o f p r o d u c t . Our g o a l was t w o - f o l d : (1) to develop n i t r a t i o n c o n d i t i o n s which would be s a f e upon s c a l e up; and ( 2 ) t o t e s t t h i s r e a c t i o n f o r s a f e t y ( 1^2). The s t e p s taken t o a c c o m p l i s h these g o a l s w i l l be described.

0097-6156/ 85/ 0274-0107S06.00/ 0 © 1985 American Chemical Society

In Chemical Process Hazard Review; Hoffmann, J., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1985.

Downloaded by STANFORD UNIV on February 18, 2015 | http://pubs.acs.org Publication Date: March 14, 1985 | doi: 10.1021/bk-1985-0274.ch011

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C H E M I C A L PROCESS H A Z A R D REVIEW

We were h e s i t a n t to work w i t h t h i s r e a c t i o n u n t i l we were c o n f i d e n t t h a t the n i t r a t i o n system d i d n o t possess a n a p p r e c i a b l e d e t o n a t i o n p o t e n t i a l . A l t h o u g h t h e r e a r e thermochemical computer programs a v a i l a b l e w h i c h c a n c a l c u l a t e the d e c o m p o s i t i o n p r o c e s s which y i e l d s the maximum energy r e l e a s e o f a system (3), we d i d n o t have such a program a v a i l a b l e . We t h e r e f o r e e s t i m a t e d t h e p o t e n t i a l d e t o n a t i o n energy o f the n i t r a t i o n system a s d e s c r i b e d by C h e s t e r G r e l e c k i o f the Hazards R e s e a r c h C o r p o r a t i o n ( 4^. B r i e f l y , t h i s t e c h n i q u e c o n s i s t e d o f b a l a n c i n g the c h e m i c a l e q u a t i o n o f the most p l a u s i b l e d e c o m p o s i t i o n r e a c t i o n , d e t e r m i n i n g the heat o f the r e a c t i o n , and c a l c u l a t i n g the TNT e q u i v a l e n c e . S i n c e the oxygen f u e l b a l a n c e f o r the r e a c t a n t s was c a l c u l a t e d t o be u n i t y (based on the r a t i o : Oxygen/(2Carbon + 1/2 H y d r o g e n ) ) , we c a l c u l a t e d the heat o f d e c o m p o s i t i o n f o r b o t h the oxygen r i c h case and the oxygen poor c a s e . I n the oxygen poor c a s e , the major c a r b o n c o n t a i n i n g p r o d u c t i s CO, and based on the s t o i c h i o m e t r y o f the r e a c t a n t s , the e q u a t i o n f o r the d e c o m p o s i t i o n o f the n i t r a t i o n r e a c t i o n may be w r i t t e n as f o l l o w s : C5H7CIN2 + 2 HNO3+ 2.3 H S 0 + 0.7 H 0 ^ 7 H 0 +5 CO + 2 N + 2.3 S 0 + HC1 2

4

2

2

2

2

T h e Δ H ( d e c o m p o s i t i o n ) was c a l c u l a t e d from the known Δ H f o f the r e a c t a n t s and p r o d u c t s , found i n a P h y s i c a l C h e m i s t r y t e x t 05). ΤηθΔΗ£ o f DMCP was e s t i m a t e d t o be 38.8 k c a l / m o l e by the CHETAH program (6). ΤηβΔΗ ( d e c o m p o s i t i o n ) o f TNT i n a n oxygen poor system i s -650 call g ( 40 , and the TNT e q u i v a l e n c e was c a l c u l a t e d as f o l l o w s : Δ H(decomposition) = Δ H f ( p r o d u c t s ) - ΔHf(reactants) -721 k c a l / m o l e - (-534 k c a l / m o l e ) -187 k c a l / m o l e T o t a l w e i g h t o f a 1 mole r u n = 494 g; -187/494 = -0.378 k c a l / g TNT e q u i v a l e n t = 378/650 o r 58.1% For the oxygen r i c h c a s e , the major c a r b o n c o n t a i n i n g p r o d u c t i s C0 , and the h e a t o f d e c o m p o s i t i o n o f TNT i s taken t o be -1100 c a l / g (4)· The e q u a t i o n f o r t h i s case may be w r i t t e n as f o l l o w s : 2

