NOVEL GLYOXYLATES AND HERBICIDAL AND PLANT GROWTH REGULANT ACTIVITY OF GLYOXYLATES

NOUVEAUX GLYOXYLATES ET ACTIVITE HERBICIDE ET DE REGULATION DE LA CROISSANCE DES PLANTES DES GLYOXYLATES

English Abstract

12H-dibenzo[d,g] [1,3]dioxocin-6-carboxylic acid and certain
derivatives thereof (glyoxylates) exhibit plant growth regulant and herbicidal
activity when applied to a plant locus.
(see figure I)

Claims

-89-
CLAIMS:

1. A method of inhibiting the growth of undesirable vegetation which
comprises contacting said vegetation's locus with a herbicidally effective
amount of a compound having the formula
Image
wherein:
A is COOR, COSR, CSNH2, CN or, together with one of B,
-C(=0)0-;
R is H, Na, K, di(C1-C4)alkylammonium, diethanolammonium, C1-C8
alkyl, C2-C8 alkoxyalkyl, cyclohexyl, tetrahydrofurfuryl or
dimethyldioxolanylmethyl;
Z is H or CH3;
B is H or, together with A, -C(=0)0-;
Y is H, C1-C4 alkyl or alkoxy, CF3 or X; and
X is F, Cl or Br,
provided that where more than one of Y is other than H on either ring they
must be in the 3, 4, 8 and/or 9 positions and, where Y is in the 1, 2, 10 or
11
positions on the rings, no more than one of Y is other than H and that one Y
is
CH3.


-90-

2. A method as in claim 1 wherein Y, B and Z are all H.
3. A method as in claim 1 wherein B and Z are all H.
4. A method as in claim 1 wherein Y and Z are all H.
5. A method as in claim 1 wherein Y at the 1, 2, 10 and 11 positions, B
and Z are all H.

Description

NovEL GLYOXYLA'TES AND IIERDIC.IDAL AND PLANT GROWTH
.,~~v REGULANT ACTIVITY OF GLYOXYLATES
2035024
BACKGROUND OF THE ItdVEN'fIUN
The invention relates broadly to
1211-dibenzo[d,g] [1,3]dioxocin-G-carboxylic acid and
certain derivatives thereof, generally referred to herein
as "glyoxylates", and their use as plant growth regulant
and/or herbicidal agents and more particularly to their
use, usually in combination with appropriate carriers and
surfactants, in influencing the growth and development of
crops, ornamentals and turt grasses.
Some of the compounds which find utility in the
present invention are known generically, and specifically
in the case of the methyl ester, from U.S. Patent
3,553,234. Therein, a class of compounds described as
12H-dibenzo[d,g][1,3]dioxocin-G-carboxylic acids and
their esters and Having the formula
x r
--v
/ ~a
0
~, r
x r
wherein X and Y are hydrogen or a halogen and R is
hydrogen or lower alkyl are disclosed to have utility as
:r:.



1f() 91/8(1(109 fC'1-/US98/83G72
.. _ ?. _
2035024
hypolipidemic agents for warm blooded animals. Also
mentioned are the pharmaceutically acceptable salts of
such acids. An improved class of hyf~olipidemic agents
are disclosed by the same inventors in U.S. Patent No.
3,947.,173 wherein ca:rboxamides are also contemplated.
however, no utility in the agricultural field is
suggested, and on tests of the specific compounds
disclosed in U.S. Patent No. 3,553,234 and U.S. Patent
No. 3,941,173 no herbicidal activity was found.
The present invention is based upon the
discovery that a selected group of such compounds
pos:aesses unexpected activity when employed as plant
growth regulant and/or herbicidal agents at controlled
dosages, while other closely related compounds within the
genus of U.S. Patent 3,553,234 display no significant
agrochemical activity.
As used herein, "plant growth regulant" means
a compound or composition which affects the maturation
and metabolism of plants. hence, a "plant growth
regulant" has many effects on plant growth. tfowever, not
all plant growth regu:Lant active compounds affect plants
the same way. For example, they could affect vegetative
growth by retarding or stimulating terminal growth,
and/or stimulating side branching and could inhibit new
growth such as the developmen t of new sprouts of woody
plants, the sprouting of tubers and rhizomes and the
development of sucker growth. Such regulants could
affect flowering plants by eliminating early flowering,
by thinning of blossoms oz- by increasing the number of
flowers. Fruit-bearing trees and bushes could be
affected by increases in the number, size and quality of
the fruit, by producing seedless fruit, by accelerating



