May 31, 1976 - ... upon infrared analysis. 0. 0. R _. R- N K D if - ... Ritter et a1 7 reported the reaction of nitriles
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SECRET U. S. Army Chemical Research and Development Laboratories
Cq
Technical Report
cmn
S Sr _
by
Brennie E. Hackley, Jr. Chappelle C. Cochrane Ethel B. Hackley
C1il
LnJ
May 1964
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l~r!!
CRDLX 3213
May 1964
SOME CHEMICAL REA.CTIONS OF BZ (U)
by
Brenwia Z. Hackley. Jr. Ckhsppet-le C. Cochran~e -%'helS
Hackley
ftecc~ri eidirig Approv.ak
Colonel, MC Dvrector of Methmal Regearch Approved:
S. D. ShI.VZ Tec~ncal~ Direttor
U. S. Army £dSevmod Arsenal CHEMICAL aR=AftCH AND DEVZLOPMiE4T LABOkATORILS Vdgewood ArsenAl. Marylanid
AMET
U14CLAID (U)
FOREWORD
This work wat conducted under Tatk 4Z08.03-016-;4. Biochemical Action of Chemical Agents JU). The experimental data are contained in notebooks MN-145Z, M24-1465. MN-1440, MN-1400.and MN-IS87. TI. completed ir. April 1962. work was started in March 1961 &Mad Ackncvledgtments The authors wish to ackntmledg. the technical assistance uf Messrs. David E. Ronard. CI~ford ShIblom, 1Renneth E. Stine. and Robert L. Green. Notic eo This dociment contains informatton affecting the rAtional defenee of the United States witin the mearing of the tqponsge Laws. Ttle I .. U. S. C.. sections 793 a-d 794. The transmission or the rbvelrtion of its contents in any manner to a.n unauthoruzed person Is robh ittd by law. Reproduction of tats document in .hole or part is prohibited except with the pernision of the issumg office; hswever. DDC is authoried to reproduce the dcunent for U. S. Go'ernment1 p,,rp'.ses Disposition When this document has served its purpose. DESTOY tt i, DO NOT retturn the documet to U. S. Arr y acccrdance with AR 380-5 Laborttoriev. Development and Research Chemical
UNCL_5-1| |..
|
CONFIDENTIAL (C)
DIGEST
A fundamntal study of the cheminstry of 13Z wra condt-~te'd to assist in prob'sens tih&t may zrite in detecuon. dtvontasmialion. biochgtirmechanism of 3etion. and metaboism. BZ reicts *-2t~n (a) *ubstituspd pbenYI %&ocyanates Wo ysild 2. 4-oaaolinedionet. (b) nitriles to produ~ce a-rIded Wsat (Ritter reaction). "it (c) alkyl )halades to give "~teronary amonist Analysis of LIZ can he accompUshed by quattrnizatiotm iu acetonitrile separation of reactan~ts. and &*saying asectral~
CONFIDENTL 3
SECRIET SOME CHEMICAL REACTIONS5 OF BZ (U)
IS) (S)
INTRODUCTION
(U) 8. is a crimpound that has be*-n ty~pe ctassified as an irm.apacitating chernical agent To assist in the evaluation ot the biological properties of the agent- -adprobtemns of m.-nufacture, storage stability, detection, de.. -iftanin~ation, bioch-emin~ mechantisni of action, and metabahtsr. a fundam,* tat otzdv of the chemist"i of 13Z has been m~ade. IS) snes:
Ia)
In thi- chemicAl structure of BZ there arre three primarf 7eactiv'e the tetazv 0io.l() the estzr linkage, and (c) the quinuclidinyt
0P
nitrogen atom. A surv-:y of the literature (open anid classified) on benilate esters '.orainlrag a tertiary nitrogen .t !hew A-pos.-Oon of the alcohol moietyl. 2, 3.4 shows that most attention has been directed to reactions 1! the tertiary nitrogen, i. e.. quaterruzztioln and salt formation, while little has been done art the direct reactions of the hydroxyl function A considerable effort has been expended in these Laboratories on the hydrolytic cleavage of BZ. The purpose of this rese'arch was to study reActio:%s of the tertiary hydroxyl group as *ell as reactions vpecific for benzilate esters that invi 'e a bi functional az two centered attack on The alcohol and ester linl~age. lot addition. s$%)Me previously unreportedi qua ern-iTy salts wbere prepared as model.- to assist in the analysis anid tdentaication of BZ and its metabolic products 11
(S)
PROCEDUPLr AND RESULTS.