C H C1N 5

7

2

+ 2 HNO3 + 2 . 3 H S 0 + .7 H 0 ^ 5 H 0 + 4 C0 + 2 N + S0 + 1.3 H S + HC1 + CO 2

2

Δ

2

4

2

2

2

2

H(decomposition) = Δ H f ( p r o d u c t s ) - ΔHf(reactants) -790 k c a l / m o l e - (-534 k c a l / m o l e ) -256 k c a l / m o l e o r -0.518 k c a l / g TNT e q u i v a l e n t = 518/1100 = 47%


11.

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Nitration Risk Assessment Before Scale-up

109

Based on these r e s u l t s , we assumed t h a t the system possessed some thermal i n s t a b i l i t y , and our s t r a t e g y was to lower the h e a t o f decomposition o f the n i t r a t i o n system. D i l u t i o n o f u n s t a b l e systems tend to i n c r e a s e t h e i r s t a b i l i t y . C a l c u l a t i o n o f the heat of d e c o m p o s i t i o n , a f t e r d i l u t i o n w i t h 15 molar e q u i v a l e n t s o f s u l f u r i c a c i d ( v e r s u s 2.3 molar e q u i v a l e n t s i n the o r i g i n a l procedure) shows t h a t the p o t e n t i a l f o r e x p l o s i v e b e h a v i o r i s g r e a t l y diminished. This i s reasonable since s u l f u r i c a c i d decomposes e n d o t h e r m i c a l l y and i s n o t a n o x i d i z i n g agent. C H C1N 5

7

2

+ 2 HN0 + 15 H S 0 + 5 H 0 ^ 5 C 0 + 24 H 0 + 15 S 0 + HC1 + 2 N + 3.5 0 3

2


2

^H(decomposition) = Δ = = T o t a l weight of a 1 H(decomposition) = +

4

2

2

2

2

2

Hf( p r o d u c t s ) - Δ Hf ( r e a c t a n t s ) -2943 K c a l / m o l e - (-3294 K c a l / m o l e ) + 351 K c a l / m o l e mole r u n = 1835 g 191 c a l / g r e a c t i o n m i x t u r e

