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REVIEW ON 28 MAY 84

SECRETCq U. S. Army

Chemical Research and Development LaboratoriesTechnical Report

cmnS Sr

_ by

Brennie E. Hackley, Jr.Chappelle C. Cochrane

Ethel B. Hackley C1il

LnJ

CD May 1964 D F ,

CRDL.6.OC-7DDCK\l-: D

EDGEWOOD ARSENAL, MD

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Not Autonatically Declassified. *13 ,

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l~r!!

May 1964 CRDLX 3213

SOME CHEMICAL REA.CTIONS OF BZ (U)

by

Brenwia Z. Hackley. Jr.Ckhsppet-le C. Cochran~e

-%'hel S Hackley

ftecc~ri eidirig Approv.ak

Colonel, MCDvrector of Methmal Regearch

Approved:

S. D. ShI.VZTec~ncal~ Direttor

U. S. Army £dSevmod ArsenalCHEMICAL aR=AftCH AND DEVZLOPMiE4T LABOkATORILS

Vdgewood ArsenAl. Marylanid

AMET

U14CLAID

(U) FOREWORD

This work wat conducted under Tatk 4Z08.03-016-;4. Bio-

chemical Action of Chemical Agents JU). The experimental data are contained

in notebooks MN-145Z, M24-1465. MN-1440, MN-1400.and MN-IS87. TI.

work was started in March 1961 &Mad completed ir. April 1962.

Ackncvledgtments

The authors wish to ackntmledg. the technical assistance ufMessrs. David E. Ronard. CI~ford ShIblom, 1Renneth E. Stine. and

Robert L. Green.

Notic eo

This dociment contains informatton affecting the rAtional defeneeof 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 authoriedto reproduce the dcunent for U. S. Go'ernment1 p,,rp'.ses

Disposition

When this document has served its purpose. DESTOY tt i,

acccrdance with AR 380-5 DO NOT retturn the documet to U. S. Arr y

Chemical Research and Development Laborttoriev.

UNCL_5-1|

| .. |

CONFIDENTIAL

(C) DIGEST

A fundamntal study of the cheminstry of 13Z wra condt-~te'd toassist in prob'sens tih&t may zrite in detecuon. dtvontasmialion. biochgtir-

mechanism of 3etion. and metaboism. BZ reicts *-2t~n (a) *ubstituspd pbenYI%&ocyanates Wo ysild 2. 4-oaaolinedionet. (b) nitriles to produ~ce a-rIded

(Ritter reaction). "it (c) alkyl )halades to give "~teronary amonist Wsat

Analysis of LIZ can he accompUshed by quattrnizatiotm iu acetonitrileseparation of reactan~ts. and &*saying asectral~

CONFIDENTL

3

SECRIET

IS) SOME CHEMICAL REACTIONS5 OF BZ (U)

(S) INTRODUCTION

(U) 8. is a crimpound that has be*-n ty~pe ctassified as an irm.apacitatingchernical agent To assist in the evaluation ot the biological properties of theagent- -adprobtemns of m.-nufacture, storage stability, detection, de.. -iftani-n~ation, bioch-emin~ mechantisni of action, and metabahtsr. a fundam,* tatotzdv of the chemist"i of 13Z has been m~ade.

IS) In thi- chemicAl structure of BZ there arre three primarf 7eactiv'esnes: Ia) the tetazv 0io.l() the estzr linkage, and (c) the quinuclidinyt

0P

nitrogen atom. A surv-:y of the literature (open anid classified) on benilateesters '.orainlrag a tertiary nitrogen .t !hew A-pos.-Oon of the alcoholmoietyl. 2, 3.4 shows that most attention has been directed to reactions 1! thetertiary nitrogen, i. e.. quaterruzztioln and salt formation, while little has beendone art the direct reactions of the hydroxyl function A considerable efforthas 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 hydroxylgroup as *ell as reactions vpecific for benzilate esters that invi 'e a bifunctional 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 assistin the analysis anid tdentaication of BZ and its metabolic products

11 (S) PROCEDUPLr AND RESULTS.