A,
(S)
Z, 4- Oxsolildirtediones.
One of the clsasic modes of formation of 2.4-oxazolidinediones (5) results from the teact;an of an .- hydr-5xyesterand an isocyanate to foem the
SECRET corresponding urethane, which is subsequently cyclized by heat or alkaline catalysta to the requsatte oxazolidinedione. 5
0 1I
0
RCH-C-OR'
I
OH
R"NCO -
0 _i
R-CH-C-OR---30R-CH
I
0
NH-R"
C II
0
I
_,4
3-
'
Cs 4 0
0 (S)
In the special c~ase of benzilate esters, the oxazolhdinedioties are formed spnntaneously, even at low temperatureson reaction with an irecvanate. 6 This type of two-centered attack would b- specific for benzilate esters such as BZ. By judicious selection of the isocyanate. the N-subtttuted-5o 5-diphenyl oxazolidinedione (obtaintd as a single product) coul" possibly be analyzed by iluorescent, colorimetric. infrared, or other physical
C/ C \c-L-o~QRNC
/ __ / O VNQ
at.alytical means that would provide an uneqWiv.2cal assay of the benzilate to the total exclusion of other metabolic fragments. I.
(U)
General Procedure for the Preparation of Oxasolidinedionet From 8Z.
A mixture of ) gm (0.003 mole) of Z. 0.003 mole of iocyanate. and 10 ml of dry benzene was refluxod for 1 hr. The cooled benzene solution *as filtered and the filtrate evaporated to dryness under vacuum. The residue crystallized from isopropyl alcohol afforded the oxasolidinedione
6
(U)
2
Results.
The oxazoldinediones prepared are listed si table I exhbxit character,.a.,i and 5. 7p (amide). D
(S)
They all
infrared absorption% in the regions of 5. Sp (urethane)
Ritter Reaction Products
7 alk,.nes or Ritter et al reported the reaction of nitrtleb with (S) tertiary of presenct The amides tertiary akohoI4 to form 14 t-alkyl to BZ. reaction this of application possible the alcohol group in BZ suggested
I
(U)
General Procedure lor the Ritter Rection.
nitrle A solution of I 3m (0.003 mo!e) of BZ and 0.004 mote of conof w.1 I5 and bath ice an in in 10 ml of glactal acetic acid was chilled temiw.awre the that such rate a at centrated sulfuric acid added dropwise was stirred cold %wasmaintained between 5 to FO C. The reaction mixtre poured onto was solution The hr Z for temuperature for I hr and at room soluiton. t1en crushed ice and neutralized with saturated potassium carbonate potasatun extracted with rbloroform, The extract was dried over anhydrous was residue The carbonate or sodium sulate and the solvent removed. 0 ° C to 6O to 30 (bp ether c rystalliced from benzene or benzene patroleum yield the desired produc, Z
()
Results
Table 2 lists the Ritter products prepared
They are colorless,
show no unusual charactercrysaailine solids with definite melting points and
istit absorptions upon infrared analysis
R_N
R0
KD
0
I-
if-
0
70
Sam
Iii o
4
O4C 4
_
~.. 0 ~
0
_
~
_
C
'0
_W_
m
an
-i
A
4
-
2 IAft~
0z OWf _
-
j
~
zo
A . .0?-L
=
0
_
0-
9 -
w.