The thermal s t a b i l i t y o f the n i t r a t e d p r o d u c t , 5 - C h l o r o - l , 3 d i m e t h y l - 4 - n i t r o - l H - p y r a z o l e (CNP), was t e s t e d i n the l a b o r a t o r y by v e r y s i m p l e t e s t s . The p r o d u c t p y r a z o l e (0.1 gm) was p l a c e d on a hot p l a t e preheated to 300°C. The CNP melted and decomposed g i v i n g o f f a w h i t e smoke. Such r e s u l t s can be taken as n e g a t i v e . We i n v e s t i g a t e d the shock s e n s i t i v i t y o f the product by p l a c i n g a few c r y s t a l s on a s t e e l p l a t e and h i t t i n g the c r y s t a l s w i t h a c a r p e n t e r ' s hammer (JL) . A g a i n the r e s u l t s were n e g a t i v e . We p l a c e d a 6 i n c h s t r i p o f the compound on a watch g l a s s and i g n i t e d the compound w i t h a propane t o r c h . The m a t e r i a l burned v e r y r e l u c t a n t l y and s e l f e x t i n g u i s h e d a f t e r removing the t o r c h . There were no i n d i c a t i o n s o f e x p l o s i v e t e n d e n c i e s . F i n a l l y , we heated a 20 g sample o f CNP to 250°C. The o n l y a r e a o f thermal a c t i v i t y observed was near 75°C, the m e l t i n g p o i n t o f the compound. I n t h i s s e r i e s o f t e s t s , o n l y p o s i t i v e r e s u l t s would have been c o n c l u s i v e , w h i l e n e g a t i v e r e s u l t s d i d n o t prove t h a t the m a t e r i a l was s a f e t o h a n d l e . I t cannot be o v e r emphasized t h a t i f t h e r e were any i n d i c a t i o n s t h a t the p r o d u c t CNP was found to be t h e r m a l l y u n s t a b l e o r t h a t the n i t r a t i o n system c o u l d n o t be designed to be s a f e , a l l work would have been stopped on the p r o j e c t u n t i l more s o p h i s t i c a t e d a n a l y s i s (ARC, DSC, c a r d gap t e s t , e t c . ) i n d i c a t e d t h a t i t was s a f e t o c o n t i n u e our study. A t t h i s p o i n t , l a b o r a t o r y e x p e r i m e n t s were performed to tune the n i t r a t i o n r e a c t i o n f o r y i e l d and s a f e t y . We found t h a t n o t o n l y d i d excess s u l f u r i c a c i d lower the d e t o n a t i o n p o t e n t i a l o f the r e a c t i o n , b u t i t was a l s o b e n e f i c i a l f o r o t h e r r e a s o n s . Sulfuric a c i d i n c r e a s e d the r a t e o f the r e a c t i o n by i n c r e a s i n g the c o n c e n t r a t i o n o f n i t r o n i u m i o n s ; thus a l l o w i n g the r e a c t i o n t o o c c u r a t a lower temperature (30°C w i t h 15 molar e q u i v a l e n t s , v e r s u s 90°C w i t h 2.3 molar e q u i v a l e n t s ) where i t was l e s s l i k e l y t o e x h i b i t i n s t a b i l i t y . S u l f u r i c a c i d a l s o t i e d up the w a t e r i n the system, w h i c h i s known t o d e a c t i v a t e n i t r a t i o n p r o c e s s e s ( 7^), and a l l o w e d f o r the use o f 70% n i t r i c a c i d , w h i c h was e a s i e r and s a f e r to handle than 90 o r 95% n i t r i c a c i d . I t was found t h a t when the