A, (S) Z, 4- Oxsolildirtediones.

(5) One of the clsasic modes of formation of 2.4-oxazolidinedionesresults from the teact;an of an .- hydr-5xyesterand an isocyanate to foem the

SECRET

corresponding urethane, which is subsequently cyclized by heat or alkalinecatalysta to the requsatte oxazolidinedione. 5

0 0 01I R"NCO _i

RCH-C-OR' - R-CH-C-OR---30R-CH _,4

I I IOH 0 NH-R" 0 3- '

C CsII 40 0

(S) In the special c~ase of benzilate esters, the oxazolhdinedioties areformed spnntaneously, even at low temperatureson reaction with an ire-cvanate. 6 This type of two-centered attack would b- specific for benzilateesters such as BZ. By judicious selection of the isocyanate. the N-subtt-tuted-5o 5-diphenyl oxazolidinedione (obtaintd as a single product) coul"possibly be analyzed by iluorescent, colorimetric. infrared, or other physical

\c-L-o~QRNCC/ C __ 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 ofOxasolidinedionet 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

2 (U) Results.

The oxazoldinediones prepared are listed si table I They all

exhbxit character,.a.,i infrared absorption% in the regions of 5. Sp (urethane)

and 5. 7p (amide).

D (S) Ritter Reaction Products

(S) Ritter et al7 reported the reaction of nitrtleb with alk,.nes or

tertiary akohoI4 to form 14 t-alkyl amides The presenct of - tertiary

alcohol group in BZ suggested the possible application of this reaction to BZ.

I (U) General Procedure lor the Ritter Rection.

A solution of I 3m (0. 003 mo!e) of BZ and 0.004 mote of nitrle

in 10 ml of glactal acetic acid was chilled in an ice bath and I5 w.1 of con-

centrated sulfuric acid added dropwise at a rate such that the temiw.awre

%was maintained between 5 to FO C. The reaction mixtre was stirred cold

for I hr and at room temuperature for Z hr The solution was poured onto

crushed ice and neutralized with saturated potassium carbonate soluiton. t1en

extracted with rbloroform, The extract was dried over anhydrous potasatun

carbonate or sodium sulate and the solvent removed. The residue was

c rystalliced from benzene or benzene patroleum ether (bp 30 ° to 6O0 C to

yield the desired produc,

Z () Results

Table 2 lists the Ritter products prepared They are colorless,

crysaailine solids with definite melting points and show no unusual character-

istit absorptions upon infrared analysis

0 0

R _ R- N K D if -I -

0

70

Sam

o 4 O4C 4 '0I i i _

_ _

_W_

~.. 0 ~ ~ C m

an -i A 4 -

0 2 IAft~

- j

0z zo ~ A -

= .

0- 9 -

w.

OWf .0?-L

0_

_

_

_

_

_

0~

S.

- fm N -

A

0A

SECRET

Z (U) Results

The oxazobdirediones prepared are listed in table I They allexhibit .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 ortertiary alcohols to form N -alkyl amides The presence rf % tertiaryalcohol 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 nitrilein 10 iml of glacial acetic acid was chilled in an ice bath and I ml of con-centrated sulfuric acid added drowise at a rate such that the tewas maintained between 5 to 10 C The reaction mixture wa, stirred coldfor I hr and at room temperature for 2 hr The soluti-n was poured ontocrushed ice and neutralized with satura,.ed potassium carbonate solution, thenektracted with chloroform. The extract was dried over anhydrous potassiumcarbonate or sodium sulfate and the solvent removed The resiaue wascrystallized from benzene or bcnzen,. petroleum ether (bp 300 to 60 0 C) toyield 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 charucter-istic absorptions upon infrared analysis

- 0 o,0KIII)\0

C-C-Q -4C-C--1

0\/l'r 1 111" 1 ! 11 1 '