V'() 91 /1)(10(19 I'Ch/US90/03(r72
.,~ _
2Q35024
senescence and fruit ripening. Doth flowering and fruit
plants could be affected by accelerating plant dormancy
and maintaining bud dormancy. n "plant growth regulant"
could cause selective postemergent control of weeds by
reducing their vigor and competitiveness, and thus
prevent their spread and stop normal seeding.
Some specific applications of plant growth
regulants include:
preventing lodging of cereals;
increasing production of harvestable tea leaves
by promoting side branching;
inhibiting sprouting of potatoes and onions in
storage;
suppressing growth of grass, trees, shrubs, and
other vegetation in decorative lawn areae~, parks, golf
courses and along highways and other rights-of-way;
accelerating fruit ripening and thus, aiding
mechanical harvesting by a single or reduced number of
pickings;
2U defoliating cotton to permit mechanical
harvest;
inhibiting new growth of defoliated cotton and,
thus, reducing staining of fiber during mechanical
harvesting;
increasing the quality of the hax-vested crop,
e.g., sugar content of sugar cane, sugarbeets,
grapefruit, grapes, and ottrer fruits;
aiding mechanical harvesting of nut crops by
accelerating ripening, stimulating husk cracking and
promoting abscission;
protecting crops from drought;




. .
~:
protecting fruit crops from frost by stimulating early dormancy
and/or preventing premature breaking of dormancy;
increasing latex flow of rubber;
increasing frost resistance of winter cereals;
reducing the flowering or bolting of lettuce, sugar beets and
tobacco;
controlling tobacco suckering;
stimulating increased fruit set of soybeans, peanuts, cotton,
tomatoes, melons, and other fruits and
enhancing fruit color and quality;
stimulating branching of pot plants; e.g. heather, azalea,
chrysanthemum and geranium;
growth retardation in pot plants, e.g. poinsetta, petunia,
chrysanthemum and azaleas;
stimulating branching of young fruit trees, e.g. apple and pear.
"Plant growth regulant" also means the retardation of terminal (i.e.
vertical) growth of plants. In grasses and weeds, this regulant activity will
retard the grass height and, hence, grass growth. In bushy plants, on the
other hand, the resultant retardation of terminal growth by the regulant
activity
often results in enhancement of lateral growth, an effect desired, e.g. in
tomato plants.
SUMMARY OF THE INVENTION
According to an aspect of the invention, a method of inhibiting the
growth of undesirable vegetation which comprises contacting said
vegetation's locus with a herbicidally effective amount of a compound having
the formula
C




-5-
2035024
Y4
'A
'~-Z
O
Y.~
wherein:
A is COOR, COSR, CSNH2, CN or, together with one of B,
-C(=0)0-;
R is H, Na, K, di(C~ - C4)alkylammonium, diethanolammonium, C~ -C8
alkyl, C2 -C$ alkoxyalkyl, cyclohexyl, tetrahydrofurfuryl or
dimethyldioxolanylmethyl;
Z is H or CH3 ;
B is H or, together with A, -C(=0)0--;
Y is H, C~ -C4 alkyl or alkoxy, CF3 or X; and
X is F, C1 or Br,
provided that where more than one of Y is other than H on either ring they
must be in the 3, 4, 8 and/or 9 positions and, where Y is in the 1, 2, 10 or
11
positions on the rings, no more than one of Y is other than H and that one Y
is
CH3.
n



1f() 91/llllllllg 1'CI~/US90/03G72
"' -6-
20~5024
There has further been found a method of
controlling the growth of undesired vegetation, which
method comprises applying to the vegetation locus,
especially by postemerc~er~t: application, a herbicidally
effective amount of a compound having the same formula as
above.
There has still further been found a
composition of matter useful in the regulation of plant
growth and development, which composition comprises a
compound having the same formula as above, an inert
carrier and a surfactant.
In one preferred embodiment of the foregoing
methods and composition of.- the present invention, Y, B
and Z are all Ii, resulting in a compound having the
formula
/~o
a
In a furtl~ri- embodiment of the foregoing
mettrods and composition of ttie present invention, B and
Z are all Ii, resulting in a compound having the formula
Y
~ 10
r--A
~O
m
Y