110


b a s i c CDMP was mixed w i t h s u l f u r i c a c i d , a l a r g e amount o f heat o f n e u t r a l i z a t i o n was e v o l v e d . The m i x i n g o f 70% n i t r i c a c i d w i t h 96% s u l f u r i c a c i d a l s o e v o l v e d h e a t . P r e m i x i n g the p y r a z o l e w i t h one h a l f o f the s u l f u r i c a c i d , and p r e m i x i n g the n i t r i c a c i d w i t h the remainder o f the s u l f u r i c a c i d , removed these sources o f h e a t from the n i t r a t i o n system. These o b s e r v a t i o n s were i n c o r p o r a t e d i n t o the f o l l o w i n g n i t r a t i o n p r o c e d u r e . 5 - C h l o r o - l , 3 - d i m e t h y l - l H - p y r a z o l e (133 g, 1 mole) was d i s s o l v e d w i t h c o o l i n g i n 96% s u l f u r i c a c i d (686 g, 7 m o l e ) . T h i s s o l u t i o n was added, m a i n t a i n i n g a temperature o f 30°C, t o a s o l u t i o n o f 70% n i t r i c a c i d (177 g, 2 mole) i n 96% s u l f u r i c a c i d (784 g, 8 m o l e s ) . The r e a c t i o n was s t i r r e d f o r 20 minutes, poured onto i c e w a t e r , and the p r o d u c t was c o l l e c t e d by f i l t r a t i o n . Only s l i g h t c o o l i n g was n e c e s s a r y f o r m a i n t a i n i n g the 30°C r e a c t i o n temperature, and t h e r e was no e v i d e n c e , such as d i s c o l o r a t i o n o r b u b b l i n g , t o suggest t h a t d e c o m p o s i t i o n had o c c u r r e d . I t was t h i s system which we d e c i d e d t o t e s t f u r t h e r f o r thermal i n s t a b i l i t y . I n i t i a l experiments conducted to t e s t the thermal s t a b i l i t y o f the n i t r a t i o n r e a c t i o n were d e s i g n e d t o determine i f exotherms o c c u r r e d a t e l e v a t e d temperatures. Behind a b a r r i c a d e , we r e m o t e l y heated about 6 grams o f the n i t r a t i o n r e a c t i o n m i x t u r e i n a s i l i c o n e o i l b a t h to 260°C w h i l e r e c o r d i n g the temperature o f the b a t h , the temperature o f t h e sample, and n o t i n g any o b s e r v a t i o n s . ( T a b l e I ) . We observed a n exotherm i n i t i a l l y (from the h e a t o f the n i t r a t i o n r e a c t i o n ) and a n o t h e r exotherm a t about 100°C. T h i s i n i t i a l experiment was r e p e a t e d u s i n g t h r e e d i f f e r e n t CDMP charge r a t i o s ( 3 3 , 5 0 , and 66% mole r a t i o s ) t o r e p r e s e n t the r e a c t i o n d u r i n g the a d d i t i o n p r o c e s s . The thermal b e h a v i o r d i d n o t d i f f e r s i g n i f i c a n t l y from the o r i g i n a l c a s e , where the f u l l molar e q u i v a l e n t o f the CDMP was p r e s e n t .