_
_ _
0~
_
S. -
0A
fm
N
-
A
SECRET Z
(U)
Results
The oxazobdirediones prepared are listed in table I They all exhibit .haracteristic infrared absorption% in the regions of 5 51& (urethane) and 5. 7p& amide). B
S)
Ritter Reaction Products
(SI Ritter et a1 7 reported the reaction of nitriles with als,,.net or tertiary alcohols to form N -alkyl amides The presence rf %tertiary alcohol group in BZ suggestrG; the possible application of this reaction to BZ. I
(U)
General Procedure for the Ritter Reaction.
A solution of I gm (0 003 moe) of BZ and 0.004 mole of nitrile in 10 iml of glacial acetic acid was chilled in an ice bath and I ml of concentrated sulfuric acid added drowise at a rate such that the te was maintained between 5 to 10 C The reaction mixture wa, stirred cold for I hr and at room temperature for 2 hr The soluti-n was poured onto crushed ice and neutralized with satura,.ed potassium carbonate solution, then ektracted with chloroform. The extract was dried over anhydrous potassium carbonate or sodium sulfate and the solvent removed The resiaue was crystallized from benzene or bcnzen,. petroleum ether (bp 300 to 60 0 C) to yield the desired prodts Z
-
IS)
Results
Table 2 lists the Ritter products prepared They are colorless. crystalline solids with deftnite melting points and show no unusual charucteristic absorptions upon infrared analysis
0
C-C-Q
0
-4C-C--1
0\/
o ,
KIII)\0
0
l'r 1111" 1!111 ' SERE
UNLAMMD Io
*
.0
0
r-
0
I
*0
I
C
u.
*
04U
V
0
fq
-
0=
0
0m
s-s
O=U ON
Q
:c__ ON
u UNA*IFE I.9
=U u
=U I
0--
I
efI
SECRET C.
I", Quaternary Ammonium Compou.s.
(C) Wh-n a tertiary base is quaternized with an alkylhalhde. the differences in solubility of the salt-like product and the startnX materials should be sufficient to &llow spectral determination of the base. Several substituted phenacyi bromide quaternaries of BZ were prepared I
(C)
General Procedure for Prepration of Quaternar
Salts. A mixture of I gm (0.003 mole) of BZ, 0.004 mole of the phenacyl bromide. and ?5 ml of chloroform was allowed to stand at room temperature for IS hr. The solvent was removed under vacuum and the residue was crystallized from ethanol-ether. acetonitrile-ether, or ethanol- 1,2 dimethoxyethane. ts)
Z.
Results.
These products, typical high-melting crystalline solids. are listed in table 3
o0 a
0
R-*-C-CHAX,.
OH1 D.
(C)
-.
-c/RC
X OHO0 -. C,,c o
x
bZ Acetate.
As part of this overall program, the authors were interested in preparing the ac.lated der:vatives of BZ. In this connection attempts were made to acetylate BZ with acetic anhydride and wth acetyl chloride ia pyridine to no avail. The infrared spectrum of BZ indicates strong intramolecula.. vr intermolecular hydrogen bonding, which is absent in its %salts. The tionreactivity observed with the usual acetylating reagents may be due to this bonding as well as to steric factors. Thus, treatment of the p-toluentsulfonic acid *Idt of BZ with 3sopropenyl acetate afforded the acetate quite smoothly.
SECRET 10
COMFIENTIAL TABLE I
(C)
PHENACYL BROMIDE QUATIRIHARY SALTS OF BZ (C)
I Alkyl halide
Melting point
Carbon eld
9Z
68 68
p-Nstrophencvl brow de 190-191 p. Brcmnophenacl br.mde 170-175
99 90
S9.9 56.6 7.7
(Z0-2?4
en
" CalculatedFoud Cac;ua.,ed F-und
p-Phenylphercyl broaride 214-ZIS
is Naphthacv1 bromide
flyd
931
168 9
158. 3 S6 61
16i
5.
