Pl-zoreeeemsmv or
BfOACTNE COMPOUNDS _

I. SolutionePhase Photochemistry of
Asymmetrie Triazin-S-(4H)-‘0nes . ‘

H. Sqution-Phase Photoehemistry of , "
Symmetrical Triazines '

Thesis for the Degree of Ph. :D.
MICHEGAN STATE UNIVERSHY
BRIAN E. PAPE
197 2.5

This is to certify that the

thesis entitled
Photochemistry of Bioactive Compounds

I. Solution-Phase Photochemistry of
Asymmetric Triazin-S-(hH)-Ones
ll. Solution-Phase Photochemistry of Symmetrical Triazines
presented by

Brian E. Pape

has been accepted towards fulfillment
of the requirements for

Ph . D. degree in __E[11‘.Qm9_l_ng

 

Mew!

Major profit
Date??? /5/~/777

0-7 639

 

   
    
    

BINDING IV

LIBRARY BINDE RS
gal-em}. mama;

“”' ABSTRACT
PHOTOCHEMISTRY OF BIOACTIVE COMPOUNDS
I. Solution-Phase Photochemistry of Asymmetric Triazin—S-

(4H)-Ones.

II. Solution—Phase Photochemistry of Symmetrical Triazines
BY

Brian E. Pape

The photolysis of 4-amino-6-R-3-(methylthio)-a§f

triazin-S-(4H)-ones (R - cyclohexyl, Efbutyl, isopropyl) in
carbon tetrachloride, benzene, methanol, water, or in the
crystalline state, yields the respective S-hydroxy-6-R-3-
(methylthio)—l,2,4-triazine as the major product. Minor
reactions proceed by routes which include desulfurization
and oxidation. Reaction mechanisms are considered.
Photolysis of 2-fluoro and 2-bromo-4,6-bis(ethyl—
amino)—§ftriazine in methanol and water at 253.7 and 300 nm
yielded the 2-methoxy and 2-hydroxy analogs as the major
products. Photolysis of the 2-iodo-g—triazine analogs of
atrazine, propazine, and simazine in methanol, ethanol, and
nebutanol at 300-360 nm yielded the respective 2-alkoxy and

2—hydroxy compounds as the major product(s). Reaction

Brian E. Pape

mechanisms are Considered. Consideration of thermal,
photochemical, and spectroscopic data are suggestive of the
participation of a Chugaev-type cyclic transition state in
the photochemical dealkylation of s—triazines. Photolysis
of 2-azido-4-ethylamino-6-methylthio-sftriazine in methanol
at 253.7 and 300 nm yielded 2-amino-4-ethy1amino—6—methyl—
thio-s-triazine, 2-amino-4-ethylamino—sftriazine, and 2-
azido-4-ethylamino-s—triazine. The observation of a "sen-
sitized" photodecomposition of 4,6-bis(isopropylamino)-§-

triazine is reported.

II.

PHOTOCHEMISTRY OF BIOACTIVE COMPOUNDS
Solution-Phase Photochemistry of Asymmetric Triazin-S-
(4H)—Ones.

Solution-Phase Photochemistry of Symmetrical Triazines.

BY

Brian EfiPape

A THESIS

Submitted to
Michigan State University
in partial fulfillment of the requirements
for the degree of

DOCTOR OF PHILOSOPHY
Department of Entomology

197

ACKNOWLEDGMENTS

The generosities of my major professor, Dr. M. J.
Zabik, have added immeasurably to my personal and scien-
tific development during my graduate career. The encourage-
ment and support of my participation in the formulation and
public presentation of several research projects is greatly
appreciated. I deeply hope that others shall have these
same opportunities.

The patience and cooperation of my guidance commit-

tee members is noted with thanks.

ii

TABLE OF CONTENTS

Part I. Solution—Phase Photochemistry of
Asymmetric Triazin-S-(4H)-Ones

INTRODUCTION . . . . . . . . . . . . .
EXPERIMENTAL . . . . . . . . . . . . .
Material and Methods . . . . . . . . . .
Photochemical Procedures . . . . . . . .
RESULTS AND DISCUSSION . . . . . . . . . .
Elemental Analyses and Melting Points . . . .

Thin—Layer Chromatography and Gas —Liquid
Partition Chromatography . . . . . . . .

Mass Spectrometry . . . . . . . . . . .
Infrared Spectroscopy . . . . . . . . .
Nuclear Magnetic Resonance Spectra . . . . .
Reaction Mechanism . . . . . . . . . .

Minor Photoproducts . . . . . . . . . .
CONCLUSIONS . . . . . . . . . . . . .
LITERATURE CITED . . . . . . . . . . . .

Part II. Solution-Phase Photochemistry of
Symmetrical Triazines

INTRODUCTION 0 0 O O O O O O O O O O 0
EXPERIMENTAL MATERIALS AND METHODS . . . . . .
S—Triazines . . . . . . . . . . . . .
Solvents . . . . . . . . . . . . . .
Chromatography . . . . . . . . . . . .
Instrumentation . . . . . . . . . . .

iii

Page

\J

OKDCD@\!\]

19

21
26

26
26
26
27

RESULTS AND DISCUSSION

2-Azido—4-Isopropylamino-6-Methylthio-

S-Triazine

"Sansitized" Reactions
Z-Fluoro and 2-Bromo-S—Triazines
2-Iodo-S—Triazines

2—Chloro-S—Triazines
Photochemical Dealkylation

CONCLUSIONS .

LITERATURE CITED

iv

Page

28

28
30
30
30

37
39

41

43

Table

LIST OF TABLES

Part I. Solution-Phase Photochemistry of

Asymmetric Triazin-S-(4H)-Ones

Elemental analyses and melting points
of photoproducts . . . . . . .

Thin—layer chromatographic and gas-liquid
partition chromatographic data for
asymmetric triazin—S-(4H)-Ones and
photoproducts . . . . . . . .