1f() 91/0(1009 I'C1~/US911/03fi72
.-. _7-
2035024
In yet another embodiment of the foregoing
methods and composit:l.ons, Y and Z are all H, resulting in
a compound having the formula
/--o
a
0
The invention also encompasses certain novel
compounds having herbicidal and/or plant growth
regulating activity having the formula
~Y~
.~ a A
~' ~ z
0
''' ~ r.
wherein:
A is COOK, COSR, CONK' R" , CSNIIZ, CN or,
together with one of B, -C(=0)0-;
R is CZ - C'8 alkoxyal.kyl, cycloalkyl, Cz - C4
hydroxyalkyl, (alkoxycarbonyl.)alkyl, dialkylaminoalkyl,
tetrahydrofurfuryl and dimethyldioxolanylmethyl ;



wo mnooo<~ rcriuS~oio3t,~2
2Q35024
R' and R" tnay be the same or different, and
each is a member selected from the group consisting of ti,
lower alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl,
or alkoxycarbonylalkyl.; or NR'R" taken together represent
a saturated monocylic heterocyclic group such as
pyyrolidino, piperidino, morpholino, piperazino or N-
(lower alkyl)-piperazino;
Z is H, CFi3, CIi3S, C~i3S (O) or COOR;
B is II, lower alkyl, lower alkoxy, hydroxy,
benzyloxy, acetoxy, (=O), or, together with A, -C(=O)O-;
Y is H, C~ - C4 alkyl or alkoxy, CF3 or X; and
X is F, C1 or Br;
provided that where more than one of Y is other than Fi on
either ring they mu~~t be in the 3, 4, f3 and/or 9
positions and, where Y is in the 1, 2, l0 or 11 positions
on the rings, no mora than one of Y is other than H. In
other embodiments, no more than one of Y is other than FI
on either ring.
Another group of novel compounds within the
scope of the invention has the formula
'Y"
~O
A
Z
0
WherC,'lIl:


~f() 91 /(IU11(19
I'C.'1~/US90/03(72
035024
2
A is COOK, COSR, CONR'R", CSNHZ, CN or,
together with one of B, -C(=0)O-;
R is Ii, Na, K, di (C~ - C4) alkylammonium, N(3
amino-propyl)N-oleylarnmonium, C~ - C8 alkyl, aryl,
heteroaryl, CZ - Ca alkoxyalkyl, Cz - C4 hydroxyalkyl,
(alkoxycarbonyl)alkyl., dialkylaminoalkyl, cycloalkyl,
tetrahydrofurfuryl oz- dimethydioxolanylmethyl ;
R' and R" may be the same or different, and
each is a member selected from floe group consisting of 11,
lU lower alkyl, cycloalkyl, aryl, heteroaryl, heteroalkyl,
or alkoxycarbonylal.kyl; or NR'R" taken together represent
a saturated monocyli_c heterocyclic group such as
pyyrolidino, piperidino, morpholino, piperazino or N-
(lower alkyl)-piperazino;
1' Z iS Ii, CI(3, CIi3S, CI13S (O) , COOR;
B is Ii, lower ~7.kyl, lower alkoxy, hydroxy,
benzyloxy, acetoxy, (-O), or, together with 11, -C(=0)0-;
Y and W are C~ - C4 alkyl or alkoxy or CF3;
m and n are o-2 and the sum of m plus n is 1-4.
2o By way of illustration, and not by way of
limitation, the following are moieties suitable for use
as 11, Z, B and Y in the compositions of the present
invention.
As examples of moieties suitable for use as A
25 mention may be made of a carboxyl group (-COOFi), simple
esters such as:
COOCH3
COOCIiZCH3
COOCH2CHzCII~
3 0 COOCIi ( CI(3 ) 2
COOCIIZCIiZCIizCII3
COOC ( Cli3 ) 3


l1'() ~) I /11()009
I'CI'/US9f1/03(>72
'"~.. -10 - '
COOCIIZ ( Cfiz ) bCH3
COOCHzCH ( CIIZCH3 ) CIiZCH2CIiZCH3 ~ ~ 3 5 0 2 4
COOC6H>
COOC6Ii5
substituted esters such as:
COOCHZCHZOCIi3
COOCHZCIizOCIizCiizCIizClI3
COOCHZCIi (01i) CIIZOII
O O
1 o coocIIZcIi-cliz
COOCHZ
O
COOCH ( CII3 ) COOCIiZCII3
COO CIiZCii2N ( CI I3 ) 2
COOCHzCIi2N ( CII3 ) Z . iiCl
amides such as:
CONHZ
CONIiCH3
COIiNC6H5
2 0 CON ( CH3 ) Z
salts such as:
COONa
COOK
COON . ( CI I3 ) 21JI i
2 5 coon . ( IiOCIi2ct12 ) zNII
COOII. CII3 (CIiz) ~CIi=CIi (CI12) aNIiCIizCIi2CIizNII2
and other moieties such as:
CI I20Fi
CIizOSO2C61-i6-CII3-4
30 CH (OIi) CN
CIi=CIiCOOCIiZCli3