0

SERE

UNLAMMD

I-

o *

0 r- 0 .0 I

*0 C

I u.*

04U -Vfq 0

0=

0 0m

s-s Q

O=U :c__ =U =U 0--u I I

ON ON efI

u

UNA*IFEI.9

SECRET

C. I", Quaternary Ammonium Compou.s.

(C) Wh-n a tertiary base is quaternized with an alkylhalhde. thedifferences in solubility of the salt-like product and the startnX materialsshould be sufficient to &llow spectral determination of the base. Severalsubstituted phenacyi bromide quaternaries of BZ were prepared

I (C) General Procedure for Prepration of QuaternarSalts.

A mixture of I gm (0.003 mole) of BZ, 0. 004 mole of the phenacylbromide. and ?5 ml of chloroform was allowed to stand at room temperaturefor IS hr. The solvent was removed under vacuum and the residue wascrystallized from ethanol-ether. acetonitrile-ether, or ethanol- 1, 2 dimethoxy-ethane.

Z. ts) Results.

These products, typical high-melting crystalline solids. arelisted in table 3

o0a 0 R-*-C-CHAX,.

OH1 X OHO0-. -c/RC -. C,,c o x

D. (C) bZ Acetate.

As part of this overall program, the authors were interested inpreparing the ac.lated der:vatives of BZ. In this connection attempts weremade to acetylate BZ with acetic anhydride and wth acetyl chloride ia pyri-dine to no avail. The infrared spectrum of BZ indicates strong intramolec-ula.. vr intermolecular hydrogen bonding, which is absent in its %salts. Thetionreactivity observed with the usual acetylating reagents may be due to thisbonding as well as to steric factors. Thus, treatment of the p-toluentsul-fonic acid *Idt of BZ with 3sopropenyl acetate afforded the acetate quitesmoothly.

SECRET10

COMFIENTIAL

(C) TABLE I

PHENACYL BROMIDE QUATIRIHARY SALTS OF BZ (C)

I Carbon flyd en

Alkyl halide Melting eld "point CalculatedFoud Cac;ua.,ed F-und

p-Phenylphercyl broaride 214-ZIS 9Z 68 68 168 9 5. S.7p-Nstrophencvl brow de 190-191 99 S9.9 158. 3 5 1 5 3

p. Brcmnophenacl br.mde 170-175 90 56.6 S6 61 4.8 4 8

is Naphthacv1 bromide ( Z0-2?4 931 7.7 16i 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 ofp-toluenesulfonic acid was reiluxed; acetone was distilled off slowly over aperiod of 5 hr. The riature was homogeneous at this time. The excessasopromenyl acetate woas removed under vacuum and the residue made alkalinewith coid saturated potassium carbonate solution. This was extracted with

chloroform, dried over anhydrous sodi.:n sulfate. and the solvent removedf-ider reduced pressur, The residue was refluxed with diethyl ether. filtered.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 bFound. 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 acetonitrileforming a quaternary salt. Since quaternarv salts have re)Atvely high solu-bsity inwater.one may separate the product from reactants and thus determinethe amount of tertiary amsne originaliy present. A plot of absorbancy versusconcentrat:on foilows Beer's law. Detailed procedures for the determinationof BZ in (a) acetonitr le. (b) water. and (c) in human whol* blocd follow.

CONFDETIALIi

CON4.0FIDENUiAL

Reaents: Recrystallized p-br.ziophenacyl bromide. spectrc-grade acc-.*i'e. , CP. 0 I N ris(hydroxy,-thyl)aminomethanc

(tris) buffer (p11 S. 5). cyclohexane. and BZ.

I (C) Determinauon of BZ in Actetonitrile.