Nuclear magnetic resonance (nmr) data of
asymmetrical triazin-S-(4H)—One
photOproducts . . . . . . . .

Part II. Solution-Phase Photochemistry of

Symmetrical Triazines

Authentic g-triazines and photoproducts

Page

14

LIST OF FIGURES
Figure Page
Part I. Solution-Phase Photochemistry of

Asymmetric Triazin-S-(4H)-Ones

1. Mass spectra of ag-triazin-S-(4H)-Ones
1—111 and respective photoproducts
IV-VI O I I O O O O O O O O O O 0 l 6

2. Infrared spectra of asftriazin-S-(4H)-Ones
I-III and respective photoproducts IV-VI . . 17

Part II. Solution-Phase Photochemistry of
Symmetrical Triazines

l. Graphical representation of mass spectrum of
2-n—decoxy-4,6-bis(isopropylamino)-§-
triazine (70eV) . . . . . . . . . . 38

vi

PART I. SOLUTION-PHASE PHOTOCHEMISTRY OF
ASYMMETRIC TRIAZIN-S-(4H) ONES

INTRODUCTION

A number of 4-amino-6-alky1 substituted-3-(methyl-
thio)-a§-triazin-5—(4H)—ones were previously tested for
herbicidal activity by Vero Beach Laboratories, Inc., and
are currently being developed by Chemagro Corp. (Kansas
City, Mo.) under license. Representatives of this class of
compounds included in this investigation of photochemical
reactivity include: BAY 94337 [4-amino-6—t—butyl-3-
(methylthio)—a§-triazin-5-(4H)-one] (I), BAY 88410 [4-amino-
6—isopropyl-3-(methylthio)-a§-triazin-5—(4H)-one] (II), and
BAY 86791 [4-amino-6-cyclohexyl-3—(methylthio)-a§ftriazin-

5-(4H)-one] (III). 0

R \N—NH2

(p...

Asymmetric heterocyclic nitrogen compounds have

 

 

been the subject of extensive investigation (Paquette,
1968; Smolin and Rapoport, 1959). Even a superficial

review of the literature indicated several plausible

reaction pathways that might be operative in the photo-
decomposition of I-III: expulsion of molecular nitrogen
with the formation of the intermediate biradical; desul-
furization of the carbon-three methylthio group; oxidation
of a hetero atom; reduction of or addition to the carbonyl
function; dimerization; and addition to the unsaturated
ring (Calvert and Pitts, 1966; Crosby, 1969; Mustafa, 1964;

Neckers, 1967; Pape and Zabik, 1970; Plimmer, et al., 1969).

EXPERIMENTAL

Materials and Methods

 

Herbicides

 

Compounds I—III were obtained from Chemagro as
technical material and were recrystallized from benzene to
greater than 99% purity. Alternatively, they may be
recrystallized from 1,2-dichloroethane. Final purification
may be accomplished by tlc using silica gel and benzene-
ethyl ether (1:1) or chloroform-acetone (9:1). Chemical

authenticity was supported by ir, mass, and nmr spectra.

Solvents
All solvents were of analytical grade. Water was
distilled, degassed, deionized, and had a pH of approxi-

mately 6.8.

Photochemical Equipment

 

All photolyses were done in a Rayonet Photochemical
Reactor (The Southern N. E. Ultraviolet Co.) fitted with
lamps having a peak energy output at 300 and 350 nm (Cata-
log No. N.P.R.-3000, -3500, respectively). All irradi—

ations were done through borosilicate glass. Solutions

were magnetically stirred, with solution temperatures

maintained at approximately 25° C.

Analytical Equipment

 

Thin-layer chromatography (tlc) was done on pre-
coated silica gel (HF-254) plates, with chloroform-acetone
(9:1) or benzene-ethyl ether (1:1). Column chromatography
was done on silicic acid AR 100 mesh (Mallinckrodt), using
chloroform-acetone (9:1). Gas—liquid partition chroma-
tography (glpc) analyses were accomplished using a 3% OV-l
or 1% SE-3O liquid phase on Gas-Chrom Q (Applied Science
Laboratories), with an isothermal temperature range of
l60-200° C.

All melting points were uncorrected. Infrared (ir)
and ultraviolet (uv) spectra were determined with a Perkin—
Elmer 337 and Beckman DB-G grating spectrophotometer,
respectively. Nuclear magnetic resonance (nmr) spectra
were recorded using a Varian A-60 high resolution instru-
ment. Samples were dissolved in deuterated chloroform-dl
or acetonitrile-d3, with tetramethylsilane as an internal
standard. Mass spectra were obtained with an LKB 9000 gas
chromatograph-mass spectrometer. Spectra obtained by
direct or indirect (1% SE-30 liquid phase on 60/80 mesh
Gas-Chrom Q; 6 ft. x l/8 in. i.d.; isothermal temperature
150-200° C.; ionization voltage 70 eV) introduction were

essentially identical.

Elemental analyses were performed by Spang

Microanalytical Laboratory, Ann Arbor, Mich.

Photochemical Procedures

 

Photolysis of 4-Amino-6-Alkyl Substituted-3-
Methylthio)—As-Triazin-5-(4H)-Ones (I, II,
III) in Carbon Tetrachloride, Benzene,
Methanol, and Water.

 

 

 

 

Photolysis of saturated solutions of I-III in car-
bon tetrachloride (0.25 g./100 ml. solvent) at > 290 nm
resulted in reaction, and precipitation of the respective
major photoproduct (IV-VI). With short irradiation time,
i.e., four hours or ~ 10% conversion of I-III, product
yield was greater than 90%. Prolonged photolysis (> 72
hours) resulted in multiple products (with total conversion
of I-III, yield of IV-VI exceeded 60%.