wc~ <mnuouv rctvusooin3~~~z
-11-
CN
C (=S ) Nfiz
C (=O) SCHZCFF3 2 0 3 5 0 2 4
C (=O) NHNHZ.
Z may be:
FF
CH3
CH3S
CIi3S (O)
C (=O) OCH2CII3;
F3 may be:
Ii
CH3
( CFi3 ) 2
CHZ=
CH3CH2
( CH3 ) ZCH-
C6H5-
C F3
2 0 FFO-
CFF30-
C6H5-CIi20-
CIi3C (=O) O-
=O
2 5 -CHz-O
( CH3 ) ZCHCOC ( =O ) -
lactone (B -+- A) ; and
Y may be:
H
3 0 CH3



Vii'( ) ') I /(IU11119
-12-
( cli3 ) 3c
r
I'C: f/US9(1/(13072
cl
Ii0
CIi30 2 0 3 5 0 2 4
C6Ii5CIiZ0
CIi3C (=O) O
NOz
a nitrogen ring structure such as pyridine
derivatives.
These and other aspects of the invention will
become clear to ote ski.ll.ed in the art from the
specification and claims that follow.
DL_I_nII~EU I~F~.SCFtIPTIO_N
When used in the present invention, the terms
"plant growth regulant" or "plant growth regulating
effect" refer to the ability of a glyoxylate, when
applied to a plant locus, to influence the growth and
development of useful crops, ornamentals and turf as far
example described by illustration hereinbefore. A
variety of effects may be obtained depending upon, among
other considerations, the plant in question, the
glyoxylate selected and the manner., amount and timing of
application. Generwally the result obtained by
application of a glyoxylate is the desirable promotion,
inhibition and/or alteratian of a plant's physiological
or morphological processes, such as accelerating or
retarding leaf, shoot and root growth, reduction in
stature, increased branching, tillering, terminal
inhibition, inhibition of regrowth after pruning thereby



1V() 91 /1)(1(1(19 I'C f/US90103G72
2 0 3 5 0 2 4 -13-
reducing the need for follow-up pruning, increased root
growth, delayed budding, increased bud count, yield
increases, etc. In particular, the glyoxylates of the
present invention have been found to be effective growth
retardants when applied to turf grasses such as,
perennial rye, red and tall fescue and Kentucky
bluegrass. A further example of a plant growth
regulating effect is the ability of a glyoxylate
compound, when timely applied (preferably in the second
or third growth stage) to act as a straw shortening agent
on wheat, an especially useful effect where high nutrient
levels are employed to increase grain yield.
The use of tyre tei-rns "herbicide" or "herbicidal
effect" refers to the application of a glyoxylate
compound to kill, or at least substantially inhibit the
growth of, an undesired plant. Especially significant
examples are the use of one of the glyoxylates to control
the growth of weeds, including grassy weeds, in wheat and
reduce flowering in bolting weed beets. The glyoxylates
have been found to be particularly useful in controlling
the growth of the generally hard to control sedges,
especially yellow nut sedge, when applied to the soil in
which the nut sedge tubers are beginning to germinate.
The compounds useful herein are those having
the formula
.Y,
p A
Q Z
Y~




-. -14-
2035024
Each of the defined glyoxylate°compounds has
been found to have a herbicidal'and,~or plant growth
regulating effect. In. addition to activity and
selectivity considerations, a particular ester orv salt
form of a glyoxylate will often wbe chosen for its
convenience of handling and applicatiTon, an example being
the choice of the n-butyl ester, which has~~reduced
volatility, over the methyl ester form: On the other
hand, where volatility is desirable, e.g., for
to application by fumigation (smoke bombs) in a greenhouse
to induce branching of ornamentals, compounds such as the
nitrile and lower esters (e.g. , methyl, ethyl and prQpyl)
which are more volatile, may be preferred.
The choice of substituents to=be placed on the
benzene rings, on the other hand, seems 'to affect the
nature and extent of plant growth regulating effect to be
obtained and such substitution is limited with respect to
(1) the identity -of the substituent=(2~~ location on the
ring or rings and (3).. number of substitutions that may be
accommodated. Substitution opportunities are
particularly limited when placed in the l, 2, 10 and 11
positions according to the following number system:
3
2 4
11
~O
12
O
11
i
9
,.., , ... n..~.