(C) To 0. 1 ml of 10-? M solution of p-bromophenacyl 1,romidc inacetonitrile in a glass-stoppered bottle is added I to -10 ug of LZ dissolve,

in I ml of acetonitrile. The solution is mixed and heated in a 5(0C w:..r

bath tor 10 min After cooling the solution to room temperature Z ml of

0. 1 St KCI and 5 ml of cyclohexane are added and the mixture is mechanicallyshaken for 5 min. A portion of the aqueout phase is read spectrophoto-

metrically 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

BZ Absoroancy*'~~~~~g mlI Jll• I l

0 O.066.b O.Z05

5.Z . Z87. F. 0.456

10.4 0.59713.0 j 0.738

Average of five determinatiuns

Z. (C) Determination of BZ in Aqueous Solutions.

(C) To 2-ml aqueous solutions of BZ (5 to 40 ug) are added 0. Z mlof tris buffer (pH 8.5) and 3 ml of chloroform. The mixture ts shakenmechanically 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 NIAL

,.:__.,!, !!! '' l' "1

1.01

I

0.,

0.4

0. t

*0.1

.1

0.13

CONFIDENTIAL

(U) TABLE 5

DETERMINATION OF BZ IN AQUEOUS SOLUTIONS

BZ Absorbancyz

ugiml

0. 6Z 0 018T mi 1.2 5 0s 058

0--O. 5 0. 0lom s0 0 53

i 7.5 O0 39110.0 O, 517Iz 5 0 ,6'4o

sh t Average of five determinations e n0

3. (C) Determi~natio~n of 3Z in Huantan Whole Blood.

I(c i To I ml of human whole blood is added a 1-ml aqueous solution of

~BZ. The mixture is diluted to 7 ml and th-oroughly mixed. Onj millilitur of50% ZnSO 4 is added. mixed. and followtd by I -nt of 0. 3 N Ba(OH)Z . Chloro-

~form (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 theanalysis performed in acetonitrile as above (tabie 6. fi-are 31.

(U) TABLE 6

DETERMINATION OF BZ IN WHOLE BLOOD

BZ Absorb ancy'uglml

1 7 0 0623.4 0 1485,1 0 Z305.9 0.Z80

6.8 0.317

8 5 0.38810.2 1 0.478

* Average of four determirstions.

CONFIlENTAL!! [ 14

UNCLASSWD

09

0.S

0.7

0 o4

0.

1

0 ~~ !I 4 21 14 16

MI~t~gw . pew i1. zr. ouis

AtN&LTS1S Of 8Z V4 AQUW:US SOLUTIONS

is

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 toassist 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, tepara-

tion of reactanto, and assaying spectrally.

CONFIDENTIAL

UNCLASSIFIED(U) LITERATURE CITED

I. Ford-Moore, A. H., and Ing. H. R. Synthetic Mydriatics.J. Che.-- Soc. (London) 55 (1947).

Z. Sternbach. L. H.. ar4 haiser. S. Antispasmodics IIIEsters v, Bicyclic Alcohols ad Their Quiternary Salts. J. Am. Ch- .. Soc75. 6068 (1953).

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 SpectrophotometricEstimation of EA 2277 and Similar Compounds. Some Chemistry on theDecomposition of EA Z277 (U) June 1960 SECRET Me-rv.'-1ui

4 U. S. Army Chemical Research and DevilopmertLaboratories. CRDL Special Publication 4-28 EA Z277 (U). A 5-,'."'n ryReport as of 15 March 1961 March 1961 SECRET Report.

5 Clark-Lewis. 1. W, 2.4 Oxazolidinedione Chem Revs58. 63 (1955)

6 Rekker. R. F.. Faber. A. C.. Tom. D. H. E.,Verleur. H.. and Nauta. W T%. Rec. zrav chim 70. 1ld (1951).

7, Ritter. I.. and Kalish. I J. Am Cheax Soc 70,4048 (1948).

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98-103 Dr D. F. Downing. Defense Rearth Staff. Munitions/TW.British Embassy. 1100 Massachusetts Avenue. N. W. WashingtonS. D C.