Reactions were stOpped with the total disappearance
of I-III; solvent was removed under partial vacuum; and the
amorphous residue was dissolved in chloroform-acetone
(9:1). This solution was chromatographed on a silicic acid
column [chloroform-acetone (9:1)]. Fractions were analyzed
by glpc and tlc; pure product fractions were reduced under
vacuum; and final drying was done in a drying pestle.

Comparative analysis of aliquots of starting mate—
rial, photolysis solutions, and isolated photOproducts by
glpc and tlc showed the product to be stable under these
chromatographic procedures. Solutions of I-III held in the

dark were determined to be stable over time.

Photolysis of I-III in Other Solvents

 

Photolysis of I-III in benzene, methanol, and water
yielded essentially identical results: conversion of I-III
to appropriate major product identical to that formed in
carbon tetrachloride. Photolysis in water required the

extraction of product with ethyl ether or chloroform.

Photolysis of I-III in the Crystalline State

 

Compounds I-III were dissolved in ethyl ether and
distributed over the inside surface of a borosilicate flask
(using rotation and air stream). Irradiation through glass
resulted in a photo-reaction, with formation of a major
product identical to those isolated from solution-phase

reactions.

RESULTS AND DISCUSSION

Elemental Analyses and Melting Points

 

Elemental analyses showed that the major photo-

products of I-III had lost the equivalent of NH (Table l).

Thin-Layer Chromatography and Gas-Liquid
Partition Chromatography

 

 

Tlc and glpc behavior of starting materials and
photolysis products (Table 2) suggested that the major iso—
lated products (IV-VI) were more polar than their respec-
tive precursors [refer to Pape and Zabik (1970) for behavior
correlations noted for series of carbon-two substituted

s-triazine analogs].

Massg§pectrometry

 

The mass spectra of these photoproducts are charac-
terized by a molecular ion 15 m/e units below their respec-
tive starting material: the even mass number and isotOpic
abundance supported the loss of NH. Although, in each
case, the base peak appeared at m/3 69 and suggested a com-
mon molecular genesis, the fragmentation pattern was insuf-
ficient to determine whether rearrangement of the hetero-

cyclic ring had occurred (Figure 1).

Infrared Spectroscopy

 

The ir spectra of I-III and their respective prod-
ucts exhibited striking dissimilarities: loss of primary
amine stretching vibrations in the 3300 cm—1 region;
increased absorption and complexity in the 1600-1700 cm-1
region of the ir--suggestive of an intramolecularly bonded
carbonyl or enol function; and appearance of an intense
absorption between 2500-3000 cm-l, strikingly similar to
the observed enol-keto tautomerism occurring in the ir
spectra of 2—hydroxy-s-triazines (Padgett and Hamner, 1958;
Pape and Zabik, 1970) (Figure 2).

These data suggested the 1,2,4-triazine ring system

(VII) as the photoproduct.

OH

Nuclear Magnetic Resonance Spectra

 

The nmr spectra of I-III and products (Table 3)
supported the proposed structural system by the absence of
a primary amine (2H) signal and the relatively unaltered
chemical shifts of the SCH3 and alkyl functions in product

spectra. The absence of a one hydrogen signal for the

enol-keto tautomer is attributed to exchange.

These data allowed the assignment of structures to
the respective photoproducts of I-III as 5-hydroxy-6-E—
buty1-3-(methylthio)-l,2,4-triazine (IV), 5-hydroxy-6-
isopropy1-3-(methylthio)-1,2,4-triazine (V), and 5-hydroxy-
6-cyclohexyl-3-(methylthio)-1,2,4-triazine (VI).

0 OH
'-NH hv
w, MFA
N
3 :7J‘“ SCH3

‘\\N’/ SCH N\wq

0 OH
_ \
I N NH2 hv 9 I N
/ SCH N J
\N 3 \N/ SCH3
0 OH
__ hV \\.
N j— N
\N/ SCH3 \N/LSCH3

Reaction Mechanism

 

One attractive reaction pathway for the conversion
of I-III + IV—VI involves an intramolecular hydrogen
abstraction, mechanistically analogous to the gamma-hydrogen
abstraction of aliphatic ketones (Calvert and Pitts, 1966).
This would involve excitation of the carbonyl, gig some

unelucidated excited state, to yield a "biradical." This

min-q

10

radical would then abstract an amine hydrogen via an intra—
molecular five-membered cyclic transition state, followed

by electron shift, with elimination of NH to yield product.

H ' H
O \NH O \
R NH
/ R o /

I N HV

   
 

 

3 3
,"H
OH O, \\
' NH
NH
R Z R . ///
N \
N
N%%i\scn \\N%%i\
3 OH SCH3
R

L r:

”\N

SCH3

 

Minor Photoproducts

 

Chromatographic and mass Spectral data suggest that
the minor photOproducts formed after prolonged irradiation
of I-III or IV-VI in solution or as a solid consist of com-
pounds whose formation is explicable in terms of hetero
atom oxidations, intramolecular rearrangements, and desul-

furization. Although not definitely identified, reaction

ll

mechanisms leading to such product multiplicity are based

on reported literature and structural/photochemical analo-

gies.
0 OH
R ‘ — NH2 R \
N A A
\N o \N o
H H
OH O
\\
R R N—NH
' 2
/’ ‘//l\
\\N H \\N’/’ H
o o
R | KN R N—N=N—
N /|L N ,I’ x
\N OH \’ ‘