Table I .

Time (min.) 0 5 10 15 20 30 40 45 50 55 60 65

Open T e s t Tube Thermal S t a b i l i t y T e s t Temp. Bath

Temp. Sample

(°c)

(°c)

24 25 26 26 27 73 128 148 163 175 213 233

24 32 33 29 27 53 110 135 157 170 184 218

Τ 0 +7 +7 +3 0 -20 -18 -12 -6 -5 -29 -15

Observations Added CDMP

I n i t i a t e d heating

Bubbling noticed More b u b b l i n g Brown Fumes Fumes s t o p H e a t i n g stopped



11.

ZELLER

111


Knowing t h a t e x o t h e r m i c a c t i v i t y d i d e x i s t , i t was now n e c e s s a r y to f u r t h e r d e f i n e the temperature o f i n i t i a t i o n o f the exotherm u s i n g a system w h i c h approximated the n e a r a d i a b a t i c con d i t i o n s found i n a j a c k e t e d 50 g a l l o n r e a c t o r . We c o n s t r u c t e d a c a l o r i m e t e r c o n s i s t i n g o f a 250 ml 3-neck round bottom f l a s k immersed i n a s i l i c o n e f l u i d b a t h , a l l c o n t a i n e d i n a dewar f l a s k (1^, F i g u r e 1 ) . The temperature o f the b a t h c o u l d be i n c r e a s e d by use o f a Nickel-Chrome w i r e h e a t i n g element connected t o a v a r i a b l e power s u p p l y . Both the temperature o f the b a t h and the sample were r e c o r d e d on a d u a l pen c h a r t r e c o r d e r . Both the b a t h and the sample were s t i r r e d . A 150 ml sample o f the n i t r a t i o n m i x t u r e was heated a t a r a t e o f 3°C/min. and the f i r s t exotherm was n o t e d t o b e g i n a t 100°C. T h i s exotherm peaked a t 183°C a t w h i c h p o i n t the temperature o f the sample was 12°C above the temperature o f the b a t h . Another exotherm was observed s t a r t i n g a t 220°C and peaked a t 270°C where the sample temperature was 14°C above the temperature o f the b a t h ( F i g u r e 2 ) . No thermodynamic data c o u l d be o b t a i n e d from t h i s e x p e r i m e n t s i n c e gases were a l l o w e d to escape and the exotherms were p r o b a b l y moderated by t h i s slow endothermic v a p o r i z a t i o n . N e v e r t h e l e s s , i t was v e r y i m p o r t a n t t o know t h a t i f the temperature o f the n i t r a t i o n was a l l o w e d t o approach 100°C, we c o u l d e x p e c t e x o t h e r m i c b e h a v i o r . We t h e r e f o r e had to a s s u r e t h a t the r e a c t i o n temperature c o u l d n o t r e a c h 100°C. The temperature r i s e o f a n e x o t h e r m i c r e a c t i o n i s dependent on three f a c t o r s : the heat o f the r e a c t i o n , the h e a t c a p a c i t y o f the system, and the h e a t l o s s o f the system. The temperature r i s e o f a r e a c t i o n i n a system w i t h no h e a t l o s s , the a d i a b a t i c temperature rise (Δ ) > dependent on the h e a t o f the r e a c t i o n and the h e a t c a p a c i t y o f the system, and independent o f s c a l e . To d e t e r m i n e the a d i a b a t i c temperature r i s e o f t h i s system, the C D M P / s u l f u r i c a c i d s o l u t i o n , prewarmed to 30°C, was added a l l a t once to a dewar f l a s k c o n t a i n i n g the n i t r i c a c i d / s u l f u r i c a c i d s o l u t i o n w h i c h was a l s o prewarmed t o 30°C. We observed a temperature r i s e o f 17°C o v e r a p e r i o d o f 4 m i n u t e s , w i t h a temperature drop o f 1.5°C o v e r the n e x t 4 minutes ( F i g u r e 3 ) . We t h e r e f o r e e s t i m a t e d the Δ be about 18.5°C. S i n c e t h i s temperature r i s e was, i n t h e o r y , independent o f s c a l e , we c o u l d p r e d i c t t h a t the l a r g e s c a l e n i t r a t i o n r e a c t i o n would n o t r i s e to a temperature o f e x o t h e r m i c a c t i v i t y . Based on these r e s u l t s , we c o n s i d e r e d t h i s r e v i s e d n i t r a t i o n p r o c e d u r e to be s a f e upon s c a l e up t o the p i l o t p l a n t . A t t h i s p o i n t , we r e t u r n e d to the o r i g i n a l n i t r a t i o n procedure ( w i t h 2.3 molar e q u i v a l e n t s o f s u l f u r i c a c i d ) t o t r y to determine why the n i t r a t i o n was n o t s a f e upon s c a l e up. The /\,T f o r t h i s o r i g i n a l p r o c e d u r e c o u l d be c a l c u l a t e d from the h e a t c a p a c i t y (Cp) of the system and the h e a t o f the r e a c t i o n ( /\H) by the e q u a t i o n ΛΗ = Cp χ Λ Τ . The h e a t c a p a c i t y o f n i t r i c a c i d / s u l f u r i c a c i d / water systems a r e a v a i l a b l e (8) and found to be 678 c a l / m o l e °C (assuming t h a t the h e a t c a p a c i t y o f the CNP/CDMP component was negligible). U s i n g the e x p e r i m e n t a l l y d e r i v e d temperature r i s e , the heat o f the n i t r a t i o n r e a c t i o n was e s t i m a t e d t o be: τ

i

s

τ

ΔΗ

= =

t

0

(18.5°C)(0.678 K c a l / m o l e °C) 12.5 K c a l / m o l e



F i g u r e 1 - Diagram o f the c a l o r i m e t e r used i n the a d i a b a t i c thermal s t a b i l i t y s t u d i e s .



ZELLER


Time

(min)

F i g u r e 2 - The e x p e r i m e n t a l d i f f e r e n t i a l temperature c u r v e o b t a i n e d from the a d i a b a t i c thermal s t a b i l i t y s t u d y .

F i g u r e 3 - Temperature c u r v e o b t a i n e d d u r i n g the a d i a b a t i c temperature r i s e s t u d y .


113


114

(8).