S.7
5 1 4.8
5 3 4 8
S
5.4
A mixture of Z gm 10 0039 mule) of the p-tolhenesulfoniw arid salt of BZ. mp 1800 Uo 182 0 C. 20 ml of isopropenvl acetate and a few crystals of p-toluenesulfonic acid was reiluxed; acetone was distilled off slowly over a period of 5 hr. The riature was homogeneous at this time. The excess asopromenyl acetate woas removed under vacuum and the residue made alkaline with coid saturated potassium carbonate solution. This was extracted with chloroform, dried over anhydrous sodi.:n sulfate. and the solvent removed The residue was refluxed with diethyl ether. filtered. f-ider reduced pressur, and cooled to room temperature. :t yielded 0 05 gm. 44 5%, of the acetate. mp 121 ° to lZ30 C. Cal colat#d: C. 71. 8; H, 6 b Found. C. 72. 7 H. b 7 E.
(C)
Spectrophotometric Determination of Small Quantis;es of BZ
p-Brc-mophenacyl bromide reacts readily with BZ in acetonitrile forming a quaternary salt. Since quaternarv salts have re)Atvely high solubsity inwater.one may separate the product from reactants and thus determine the amount of tertiary amsne originaliy present. A plot of absorbancy versus concentrat:on foilows Beer's law. Detailed procedures for the determination of BZ in (a) acetonitr le. (b) water. and (c) in human whol* blocd follow.
CONFDETIAL Ii
CON4.0FIDENUiAL Recrystallized p-br.ziophenacyl bromide. spectrc, CP. 0 I N ris(hydroxy,-thyl)aminomethanc
Reaents: grade acc-.*i'e. (tris) buffer (p11 S. 5). I
cyclohexane.
and BZ.
Determinauon of BZ in Actetonitrile.
(C)
To 0. 1 ml of 10-? M solution of p-bromophenacyl 1,romidc in (C) acetonitrile in a glass-stoppered bottle is added I to -10 ug of LZ dissolve, The solution is mixed and heated in a 5(0C w:..r in I ml of acetonitrile. Z ml of After cooling the solution to room temperature bath tor 10 min 0. 1 St KCI and 5 ml of cyclohexane are added and the mixture is mechanically shaken for 5 min. A portion of the aqueout phase is read spectrophotometrically at 265 mu and the adherence to Beer's law demonstrated (table 4,
figure 1). (U)
TABLE 4
DETER?&NATICN Of 1%Z IN ACETONITRILE
Absoroancy*
BZ '~~~~~g mlI
Jll•
I
0 .b 5.Z 7. F.
10.4
j
13.0
l
O.066 O.Z05 . Z8 0.456 0.597
0.738
Average of five determinatiuns Z.
(C)
Determination of BZ in Aqueous Solutions.
To 2-ml aqueous solutions of BZ (5 to 40 ug) are added 0. Z ml (C) of tris buffer (pH 8.5) and 3 ml of chloroform. The mixture ts shaken mechanically for 5 min and the aqueous layer removed. An aliquot of the chlotolorm layer is air evaporated and the residue dissolved in I ml of acetonitrile. The analysis is then made in the manner reported above (E. 1.) (table 5. figurt Z1.
CO'VFI
,.:__.,!, !!! ''l'"1
NIAL
1.01
I 0.,
0.4
0. t
*0.1
.1
0.13
CONFIDENTIAL TABLE 5
(U)
DETERMINATION OF BZ IN AQUEOUS SOLUTIONS
BZ
Absorbancyz
ugiml
T 0--O.
mi m
i
sh
t
0.6Z 1.2 5 5 s0
0 018 0s058 0. 0lo 0 53
7.5 10.0 Iz 5
O0 391 O, 517 0 ,6'4o
Average of five determinations 3.
i
I(c
~BZ. ~form
(C)
e
n0
Determi~natio~n of 3Z in Huantan Whole Blood.