Formation of the "dicarbonyl" analogs of I-III may
proceed gig a sulfone or sulfoxide intermediate formed by
photo-oxidation of the methylthio group [Plimmer, ei_gi,,
1969, postulated that the unstable sulfone or sulfoxides
of 2-methylthio-sftriazines would yield their 2-hydroxy

analogs]. The cyclic hydroxylated ketones might then be

12

formed by the competitive elimination of NH from the "dicar-
bonyl," analogous to I—III + IV-VI. Hydroxy or keto desul-
furization products may be formed gig an elimination mech-
anism similar to that reported for gftriazines (Plimmer,
ei_gi., 1969; Pape and Zabik, 1970. Other pathways may
include dimerization yia_amine hydrogen abstraction to

yield azo compounds (Rosen, §i_3i,, 1970) and head-head or
head-tail dimerization products (Neckers, 1967). At pres-
ent, there is no analytical evidence to support the occur-

rence of these latter products.

l3

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o
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mma ma.va Hm. . . . . . . m ma oa
m va om ma mm ma mm 0 mm m om mm em mm AH>vmo z m U
m . . . . . . . . m Ha m
n «a em ma om ma om mm mm mm mm m 00 0 mm me mm me A>vmo z m U
«sad oa.oa Ho.ma oo.am Ho.am hm.o mm.m ma.ms Hm.ms A>vaomzmammo
Umcfifiuouoa pcsom poamo pcsom poamu chom UUHMO pcsom poamo mammamcd
Oo unmasm comouufiz cmmoupmm conumu uosooumouocm

 

.mDUSUOHQODOQQ mo mucflom mcHuHoE mam mommamsm HmucmEon|l.H mamda

14

TABLE 2.--Thin-1ayer chromatographic and gas-liquid par-
tition chromatographic data for asymmetric tria-
zin—5-(4H)—ones and photoproducts.

 

 

 

 

TLC Data GLPC Data
Compound Solvent Relative Rf Columnb Retention
Systema (1 = 1.00) Time, Min
I A 1.00 A
B 1.00 B .
II A .81 A
B .76 B
III A .92 A 11.8
B .87 B --
IV A .66 A
B .54 B .
V A .56 A
B .35 B
VI A .71 A --
B .41 B --
aSolvent system: (A) = chloroform/acetone (9:1
v/v). (B) = benzene/ethyl ether (1:1 v/v).

bColumn: (A) = 3% OV—l liquid phase on 80/100 Mesh
gas-Chrom Q; 6 ft. stainless steel column - 1/8 in. i.d.;
carrier gas flow 25 ml/min helium; flame ionization
detection.

(B) = 1% SE-30 liquid phase on 60/80 mesh Gas-Chrom
Q; 6 ft. borosilicate glass column-l/8 in. i.d.; carrier
gas flow 40 ml/min helium; electron ionization detection.

5
l

 

 

umamfluasfi u AEV .umansoo u Apv .umamcfim u Amy
.mEu ou o>HumHou .mmsHm> APV smu CH Ummmmumxm mamanm HMUHEmco uEzm
AEVImHHVImm.mV Amylmmvos.h zomao H>
AEVImHVmH.~ AeVImkaH.m Imelmmvom.n zomau >
Imelmmco.m Imelmmcmk.h zomou >H
Aalimaavom.m Amvflmmvmm.s ImVAmmvmm.n maoao HHH
Agelmflvmm.w 1831mmvom.m AmVAmmvmm.s Amelmmvmm.n maooo HH
Amelmmvoe.m AmVAmmvmm.s AmVAmmvmm.h maooo H
osmqmu mmz- mmom- ucm>aom mzz easedeoo

 

mQOIAvaImICHNMAHu UHHmeEMmm mo mump AHEQV

M

.mDUSUoumouonm
mocmc0mmu oaumcmme HmmHUSZII.m mamae

16

ll myospoum
Iouonm o>HuommmoH pom mononamvvlmchNMHnulmm mo mnuommm mmszI.H musmflm

 

 

 

 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

g c- 02 91 oo— 8~ o- 8. 9: 09 00 °~ 00~ o- on. 9" 09
_ >h»L»L.»»iL>>lF»F>P» r-hpppirb».—»sh.»>LL _r»»Li° rLih..»lF»rF+»»rh_iF »
4. AA 44.1 1nd# #4 1% . i—Li 13 4 AH A_.1i._i 4a #4441 j A _
t _
Ian
I
Evan—Omn— FUDQO~E A?
:3
hUDoOzm
:8 no 8 no to.
a
I w 1
.8~ ' .8- | 8—
U U
{E .8 .0
Dow Ohm OO— 9‘ 00‘ 00 O~
rih._rkbh».-pbrulpyp then
1 0\E
. 44 fl 1g<figflng H 4— 3 02 02 02 02 2: o: o2 3 2
hhhp Flrlrtrbppie.>p1.e.l~»>>»>.k..>b» O
I j a. 33.: A
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.9
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kmn o Skew I?
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198

'Jul

l7

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Figure 2.--Infrared spectra of 35ftriazin-5(4H)-ones
I-III and respective photoproducts IV-VI

CONCLUSIONS

The photolysis of I-III under a wide range of
reaction conditions and at wavelengths greater than 290 mn
indicates the potential environmental significance of such
non-biological degradations. Determination of photoproduct
formation and residual level in the field would dictate
toxicological evaluations and analytical procedures neces-
sary to studies of its occurrence and ecological "burden."
These particular triazinone photoproducts ("deaminated"
compounds) are considerably less effective biologically

than their corresponding parent compounds (Waggoner, 1971).

18

LITERATURE CITED

Calvert, J.G., Pitts, J.N., Jr., "Photochemistry," pp. 377-
427, 450-475, Wiley, New York (1966).

Crosby, D.G., ACS-Division of Pesticide Chemistry (Pro-
bationary), Paper No. 22, 158th National Meeting,
1969.

Mustafa, A., "Advances in Photochemistry: Volumn II,"
pp. 90, 100, 123, Interscience, New York (1964).

Neckers, D.G., "Mechanistic Organic Photochemistry,"
pp. 109-121, 131—138, 177—184, Reinhold, New York,
(1967).

Padgett, W.M., II, Hamner, W.F., J. Org. Chem., 80, 803
(1958).