104 Executive Director. EA CBR Advirory Council. Room Z7Z.Building 5101, Edgctood Arsenal, Maryland - 21010

105 Headquarters. AFLC (MCD). Wright-Patterson AFB. Ohio-45433

106 Headquarters. AFMTC. Deputy for Bioastronautics (MTX).ATTN: Col. William H Lee. USAF. MSC. Patrick Air ForceBase. Florida - 3±925

107 Headquarlers. AFSC (SCGB). ATTK. B. E. Flaherty. LI. Col..USAF. MC. Andrews Air Force Base, Washington, D. C. -Z0331

108 Headquarters. U. S. Army Cmbai Developments CommandComnbt Service Support Group. Fort Lee. Virginia - Z3gAI

109 Headquarters. U. S. Army Munitions Command. Marine CorpsRepre~er.tative. ATTN: AMSMU-LM. Dover, New Jersey -

07801110 Hq. U. S. Air Force. (AFMSPA-Bionucleonics). ATTN: Special

Weapons Defense Officer). Washington, D. C. - Z0333

I I lil e ~~UNLllAFlM !r ' r!,1

DISTRIBUTION LIST NO 5 (Contd)

89 Director, Biological Sciences Division (Code 440). Office of NavalResearch. Department of the Navy. 17th & C3nstitution Avenue.N. W.. Washingtor. Z5. D. C.

90 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

V 1-19Z Director of Engineering & Industrial Services, ATTN: PublicationsClerk. U. S. Army Edgewood Arsenal. Edgewood Arsenal.Maryland - 1010

93 Director. U. S. Army Edge.ood Arsenal. Operations ResearchGroup. Edgewood Arsenal. Maryland- Z1010

94 Director. U. S. Naval Research Laboratory. ATTN: Army LiaisonOfficer. Code 1071. Washington. D C. Z0390

95 Director. Walter Reed Army Inststute of Research. Dit-:in ofNeuropsychiatry. Washington. D. C. - 1001Z

96 Director. Wtlter Reed Army Institute of Research. Walter Reed

Army Medical Center. Washington. D. C. - Z002Z97 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.98-103 Dr D. F. Downing. Defense Reseat ch Staff. Munitions/TW.

British Embassy. 3100 Massachusetts Aicnue. N. W. Washington8. D C.

104 Executive Director. LA CBR Advisory Council. Room Z7Z,Building 5101. Edgewood Arsenal. Maryland - ZI010

105 Headquarters. AFLC (4?CD). Wright-Patterson AFB. Ohio-45433

106 Headquarters. AFMTC. Deptity for Bioastronautics (MTX).ATTN: Col. William H Lee. USAF, MSC. Patrick Air ForceBase, Florida - 3Z9Z5

107 Headquarters, AFSC (SCGB). ATTN. B. E. Flaherty. Lt. Col.,1.SAF. MC. Andrews Air Force Base, Washington, D. C. -Z0331

106 Headquarters, U. S Army Combat Developments CommandCombat Service Support Group. Fort Lee. Virginia - Z301

109 Headquarters. U. S. Army Munitions Command. Marine Cot psRepresentative. ATTN: AMSMU-LM. Dover. New Jersey -

07801110 Hq, U. S. Air Force. (AFMSPA- 1ionucleonics). ATTN: Special

Weapons Defense Officer). Washington. D. C. - Z0333

m .1U

DISTRIBUTION LIST NO. 5 (Contd)

III Headquarters. U.S. Marine Corps, ATTN: Staff Medical Officer

(Code AM). Washing'on, D. C. - ZG60112 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 aneArmy. 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.

20315115 Officer in Charge. NBC Defense Do-partment. U. S. Naval Schools

Command. Treasure Island. San Francisco 30. California116 o 117 PHS Liaison Officer. Fort Detrick. Frederick. Maryland -217p".

l18 President. U. S. Army Airborne. Electronics & Special Warfare

Board. Fort Bragg. North Carolina - 28307119 President. U. S. Army Arctic Test Board. APO 733, Seattle.