To I ml of human whole blood is added a 1-ml aqueous solution of
The mixture is diluted to 7 ml and th-oroughly mixed. Onj millilitur of 50% ZnSO 4 is added. mixed. and followtd by I -nt of 0. 3 N Ba(OH)Z . Chloro(10 ml) is added and the mixturr is shaken mechan~ically for 10 rmin. It is then transferred to a glass -stoppered centrifuge tube and spnn at Z500) rprn
for 10 min. A 4-ml aliquot of the chloroforr. layer is air evaporated and the analysis performed in acetonitrile as above (tabie 6. fi-are 31. TABLE 6
(U)
DETERMINATION OF BZ IN WHOLE BLOOD
Absorb ancy'
BZ uglml 1 7 3.4 5,1 5.9 6.8 8 5 10.2 *
!! [
1
0 062 0 148 0 Z30 0.Z80 0.317 0.388 0.478
Average of four determirstions.
CONFIlENTAL 14
UNCLASSWD
09
0.S
0.7
0o4
0. 1
0
~~
4
!I MI~t~gw
. pew
i1.
zr.
21
14
ouis
AtN<S1S Of 8Z V4 AQUW:US SOLUTIONS
is
16
UNCLAS5IED
.Si
*0.4
0.3
0.3
mikt"vam.e lit
millntow (imai 9a1OMuI
FIGURE 3 AI4ALYSIS OF BZ IV. BLOOD
16
CONFIDENTIAL III.
(C)
CO14CLUSIONS. A fundamental study of the chenstry of BZ was conductee to
assist in problems that may at izc in detection, decontamination.
biochem.cal mechanism of action. arid netabolism. BZ reacts with (a) &ubstltutee phenyl i.ocyaaatet to yield 2,4-oiazolidinediones. (,b)nitriles to produce awrstdes (Ritter reaction), and (c) alkyl halides to give quaternary ammonjurr -- ilts. Analysis of BZ can be accomplished by quaternmzation in acetonitrile, teparation of reactanto, and assaying spectrally.
CONFIDENTIAL
UNCLASSIFIED (U)
J. Che.--
LITERATURE CITED
Z.
Sternbach.
L. H..
Synthetic Mydriatics.
and Ing. H. R.
Ford-Moore, A. H., I. Soc. (London) 55 (1947).
ar4 haiser. S.
Antispasmodics III
Esters v, Bicyclic Alcohols ad Their Quiternary Salts. 75. 6068 (1953).
J. Am. Ch-
..Soc
3 Sasq. Samuel. Master. Irwin.Ltudemann. William D., Martin. Johi. I Bratt. Martin. Sp-4. and Matoushek. Ralph. PFC. Technical Memorandum 1 3-14. Colorimetric and Spectrophotometric Estimation of EA 2277 and Similar Compounds. Some Chemistry on the Decomposition of EA Z277 (U) June 1960 SECRET Me-rv.'-1ui 4 U. S. Army Chemical Research and Devilopmert Laboratories. CRDL Special Publication 4-28 EA Z277 (U). A 5-,'."'n Report as of 15 March 1961 March 1961 SECRET Report. 5 58. 63 (1955)
Clark-Lewis. 1. W,
6 Rekker. R. F.. Verleur. H.. and Nauta. W T%. 7,
Ritter. I..
2.4 Oxazolidinedione
Faber. A. C.. Tom. D. H. E., Rec. zrav chim 70. 1ld (1951).
and Kalish. I
J. Am
4048 (1948).