Pape, B.E., Zabik, M.J., J. Agr. Food Chem., 18(2), 202
(1970).

Paquette, L.A., "Principles of Modern Heterocyclic Chemis-
try," W.A. Benjamin, New York (1968).

Plimmer, J.R., Kearney, P.C., Klingebiel, U.I., Tetranhedron
Letters, No. 44, 3891 (1969).

Rosen, J.D., Siewierski, M., Winnett, G., J. Agr. Food
Chem., 18(3), 494 (1970).

Smolin, E.M., Rapoport, L., "The Chemistry of Heterocyclic
Compounds: §fTriazines and Derivatives," Inter-
science, New York (1959).

Waggoner, T.B., Chemagro Corp., Kansas City, Mo., private

communication, 1971.

Presented at the joint Conference, CIC-ACS;
Division of Pesticide Chemistry (Probationary); Toronto,
Canada; May, 1970.

19

20

Research supported in part by grants from the
National Institute of Health, Food and Drug Administration,
and Environmental Protection Agency (Grant No. CC-00246-03
and 5ROl FD-00223-05, and 8R01EP-00801-06) and the Michigan

Agricultural Experiment Station.

PART II. SOLUTION-PHASE PHOTOCHEMISTRY OF
SYMMETRICAL TRIAZINES

INTRODUCTION

The photochemistry of s—triazines (Table 1) has
only recently been investigated in detail. Earlier inves—
tigations have demonstrated that photodecomposition occurs
in natural sunlight. In addition, changes in the uv spec—
tra of photolysed solutions and decreases in the phyto-
toxicity of the unidentified product mixtures have been
reported (Comes and Timmons, 1965; Jordan, ei_gi., 1963,
1965). Jordan, ei_§i,, 1970, summarized the literature on
s—triazine photodecomposition to that date.

Recently, Plimmer and co-workers studied the pho-
tolysis of III and IX at 220 nm in methanol solution by
combined glpc—mass Spectrometry. Simazine (III) yielded
IX, XV, and XVIII, and other methylated products: possibly
involving methylation of a ring nitrogen. Photolysis of IX
yielded XVIII and methylated products (Plimmer, personal
communication). Plimmer, gi_ai. (1969) also reported the
conversion of XXII to XV as the result of irradiation of

the solid material.

21

22

TABLE l.—-Authentic g-triazines and photoproducts.

 

R

NA.
AN/‘k

 

 

 

R3HN NHR2
Substituents

S—triazine Designation
R1 R2 R3
Atrazine (I) Cl C2H5 C3H
Propazine (II) C1 C3H7 C H7
Simazine (III) Cl C2HS C H
Hydroxy—Atrazine (IV) OH C2H C3H
Hydroxy-Propazine (V) OH C3 C H7
Hydroxy-Simazine (VI) OH CZH CZH
Atratone (VII) OCH C2H5 C H
Prometone (VIII) OCH C3H7 C3H7
Simetone (IX) OCH C2H5 C H
Iodo-Atrazine (X) CZHS C H
Iodo-Propazine (XI) C3H7 C3H
Iodo-Simazine (XII) C H C H

2 5 2

(XIII) H CZHS C3H
(XIV) H C3H7 C H
(XV) H C2H C2H
Fluoro-Simazine (XVI) F C2H5 CZH
Bromo-Simazine (XVII) Br CZH CZH
(XVIII) OCH H C H

23

TABLE l.--Continued.

 

 

 

Substituents
S—triazine Designation
R1 R2 R3
Ametryne (XX) SCH3 C2H5 C3H7
Prometryne (XXI) SCH3 C3H7 C3H7
Simetryne (XXII) SCH3 C2H5 CZHS
//iiil
/ i
\\ //J\\\
R:3 N R2
(XXIII) C3H.7 SCH3 N3
(XXIV) C3H7 SCH3 NH2
(XXV) C3H.7 H NH2
(XXVI) C3H7 H N3

 

Recent investigations in this laboratory (Pape and
Zabik, 1970) have demonstrated the generality of the photo-
chemical solvolysis of 2-chloro-g—triazines in alcohols and
water between 253.7 and 300 nm. Photolysis of I, II, and
III in methanol and in water yielded VII, VIII, IX, and IV,
V, VI, respectively. These and other product studies were
initially suggestive of a carbonium ion mechanism. The
irradiation of 2-methylthio-g-triazines XX, XXI, and XXII

in hydrocarbon, alcoholic, or aqueous solution resulted in

24

the formation of the 4,6—di(alkylamino)—§ftriazines XIII,
XIV, and XV, respectively. Solvent participation reactions
indicated an intramolecular elimination with hydrogen trans-
fer. Our studies of changes in uv spectra of 2-chloro-g-
triazines under laboratory conditions at 280 nm are identi-
cal to those reported by Comes and Timmons (1965) and
Jordan, gi_ai. (1963 and 1965) in sunlight and support the
conversion of these triazines to their 2-hydroxy analogs
under field conditions. The purpose of the present investi-
gation was to extend the knowledge of the photochemistry of
substituted triazines.

Objectives of these photochemical studies included:
(1) the study of 2-f1uoro-4,6-bis(ethylamino)-§-triazine,
2—bromo—4,6-bis(ethylamino)—§-triazine, and 2-iodo-g-
triazines in methyl alcohol and in water; (2) the photolysis
of 2—azido-4,6-methy1thio-s-triazine; and (3) preliminary
investigation of the significance of photochemical "sensi-
tization" on the fate of the s—triazine system. The more
detailed investigation of the solution-phase photolysis of
2-iodo—s-triazines X, XI, and XII was extended as part of
a study of mechanistic photochemistry: to determine the
kinetic and product specificity influences of the carbon-

two substituents (2—F, Cl, Br, I and 2-OCH OH, H) of

3!
symmetrical triazines. The directions and implications of
considerations of the mechanism of g—triazine N-dealkylation

have been influenced by collaborations with Z. D. Tadic

25

and S. K. Ries who have recently completed work on the

thermal reactions of s—triazines (Tadic and Ries, 1971).