Washington

120 Research Analysis Corporation. ATTN: Library. McLean.

Virginia - 22101121 Stanford Research Institute. ATTN: External Reports. G-037

(for Dr. Wilbur Benson). Menlo Park, California - 94025122 Surgeon. U. S. A. Rocky Mountain Arsenal. Denver. Colorado -

80240

123 The RAND Corporation. 1700 Main Street. ATTN: Library. banta

Monica. California - 90406

14 U. S. Army Scientific Liaison and Advisory Group (9744). ATTN:Dr. Don L. Iseniterg. The Pentagon. Washington. D. C. -20310

125 - 126 U. S. Army Standardization Group. UK. ATTN: CBR Representative.Box 65. USN 100. FPO. New York. New York - 09599

127 - 130 USA CDC Liaison Officer. Hq. U. S. Army Munitions Command.

Dover. New Jersey - 07801

131 150 Defense Documentation Center. Cameron Station. Alexandria.

Virginia - 2.314

24

CONFIDENTIAL

ABSTRACT

l Orignating Activity Za Rep.rt Security C!assication

Phvst oo1z Div:slcn SECRETU S Army Chemical Researchand Development Laboratories Zb Gr-up tfor DDC use z-,

Edgewood Arsenal. Maryland

Report Title SOME CHtEMICAL REACTIONS OF BZ tUl

I Descriptive Note% The -work was started in March 1961 andc.mpleted :n Aprat 196Z

. Au'thors Ilackley BrennJ E Jr Cochrane. Chappelle C.11ackley, Ethel B

t Publication Date May 1964 7 Tetal No. of Pages Z4

8 Oricinator i Remnrt No I? task 4C08-03 016 14

CRDLR 31I

10. Other Report Nus. I I Supplementary Notes(f DDC use only)

IZ. Release S.atements ifor DDC use ,nt.yl

!!' " PI I' " I 'll'lC N ME M M

13. Author's Key Terms - Unclassified OnlI

BZ Mechanism of actionChemical reactions AmidesDetection Ritter reactionDecontamination Alkyl halidesBiochemistry Ammonium saltsMetabolism Quate rm zation

Substituted compcundb AcetonitrilePhenyl isocyanates SpectrumChemical agents Z. 4 -oxazolidinedionesNitriles Biochemical action

Incapacitating agents

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 thechemistry 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 BZcan be accomplished by quaternization in acetonitrile. separation ufreactants, and assaying spectrally.

17. Indexing Annotation

Fundamental study of the chemistry of BZ to assist in the solutionof problems of manufacture. storage. detection. decontamination, andbitchemical mechanism of -- tion.

-- L

CONFIDENTIAL

ABSTRACT

I - Originating Activity Za. Reprt Security Classitication

Physiology Divisicn SECRETU. S. Army Chemical Research

and Development Laboratories Lb. Group licr DDC use onl#)Edgewood Arsenal. Maryland

3. Report Title SOME CHEMICAL REACT.'ONS OF BZ (U)

4. Descriptive Notes The vrqrk was started in March 1961 andc~mpleted in April 196Z.

5. Authors Hackley. Brennie E..* Jr. Cechrane. Chappelle C.Hackley'. Ethel B.

6. Publication Date May 1964 7. Tctal No. of Pages Z4

8. Orillinator's Report No. 9. Task 4C08-03-016-14

CR:)LR IZ 13

10. Other Report Nos. It. Supplementary Notes(for DDC use only)

12. Release Statements (for DDC use cnly)

CONRiDEMUIL

13. Authur's Key Terms - Unclassifited Only

BZ Mcchanism of ac~tionChemiical rcai~ttonta AimadesDetection Rittei reacticDecontamiunation Alkyl halidt.sbiochemnistry Amimonium saltsMet aboli sm Quaterni Eat ionSubstitutvd tottipoundo As. vionit rtivPhe.nyl i~ocyana-teb SpectrumChemical agents 2. 4-oxamolidinedionesNitriles Bic hemaical actionIItapai. Itatti .-z-:nts