The heat c a p a c i t y of the o r i g i n a l procedure was 140 c a l / m o l e °C The a d i a b a t i c temperature r i s e was then c a l c u l a t e d to be: T


12.5 k c a l / m o l e = ( A > (0.140 K c a l / m o l e AT = 89°C

°C)

The r e a s o n the o r i g i n a l procedure was n o t s a f e was then e v i d e n t . The o r i g i n a l r e a c t i o n was c a r r i e d o u t a t a temperature o f 90°C, w i t h o u t c o o l i n g , and the heat o f the r e a c t i o n drove the r e a c t i o n temperature i n t o a r e g i o n o f e x o t h e r m i c a c t i v i t y , r e s u l t i n g i n a runaway r e a c t i o n . The g r e a t e r h e a t c a p a c i t y of the r e v i s e d system, due to the excess s u l f u r i c a c i d , absorbed most of the h e a t o f the r e a c t i o n , p r e v e n t i n g the r e a c t i o n temperature from r i s i n g to a dangerous l e v e l . I n summary, we determined through s i m p l e thermodynamic c a l c u l a t i o n s t h a t a p o t e n t i a l s a f e t y problem d i d e x i s t , and how to d i m i n i s h t h i s problem by the a d d i t i o n of excess s u l f u r i c a c i d . We i n v e s t i g a t e d the e x o t h e r m i c b e h a v i o r o f the r e v i s e d n i t r a t i o n u s i n g common l a b o r a t o r y equipment, and found t h a t an exotherm d i d o c c u r i n i t i a t i n g a t 100°C. We determined the a d i a b a t i c temperature r i s e to be l e s s than 20°C w h i c h would i n s u r e t h a t the n i t r a t i o n r e a c t i o n , p r o p e r l y b a t c h e d , would n o t approach a temperature o f e x o t h e r m i c a c t i v i t y . F i n a l l y , we e x p l a i n e d the reason f o r the thermal i n s t a b i l i t y o f the o r i g i n a l p r o c e d u r e . Of c o u r s e , the r e v i s e d n i t r a t i o n r e a c t i o n i s n o t f r e e of hazards a s s o c i a t e d w i t h human e r r o r o r equipment f a i l u r e . It is i m p o r t a n t to note t h a t a t P a r k e - D a v i s , we r e c o g n i z e t h a t the p e r s o n most f a m i l i a r w i t h a p a r t i c u l a r r e a c t i o n i s the development c h e m i s t . T h e r e f o r e , the development c h e m i s t a c t u a l l y c a r r i e s o u t the r e a c t i o n i n our p i l o t p l a n t , and he o r she can b e s t r e c o g n i z e when a hazardous s i t u a t i o n a r i s e s . Work i s c o n t i n u i n g on t h i s r e a c t i o n to f u r t h e r decrease the r i s k i n v o l v e d . P r e l i m i n a r y r e s u l t s u s i n g one molar e q u i v a l e n t o f n i t r i c a c i d v e r s u s CDMP l o o k p r o m i s i n g . Acknowledgmen t The a u t h o r wishes to acknowledge Mr. C h a r l e s Combs f o r h i s c r i t i c a l d i s c u s s i o n s d u r i n g the c o u r s e of t h i s work. Literature Cited 1.

2. 3. 4. 5. 6. 7.

8.

Fawcett, Howard Η., Wood, William S. "Safety and Accident Prevention i n Chemical Operation"; Wiley: New York, 1965; Chap. 19. Coffee, R.D. Loss Prevention 1969, 3, 18. Van Dolah, R. W. Loss Prevention 1969, 3, 32. Grelecki, C. National Safety Congress Transactions 1973, 5, 22. Castellan, G. W. "Physical Chemistry Second Edition"; Addison -Wesley: Reading, Mass., 1971, p. 137. P f e i f f e r , C., personal communication. De La Mare, P. B. D.; Ridd, J . H., "Aromatic Substitution: Nitration and Halogenation"; Butterworth: London, 1959, Chap. 5. Perry, P. H.; "Chemical Engineers' Handbook"; Magraw-Hill: New York, 1973, p. 3-205.

RECEIVED November 14, 1984 In Chemical Process Hazard Review; Hoffmann, J., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1985.

pyrazole - American Chemical Society

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