EXPERIMENTAL MATERIALS AND METHODS

S-Triazines

 

Authentic g-triazines I—III, IV—VI, VII-IX, XX-
XXII, XVI, and XVII were supplied by Geigy Agricultural
Chemicals, Ardsley, New York. S—triazines XIII-XV were
prepared photochemically (Pape and Zabik, 1970). The 2-1-
s—triazines X-XVII were supplied by Tadic and Ries, and
were purified to greater than 99.5% purity by column chro—
matography on 100 mesh silicic acid [chloroform-acetone
(9:1)]. Compound XXIII was provided by CIBA Agrochemical
Company, and was recrystallized from methanol until greater
than 99% purity was obtained. Identity was confirmed by

ir and mass spectra.

Solvents
Solvents were of analytical grade. Water used in
photolysis reactions was distilled and had a pH of approxi-

mately 6.5.

Chromatography

 

Column and thin-layer chromatographic (tlc) sepa-
rations of products were accomplished on silicic acid (AR,
100 mesh) and silica gel, respectively. The chromato-

graphic solvent system was chloroform-acetone (9:1).

26

27

Gas-liquid partition chromatography (glpc) was achieved on
a six ft stainless steel column, packed with 5% Carbowax
20-M on 60/80 mesh Gas Chrom Q (Applied Science Labora-
tories, Inc., State College, Pa.). Column temperatures
ranged from 150-220° C. (isothermal conditions) and the

carrier gas flow was 40 ml per minute (prepurified helium).

Instrumentation

 

Infrared (ir) spectra were determined with a Perkin—
Elmer 337 grating spectrophotomer. Ultraviolet (uv) spec-
tra were obtained with a Beckman model DB-G instrument.
The nmr spectra were obtained on a Varian A-60 high reso-
lution spectrometer, using deuterated chloroform, with tms
as an internal standard. Analysis by glpc-mass spectrometry
was conducted on a LKB 9000 gas chromatograph-mass spectrom-
eter. A 6 ft borosilicate glass column of 3% SE-30 liquid
phase on 100 mesh Gas-Chrom Q was used for indirect intro-
duction of samples. Column flow was 40 ml per minute; and

operating temperature ranged from 150—220° C. (isothermal).

RESULTS AND DISCUSSION

2-Azido-4-Isgpropylamino-6-Methy1thio-
S-Triazine

 

 

Irradiation of XXIII in methanol at 253.7 or 300 nm
yielded 2-amino-isopropylamino-6-methy1thio-g-triazine
(XXIV), 2-amino-4-isopropylamino-g—triazine (XXV), and 2-
azido-isopropylamino-s-triazine (XXVI), and unidentified
volatile sulfur compounds. The evolution of molecular
nitrogen was noted during these reactions. The identity of
photoproducts XXIV, XXV, and XXVI was based on ir and mass
spectra (for functional group ascriptions and spectral
correlations, refer to Pape and Zabik, 1970; Plimmer, 35
gi., 1969; and Padgett and Hamner, 1958). Prolonged pho-
tolysis resulted essentially in the total conversion of
XXIII to XXV, indicating that XXIV and XXVI are inter-
mediates in the formation of XXV. The photolysis of XXIII
to XXIV, and of XXVI to XXV, appears to be quite facile--
understandable due to the strong driving force afforded by
the loss of molecular nitrogen (Calvert and Pitts, 1966).

The photolysis of XXIII in carbon tetrachloride
yielded only XXVI. There was no elimination of N2, with
the formation of XXIV or XXV. This is consistent with the

inavailability of a source of reducing hydrogen, and also

28

29

suggests that the elimination of the equivalent of CHZS
with the formation of XXVI is an intramolecular photo-
process. Such an intramolecular process is also consistent
with the data of Plimmer, ei_3i. (1969) which showed that
the irradiation of prometryne (XXI) deposits yielded 4,6-
bis-(isopropylamino)-§-triazine (with the elimination of

the equivalent of CHZS).

2:

N

IN u
H
N3 \N Nc 37H

/ \

30

"Sensitized" Reactions

 

The irradiation of 4,6-bis(isoprOpylamino)-g-
triazine (XIV) in acetone--a triplet sensitizing solvent
which also may participate gig hydrogen abstraction-~at 300
nm resulted in a photoreaction. The identification of prod-
ucts and the generality of such "photosensitized" conver—
sion of g—triazines at wavelengths greater than 290 nm are

being investigated.

2-Fluoro and 2-Bromo-S—Triazines

 

The photolysis of XVI and XVII in a mixture of
methanol and water (1:1) at 253.7 or 300 nm yielded the 2-
methoxy and 2-hydroxy analog (Simetone and hydroxy-
simazine) as the major products. The 2—hydroxy analog pre-
cipitated from solution upon concentration of the final
reaction mixture, while the 2-methoxy analog was isolated
by column chromatography. Their ir spectra were identical

to authentic standards.

2—Iodo-S-Triazines

 

Photolysis of solutions of 2-I-g—triazines X, XI,
and XII (~l mg/ml) in dry methanol, ethanol, and gfbutanol
at 300-360 nm resulted in a progressive discoloration of
solution to a deep brown and the precipitation of a crystal-
line product, purified by filtration and solvent washing.
These precipitated photoproducts of X-XII were determined

to be their respective 2-OH analogs IV, V, and VI (based on

31

comparison of their ir spectra with authentic samples).
The formation of I2 was suggested by uv spectroscopy, and
confirmed by titration with sodium thiosulfate. The pres—

ence of the respective 2-OCH analogs (VII, VIII, and IX

3
in methanol reactions) and the 2-ethoxy and 2—gfbutoxy
analogs formed in their respective alcohols was confirmed
by glpc-mass spectrometry. Analysis of alkyl halides (RI)
was not attempted.