14. DD ecitr tier OD us6, only)

161 Identitiers - Unclassified Only

16. Body of Abst. act

(C) The purpose oi thi.% %ork %%as to conduct a fundamental atudy of thechemistry 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 BZcan be accomplished by quaternization in acetonitrile. separation ofreactants, and assavingt spe~ctrally

1 7 lrndextni Annotation

Fun~damental study o! the chemistry of BZ to assist in the solutionof problems of manufacture, storage. detect~on. decontamination. andbiochemical mechanism of ition

CONFDENTIAL

ABSTRACT

1. Originating Activuty za. Relprt Security Clasijification

Pvso!ogy DavISzn SECRETU. S. Army Chemical Pkcearch

and Development Labor~t- ries Zb. Gr :2z . f<r DDC u'tr cn.Edgewood Arsenal, Maryland

3. Report Title SOME CHEMCAL REACT:ONS OF BZ (U)

4. Descriptive Notes The w-rk w.- oarted in March 1961 andc-:mpleted in Apris 1962.

5. Authors Hackleyo Brennie E., Jr. Ccchra t. Chappelle C.Hackley, Ethel B.

6. Pubc.ation Date May 19'A 7. Total No. of Pages 24

8. Originator s Reprirt No. 9. Task 4CO8-03 -016-14

CRDLR 3213

10. Other ReErt Ncs. 1i. Supplementary Nites(frr DDC use cnlv)

It. Release Statementq fUrr DDC -,se on:vl

CONFIDENTIAL

C-ONFIDENTIA4L

11~. Autho' Key Terms -Unclasoalied Onli

83z Mechanism of action

Chemical reactions Amides

Detection Ritter reactionDe~c oftamtIIflt ion Alkyl halides

Biochemistry Ammonium salts

Metabolism QuaternizationSubstituted cvmpounds Acetonitrilk

Phenyl isocyanates Spectrum

ChemICAI agent s Z.4 .oxazolidincduones

Nstriles Biochemical action

Inc apai. atatt'r :ttntS

14. DDC Descriotors (for DDC, use only)

15 Identifiers -Unclasiified Only

lb. Body of Abstract

(C) The pirpose of this work was to conduct a fundamental study of the

chemistry of BZ, to assist in problems that may arise in detection.

d..centainination. bio~hemical mechanism of iton, and Meiabolism.

8Z reacts with WI substituted z; ~ -

2.4-oxazolidmnediones. Q)I nit riles to produce amides (Ritter reaction).

and (3) alkyl halides to pive quaternary .immonsum salts Analysis of BZ

can be a--omplished by quaternization in acetonitrile. separation of

reactants and assaving spect rally.

1 7 Indexing Annotation

Fundamnial study of the chemistry of BZ to assist in the solution

of problemns of manufacture. storage. detection. decontamination, and

biochemical mechanism of a-:ion

REPLY TO ATTENTION OF

AMSRD-ECB-TD

DEPARTMENT OF THE ARMY US ARi\ilY RESEARCH, DEVELOPi\ilENT AND ENGINEERING COMMAND

EDGEWOOD CHEMICAL BIOLOGICAL CENTER 5183 BLACKHAWK ROAD

ABERDEEN PROVING GROUND, MD 21010-5424

2 7 ��M 2009

MEMORANDUM FOR Army Declassification Activity, 8850 Richmond Highway, Suite 300, IMP Building, Alexandria, VA 22309

SUBJECT: Declassification Review

1. References:

a. Executive Order 12958, Classified National Security Information, dated 17 April 1995.

b. Executive Order 13292, Classified National Security Information, dated 25 March 2003.

c. AR 380-5, DA Information Security Program, dated 31 October 2000.