UNCLASSIFIED 19
'C
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Chem
Cheax
Soc
70,
ry
Revs
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108 109
5 (Contd)
Director. Biological Sciences Division (Code 440). Office of Naval Resedrch. Departmen, of the Navy. 17th At C~nstitutioi Avenue. N. W.. Washington Z5. D. C. Director of CBR Operations. Office of the Assistant Chief " Staff for Force Developments. Dept of the Army ATTN: FOR CMSR. Washington. D. C. - Z0310 Director of Engineering & Industrial Services. ATTN: Publications Clerk. U. S. Army Edgewood Arsenal, Edgewood Arsenal. Maryland - Z1010 Director. U. S. Army Edgevood Arsenal. Operations Research Group. Edgewood Arsenal. Maryland- Z1010 Director. U. S. Naval iF4tcearch Iaboratory, ATTN: Army Liaison Officer. Code 1071. Washington. D C. 20390 Director. Walter Reed Army Institute of Research. D" json of Neuropsychiatry. Washington. D. C. - Z001± Director, Walter Reed Army Institute of Research. Walter Reed Army Medical Center. Washington. D. C. - Z0012 Division of Health Mobiliaation. U. S. Public Health Service. ATTN: Mr. Charles H. Harp. Deputy Chief. Research Branch. Romn 1±16. Tempo 'R" Building. Washington Z5. D. C. Dr D. F. Downing. Defense Rearth Staff. Munitions/TW. British Embassy. 1100 Massachusetts Avenue. N. W. Washington S. D C. Executive Director. EA CBR Advirory Council. Room Z7Z. Building 5101, Edgctood Arsenal, Maryland - 21010 Headquarters. AFLC (MCD). Wright-Patterson AFB. Ohio45433 Headquarters. AFMTC. Deputy for Bioastronautics (MTX). ATTN: Col. William H Lee. USAF. MSC. Patrick Air Force Base. Florida - 3±925 Headquarlers. AFSC (SCGB). ATTK. B. E. Flaherty. LI. Col.. USAF. MC. Andrews Air Force Base, Washington, D. C. Z0331 Headquarters. U. S. Army Cmbai Developments Command Comnbt Service Support Group. Fort Lee. Virginia - Z3gAI Headquarters. U. S. Army Munitions Command. Marine Corps Repre~er.tative. ATTN: AMSMU-LM. Dover, New Jersey -
07801 110
Hq. U. S. Air Force. (AFMSPA-Bionucleonics). ATTN: Special Weapons Defense Officer). Washington, D. C. - Z0333
IIlil e !r 'r!,1 ~~UNLllAFlM
DISTRIBUTION LIST NO
89 90
V 1-19Z
93 94 95 96 97
98-103
104 105 106
107
106 109
5 (Contd)
Director, Biological Sciences Division (Code 440). Office of Naval Research. Department of the Navy. 17th & C3nstitution Avenue. N. W.. Washingtor. Z5. D. C. Director of CBR Operations. Offic e of the Assistant Chici - Staff for Force Developments. Dept of the Army ATTN: FOR IMSR, Washington. D. C. - Z0310 Director of Engineering & Industrial Services, ATTN: Publications Clerk. U. S. Army Edgewood Arsenal. Edgewood Arsenal. Maryland - 1010 Director. U. S. Army Edge.ood Arsenal. Operations Research Group. Edgewood Arsenal. Maryland- Z1010 Director. U. S. Naval Research Laboratory. ATTN: Army Liaison Officer. Code 1071. Washington. D C. Z0390 Director. Walter Reed Army Inststute of Research. Dit-:in of Neuropsychiatry. Washington. D. C. - 1001Z Director. Wtlter Reed Army Institute of Research. Walter Reed Army Medical Center. Washington. D. C. - Z002Z Division of Health Mobilization. U S Public Health Service. ATTN- Mr. Charles H. Harp. Deputy Chief. Research Branch, Room IZ16. Tempo "R" Building. Washington Z5. D. C. Dr D. F. Downing. Defense Reseat ch Staff. Munitions/TW. British Embassy. 