These initial studies suggested the possibility of
a primary photochemical process resulting in the formation
of the appropriate 2—alkoxy compound, with its subsequent
hydrolysis by HI to yield the 2-OH products. The partici-
pation of a solvent-cage/radical-pairing phenomenon in
these processes was suggested by the absence of any detect-
able 2-H compounds in the methanol reactions of X-XII.
Data suggest that the cleavage of the primary products--

the aromatic ethers (2—OR)—-was not an important photo-

chemical process.

The photochemistry of HI, CH I, and gfc H I is well

3 4 9
documented (Calvert and Pitts, 1966). Excitation of HI
involves promotion of a non-bonding halogen electron to a
higher dissociative state (051.0 at 253.7 nm). The
solution-phase photolysis of alkyl iodides is also charac-
terized by dissociation (RI + gg + R1 1), where RI is

translationally and/or vibrationally excited ("hot")--i.e.,

that for the light and heavy dissociative fragments formed

32

photochemically, most of the kinetic energy must be carried
by the light fragment. It might be speculated that the
formation of IV—VI from X-XII could occur as the result of
two photochemical processes: formation of the apprOpriate
2—a1koxy product, and its subsequent attack by a "hot" H1
radical formed upon the photodissociation of HI. Other
experimental evidence does not support such a mechanism.

In another experiment, a solution of XI (~.001
mg/ml) in glass distilled cyclohexane was photolyzed at
300-360 nm to yield V (25%), XIV (70%), and bicyclohexane
(determined by glpc-mass spectrometry). This data is not
consistent with the exclusive participation of a carbonium
ion mechanism: formation of V is explainable in terms of
a simple solvolysis reaction with a trace of water; but
XIV would not be expected if a true carbonium ion mechanism
were Operative: in such a dilute solution it is quite
unlikely that chemical reduction of XI by HI would be sig-

nificant. The operation of a competitive mechanism is

suggested by this data. That the solvolysis reaction in
alcoholic solution is preferred to protein abstraction in
a hydrocarbon medium has recently become evident in rate
studies (Pape and Zabik, unpublished data). Indeed, in a
binary solvent system (cyclotexane saturated with methanol)
XI yields only V and VII on photolysis.

Photolysis of XI was also carried out under differ—

ent conditions during this investigation. Photolysis in

33

CCl4 solution yielded unidentified products which were
separated on tlc: quite likely, some of these included 2-H
(XIV) and 2-X dimerization products. Again, these data
support a competitive, free radical mechanism. Irradiation
of crystalline XI proceeded with discoloration. No prod-
ucts were identified.

The nature of the leaving group appears to be
critical to the rate-determining step. Iodine is an excel-
lent leaving group, and the photolysis of X-XII proceeds
much more rapidly and at longer wavelengths than I-III.

Based on the multiplicity of product formation and
the well documented photochemistry of HI and alkyl halides,
the product—formation reaction of the 2—iodo-gftriazines is
viewed as a free radical/competitive-pathway mechanism
which may involve radical coupling, hydrogen abstraction,
and photochemical participation in the initial (intermedi—
ate) product decay, as well as chemical hydrolysis and

radical trapping. An exclusive free radical photochemical

process of the decay of X-XII would involve the homolytic
cleavage of the triazine carbon-iodine bond to yield the
respective radicals (proceeding gig some unelucidated
excited state). These two radicals would then have three
alternatives: (1) recoupling to yield X-XII; (2) diffusion
out of the solvent-cage to escape recoupling~~necessarily
followed by requisite attack on solvent or solute, most
probably gig hydrogen abstraction; or (3) hydrogen

abstraction and radical coupling within the solvent-cage.

34

m 7::
.923 E
2% 5x zz—J‘K
g A< z :x_< z
\ Z / \ Z__/(
z Z
52 22”
Ba
55:

Z
z :1:
m m

A
'4sz

36

The fact that no XIV was detected in the photolysate
of XI in methanol suggests the participation of a "secon-
dary" radical-coupling/solvent-cage mechanism, where I0
would abstract the hydroxyl hydrogen from methanol to yield

HI + - OCH ° with - OCH and the carbon radical of the tri—

3’ 3
azine ring then coupling to yield VII—IX. It is, of

course, possible that ° OCH could attack X-XII to yield

3
VII-IX (analogous to the base catalyzed solvolysis of 2-
halo-g-triazines in alcohols). Formation of V during the
photolysis of XI is then explicable in terms of the chemi-
cal or photochemical (Hi) hydrolysis of VIII: although it
is intuitively more attractive to consider the hydrolysis
to be chemical under these reaction conditions, kinetic
experiments are underway to remove this ambiguity. The
homolytic, free radical decay of X-XII, and participation

in competitive pathways is required in the CCl4 solution-

photolysis of XI. The formation of XII-XV is explicable

in terms of the chemical reduction of X-XII by H1, or
trapping of the triazinyl radical by HI (Calvert and Pitts,
1966). The radical may also be trapped by iodine (an even
more efficient trapping agent than HI): iodine formation
arising from the photodissociation of HI and alkyl halides.
Under condensed-phase conditions, Hi may participate in the
reduction of X-XII or in the cleavage of VII-IX to yield

products.

37

The photolysis of X—XII to yield IV-VI and VII-IX
in methanol might be expected to proceed gig a mechanism
analogous to that of the 2—chloro-grtriazines--i.e., those
data having been suggestive of a heterolytic cleavage of
the carbon-chlorine bond to yield the carbonium ion. How—
ever, the multiplicity of these X—XII reactions in longer
chain alcohols, in CC14, and in the crystalline state

necessitates a free radical pathway.