2. In accordance with the references listed above, the purpose of tllis memorandum is to provide the recommendation made by the Edgewood Chemical Biological Center (ECBC) Security Classification Review Board (SCRB), regarding declassification and downgrading of the below listed documents.

a. Isokinetic Sampling of H Aerosol, (ADA Case 080 19), (as Produced by the Comings Candle), February 1946. Downgrade from Confidential to Unclassified/Unlimited.

b. Dugway Proving Ground Research and Development Weekly Report (Part A), Medical Research Laboratory Weekly Repmi (Pmi B), Dugway Proving Ground Mobile CWS Unit Weekly Report (Part C), (ADA Case 08024), February 1945. Distribution authorized to U.S. Govermnent agencies and their contractors. Downgrade from SECRET to Unclassified/Wnlimited.

c. Dugway Proving Ground Research and Development Weekly Report (Part A), Medical Research Laboratory Weekly Report (Part B), Dugway Proving Ground Mobile CWS Unit Weekly Report (Part C), (ADA Case 08023), January 1945. Downgrade from SECRET to Unclassified/Unlimited.

d. Counter-Insurgency and Air Power: Report of a Rand Ad Hoc Group, (ADA Case 07078), June 1962. Downgrade from SECRET to Unclassified/Unlimited.

e. The Role of Chemical and Biological Weapons in the Defense Strategy of the United States, (ADA Case 08002), December 1964. Retain at Confidential. c 1 _ l--1 _ 2 S .3 'j

0 7 _ m� 2 tl-51 o 7- m- 28 31,

. � o7 .... m. 2£?31..{ +hro�Lc,h 07-m- 2.:?38 Pnnled on \;t1 Re,:ycled Paper

.

V

07-m- �8-'-/2._

AMSRD-ECB-TD SUBJECT: Declassification Review

f. Special Report: The Increment Flow Regulation Valve, (ADA Case 08020), 3 December 1945. Distribution authorized to US Government agencies only.

g. Interim Report: Development of Decontamination Solution Unit, 3-Gallon, E8R2, (ADA Case 08003), 15 February 1954. Retain at Confidential. o1- �'vt ..- 2. �) �

h. Chemistry of BZ.I. Reaction of BZ with Iodine in Aqueous and Organic Solution, (ADA Case 08007), November 1962. Downgrade from Confidential to US Government Agencies and their contractors. C'-;---- P!f- 2-g 7 7

i. Interim Report: Decontamination of Airplanes (F.Y. 53), (ADA Case 08006), 19 November 1953. Retain at Confidential.

· · ·

j. Chemical Defense Experimental Establislunent Portion, (ADA Case 0801 0), 4 December 1954. This document contains Foreign Govenunent Information (British) and the decision should be deferred to them.

k. An Evaluation of the Relative Efficacy of Five Self-Injection Ampoules, (ADA Case 08011), December 1952. This document contains Foreign Government Information (British) and the decision should be deferred to them.

I. Infrared Spectra and Absorption Coefficients for GA, GB, GD, VM, VX, and the G analog (Reaction Product ofVX and Conversion Filter), (ADA Case 08000), August 1966. Retain as US Government Agencies and their contractors. {) ·1·- )"'/- -z_ 0 '"2---· .:i�

111. Estimate of Minimal Effective Dose of BZ by the Intramuscular Route in Man, (ADA Case 08004), November 1965. Downgrade from Confidential to Unclassified, US Government agencies and their contractors. c.' • 7 - /Lf - '?- � 3 /

n. Stability Testing of M138 BZ Bombs, (ADA Case 08008), August 1966. Downgrade from Confidential to Unclassified, US Government agencies and their contractors. 0 1f- N ...- 2 f.· '3)

o. Some Chemical Reactions of BZ, (ADA Case 08009), May 1964. Downgrade from Confidential to Unclassified/Unlimited. o ? - J'/ - -:;.. 9- Y r£'

3. The point of contact is Mr. Jeremy Taylor at 410-436-6810 or jeremy. taylor2@us.Cirmy.mil.