3100 Massachusetts Aicnue. N. W. Washington 8. D C. Executive Director. LA CBR Advisory Council. Room Z7Z, Building 5101. Edgewood Arsenal. Maryland - ZI010 Headquarters. AFLC (4?CD). Wright-Patterson AFB. Ohio45433 Headquarters. AFMTC. Deptity for Bioastronautics (MTX). ATTN: Col. William H Lee. USAF, MSC. Patrick Air Force Base, Florida - 3Z9Z5 Headquarters, AFSC (SCGB). ATTN. B. E. Flaherty. Lt. Col., 1.SAF. MC. Andrews Air Force Base, Washington, D. C. Z0331 Headquarters, U. S Army Combat Developments Command Combat Service Support Group. Fort Lee. Virginia - Z301 Headquarters. U. S. Army Munitions Command. Marine Cot ps Representative. ATTN: AMSMU-LM. Dover. New Jersey -
07801 110
Hq, U. S. Air Force. (AFMSPA- 1ionucleonics). ATTN: Special Weapons Defense Officer). Washington. D. C. - Z0333
m
.1U
DISTRIBUTION LIST NO. 5 (Contd) III 112
U.S. Marine Corps, ATTN: Staff Medical Officer (Code AM). Washing'on, D. C. - ZG60 Institute for Cooperative Research. University of Pennsylvanii. ATTN: Security Officer. TO: Librarian. Project Summit. 3634 Walnut Street, Ph iladelphia. Pennsy.ani- - 19104
113
Office. Chief of Research and Development, Department oi ane Army. Room 3E 440. ATTN: Chemical-Biologic,! Office. Washington 25, D. C. - 20301
114
Office of the Chief of Engineers. Department of the Army. ENGMC-ED. ATTN: Mr. James V. Malcolm. Washington.D.C. 20315 Officer in Charge. NBC Defense Do-partment. U. S. Naval Schools
115 116 o 117 l18 119 120 121 122 123 14 125
-
126
127
-
130
131
Headquarters.
150
Command. Treasure Island. San Francisco 30. California PHS Liaison Officer. Fort Detrick. Frederick. Maryland -217p". President. U. S. Army Airborne. Electronics & Special Warfare Board. Fort Bragg. North Carolina - 28307 President. U. S. Army Arctic Test Board. APO 733, Seattle. Washington Research Analysis Corporation. ATTN: Library. McLean. Virginia - 22101 Stanford Research Institute. ATTN: External Reports. G-037 (for Dr. Wilbur Benson). Menlo Park, California - 94025 Surgeon. U. S. A. Rocky Mountain Arsenal. Denver. Colorado 80240 The RAND Corporation. 1700 Main Street. ATTN: Library. banta Monica. California - 90406 U. S. Army Scientific Liaison and Advisory Group (9744). ATTN: Dr. Don L. Iseniterg. The Pentagon. Washington. D. C. -20310 U. S. Army Standardization Group. UK. ATTN: CBR Representative. Box 65. USN 100. FPO. New York. New York - 09599 USA CDC Liaison Officer. Hq. U. S. Army Munitions Command. Dover. New Jersey - 07801 Defense Documentation Center. Cameron Station. Alexandria. Virginia - 2.314
24
CONFIDENTIAL ABSTRACT
l
Orignating Activity
Za
Phvst oo1z Div:slcn U S Army Chemical Research and Development Laboratories Edgewood Arsenal. Maryland
Rep.rt Security C!assication SECRET
Zb
Gr-up tfor DDC use z-,
Report Title
SOME CHtEMICAL REACTIONS OF BZ tUl
Descriptive Note%
The -work was started in March 1961 and c.mpleted :n Aprat 196Z
Au'thors
Ilackley BrennJ E 11ackley, Ethel B
t
Publication Date
May 1964
8
Oricinator i Remnrt No
I
.
Jr
Cochrane. Chappelle C.
7
Tetal No. of Pages
I?
task
Z4
4C08-03 016 14
CRDLR 31I
10. Other Report
IZ.
Nus.
II
Supplementary Notes (f DDC use only)
Release S.atements ifor DDC use ,nt.yl
!!' "PI I' " N ME I'll'lC M M
13.