2-Chloro-S-Triazines

 

Irradiation of solutions of I—III in g—butanol,
gfoctanol, and g—decanol at greater than 290 nm (borosili-
cate glass) and analysis of the photolysate by combined
glpc-mass spectrometry demonstrated the formation of mul-
tiple triazine photoproducts: such product multiplicity
requires a free radical mechanism. The glpc data indicated
that the complexity of the product mixture increased with
the length of the carbon chain of the alcoholic solvent
used in the reaction. The dechlorinated and carbon-two
g—alkoxy products of I-III have been definitively identified
in these reactions. The classical mass spectral fragmen-
tation patterns exhibited by these long-chain gfalkoxy-gf
triazines is striking (Figure 1). Other products have glpc
characteristics and mass spectra suggestive of hydroxylated
alkyl and ring-substituted addition products. The photolysis
of XVI-XVII under similar conditions yielded essentially

identical results.

38

wvr

sol

60‘.

96

204.

 

 

 

 

 

20 60 100 140 180 220 260 300 340 380 420 460
tn/e

Figure l.-—Graphical representation of mass spec-
trum of 2-g:decoxy-4,6-bis (isopro-
pylamino)-g—triazine (70eV)

39

The original interpretation of the photolytic data
of I—III in methanol: (1) no evolution of HCl and (2) VII-
IX as the major mechanistic product, which suggested the
ionic mechanism, must be reinterpreted in terms of these
new data. These original data are explicable in terms of
(l) solubilities of HCl in alcohol solution; (2) formation
of the hydrochloride salt of the 4,6-di(a1kylamino) groups
of I-III or VII-IX; and (3) a selective radical-coupling/

solvent-cage preference for the formation of the carbon-two

 

methoxy product, analogous to that noted in the reactions

of X-XII.

Photochemical Dealkylation

 

An interesting correlation has been noted between
the uv spectroscopy and photochemistry of getriazines and
recently noted thermal dealkylation reactions (Tadic and
Ries, 1971). Tadic and Ries propose a cyclic transition
state (Chugaev reaction) in these monomolecular dealkyla-

tions of 2-F, Cl, Br, I, OCH -4, 6-di(a1ky1amino)-gh

3

triazines. The results of Plimmer (1969), which demonstrated

 

the occurrence of N-dealkylation reactions at 220 nm are
consistent with the participation of an analogous cyclic
transition state: (see Chugaev-type reaction mechanism,
p. 45). S-triazines have A max in the 220 nm region of
the uv--ascribed to a n + n* transition of C=N of the ring
(Pape and Zabik, 1970). A six-membered cyclic transition

state would favor such a reaction.

 

4O

 

 

CONCLUSIONS

Consideration of the uv spectroscopic data of our
earlier study and comparison with data of the gftriazine
photoconversions reported by others in natural sunlight
suggests that the hydroxylation of 2-chloro-g—triazines to
yield the 2-hydroxy analogs occurs in sunlight. The present
investigation indicates that the products of gftriazines
formed upon photolysis depends not only on the nature of
the carbon-two substituent, but also upon subsequent photo-
chemical/chemical reactions. The conversion of X-XII to
IV-VI, apparently proceeding gig an alkoxy intermediate
(VII-IX), indicates the generality of these photolytic
solvolyses of 2-halo-g—triazines in alcoholic solvents.
Further studies are indicated to elucidate the role of
solvent participation and competitive mechanisms. The par-
ticipation of a Chugaev-type cyclic transition state in the
photochemical N-dealkylation reactions of a variety of g-
triazines is suggested by uv, photochemical, and thermal
data. The kinetics and excited states of these N—
dealkylations are being investigated. The facile photo-
decomposition of XXIII is expected to occur under field

conditions to yield XXIV, XXV, XXVI, N and volatile

2!

41

 

42

sulfur compounds. The hydrogen substitution at carbon-six
appears to be intramolecular. The photochemical "sensiti-
zation" of the g—triazine ring is indicated as a possible
avenue for the further degradation of metabolic and photo-

lytic products (2-hydroxy and 2—H analogs).

LITERATURE CITED

LITERATURE CITED

Calvert, J.G., and Pitts, J.N., Jr., "Photochemistry,"
p. 474, John Wiley and Sons, Inc., New York (1966).

Comes, R.D., and Timmons, F.L., Weeds, ii(2), 81 (1965).

Jordan, L.S., Day, B.E., Clevx, W.A., Res. Progr. Repi,
Western Control Conf., 78 (1963).

 

Jordan, L.S., Farmer, W.J., Goodin, J.R., and Day, B.E.,
"Residue Reviews, Vol. 32, The Triazine Herbicides,"
p. 267, Springer-Verlag, New York (1970).

Jordan, L.S., Mann, J.D., Day, B.E., Weeds, ii, 43 (1965).

Padgett, W.M., II, Hamner, W.F., J. Org. Chem., 89, 803
(1958).

Pape, B.E., and Zabik, M.J., J. Agr. Food Chem., i8, No. 2,
p. 202 (1970).

Plimmer, J.R., Kearney, P.C., and Klingebiel, U.I., Tetra-
hedron Letters, No. 44, p. 3891 (1969).

Plimmer, J.R., U.S.D.A., Beltsville, Md., Personal communi-
cation (July, 1969).

Tadic, Z.D., and Ries, S.K., J. Agr. Food Chem., i2, No. l,
p. 46 (1971).

Presented at Joint Conference, CIC-ACS; Division of
Pesticide Chemistry (Probationary); Toronto, Canada; May,
1970.

43

 

44

Research supported in part by grants from the
National Institute of Health (Grant No. CC-00246-03 and
5R01FD-00223-05) and the Environmental Protection Agency
(Grant No. 8R01-EP-00801—06), and the Mighican Agricultural

Experiment Station.