Author's Key Terms - Unclassified OnlI BZ Chemical reactions Detection Decontamination Biochemistry Metabolism Substituted compcundb Phenyl isocyanates Chemical agents Nitriles Incapacitating agents
Mechanism of action Amides Ritter reaction Alkyl halides Ammonium salts Quate rm zation Acetonitrile Spectrum Z. 4 -oxazolidinediones Biochemical action
14.
DDC Descrwtors (for DDC use only)
15
Identifiers - Unciassfieta Gu,
16.
Body of Abstract
(C) The purpose of this work was to conduct a fundamental study of the chemistry of BZ. to assist in problems that may arise in detection. decontamination, biochemical mechanism of action, and metabolism. BZ reacts with (0? substituted phenyl ssocyanates to yield. 2.4-oxazolidinediones. (2)nitriles to produce amrides (Ritter reaction). and (3) alkyl halides to give quaternary ammonium salts. Analysis of BZ can be accomplished by quaternization in acetonitrile. separation uf reactants, and assaying spectrally.
17.
Indexing Annotation Fundamental study of the chemistry of BZ to assist in the solution of problems of manufacture. storage. detection. decontamination, and bitchemical mechanism of -- tion.
--
L
CONFIDENTIAL ABSTRACT I - Originating Activity
Za.
Physiology Divisicn U. S. Army Chemical Research and Development Laboratories Edgewood Arsenal. Maryland
Reprt Security Classitication SECRET
Lb. Group licr DDC use onl#)
3. Report Title
SOME CHEMICAL REACT.'ONS OF BZ (U)
4.
Descriptive Notes
The vrqrk was started in March 1961 and c~mpleted in April 196Z.
5.
Authors
Hackley. Brennie E..* Jr. Hackley'. Ethel B.
6.
Publication Date
May 1964
8.
Orillinator's Report No.
Cechrane. Chappelle C.
7.
Tctal No. of Pages
9.
Task
4C08-03-016-14
CR:)LR IZ 13 10.
Other Report Nos.
12.
Release Statements (for DDC use cnly)
It.
Z4
Supplementary Notes (for DDC use only)
CONRiDEMUIL 13.
Authur's Key Terms
-
Unclassifited Only
BZ Chemiical rcai~ttonta Detection Decontamiunation biochemnistry Met aboli sm Substitutvd tottipoundo Phe.nyl i~ocyana-teb Chemical agents Nitriles IItapai. Itatti .-z-:nts
14.
DD
161
Identitiers
16.
Body of Abst. act
ecitr
tier OD
-
Mcchanism of ac~tion Aimades Rittei reactic Alkyl halidt.s Amimonium salts Quaterni Eat ion As. vionit rtiv Spectrum 2. 4-oxamolidinediones Bic hemaical action
us6, only)
Unclassified Only
(C) The purpose oi thi.%%ork %%as to conduct a fundamental atudy of the chemistry of BZ. to as-sist in problems that niay arise in detection. decontatminat ion.* biochemical mec hanism of action, and metabolismn. BZ reacts with Ml substituted phenyl isocyanates to yield. L. 4-c -tolldinedione s. (2) nitrilca to produce ainides (Ritter reaction). ,and (M alkyl hatlides to give quaternary ammonium salts Analysis of BZ can be accomplished by quaternization in acetonitrile. separation of reactants, and assavingt spe~ctrally
17
lrndextni Annotation Fun~damental study o! the chemistry of BZ to assist in the solution of problems of manufacture, storage. detect~on. decontamination. and biochemical mechanism of ition
CONFDENTIAL
ABSTRACT
1.
Originating Activuty
za.
Pvso!ogy DavISzn U. S. Army Chemical Pkcearch and Development Labor~t- ries Edgewood Arsenal, Maryland
3.
Report Title
4.
Descriptive Notes
Relprt Security Clasijification SECRET
Zb. Gr :2z .
f