11'() ~ll/(111(llly 1'(.'1~/tl5')(1/1).1G71
'.
-15-
2035024
In such cases, rubstit:utiott of ~ methyl group
at no more than one position has been found possible
without <a significant loss of lterbi.cidal activity.
5ubstituent possibilities at the remaining benzene ring
positions (3, 4, E3 and 9) , i.tt order to vary the growth
regulating and/or lm-~rlric.Ldal effect obtained without:
significant overall loss of activity, are more numerous.
Witi_le it i.s preferred tatot_ trot more than one position ort
either ring be subs~.:itut.c~cl, the cltoic:e of substituents
may be increased as def.ittect 7bove.
Generally the d:lyoxy.lattos wil_1. he applied to
the plant locus as the active ittdredient irt a composition
also cotnl~rising a carrier. and .~ surfact:ant, that is, a
dispersing, emulsify:ittg or wetting agent, although
dil.uents, extenders rtnd outer active i.ngredi.ents having
a differing or cotnp.l.eumntt:ttt:~y uti.lit:y may be present. The
compositions may thus be in ttte form of finely divided
particulate solids, gr.attuletx, wettable powders, solutions
and dispersions.
i'he inert canri.or may be solid (e.g. , clays,
natural or synthetic silicates, talc;) or. :liciui.d (e.g. ,
water, alcoltols, esters, ar.omati.c hydrocarbons, petroleum
fraction;) . 'fhe surface active aqertt:s may be anionic,
cationic: or non-i.otic (e.g, , salts of lignosulfonic
acids, alkyl-aryl sulfonic acids, acetates of alkylamines
attd condettsates of et lty.lmte oxide with fatty alcoltols ou
acids) . In addition, tltc~ compositions may contain
thickeners, adttes.ivc»;, rt:alt.i.l i_zers, preservatives and
other ad juvants known to the art.
Tlte glyoxy.l ates may be applied by conventional
tecltniciues (e.g. , slotvead.i.ng, dusting or ~:laz-ayirtg or via




-1s- 203502 4
fumigation smoke bombs in confined areas such as greenhouses) in a variety
of forms (e.g. , solutions, suspensions, wettable powders or granules).
The compositions of the present invention generally will contain from 5
to 95 percent by weight of the active glyoxylate compound and will be applied
at a rate of from 0.5 to 4 kilograms per hectare, when used as herbicides.
While in a plant growth regulating composition the amount of active ingredient
may be comparable, the amount employed will vary greatly depending upon
the particular glyoxylate chosen and the effect in question, generally ranging
from 0.01 gram to 4 kg per hectare. Conveniently, such applications are
obtained by spraying a solution containing from 0.1 to 500 ppm active
ingredient to run-off, depending on the plant species to be treated.
Some of the compounds which are the subject of the present
invention are derived from the acid form which may be prepared by methods
known to the art, for example, according to the teachings of U.S. Patent
3,836,543.
Modifications and variations of these procedures where benzene ring
substituents are other than those described in the '543 patent and where
substitution is desired at the 12 position, are shown in the examples below.
Thereafter they may be converted to the final form generally according to
methods also known in the art, for example, conventional esterification when
preparing a lower alkyl ester.
In order that those skilled in the art may more readily
understand the present invention and certain



WU 91/(IOIIU9 1'Cl'/US90/03G72
-17-
203502 4
preferred embodiments by which it may be carried into
effect, the following specific examples are afforded.
PREflIRATIONS
l2ti-Dibenzo f d a 1 f ~ 3 1 diox_ocin~6= carboxyl is ac~.d
Into a 1?. liter 3-neck flask fitted with an
air-driven overhead stirrer and a condenser are placed
2,2'-methylene bisphenol (200.24 gram, 1.0 mol), 4 liter
of isopropyl alcohol and then potassium carbonate (552.84
gram, 4.o mol), while stirring. Dichloroacetic acid,
(82.5 ml, 1.0 mol) is added over a period of 2 minutes.
During tire addition of the dichloroacetic acid some
effervescence is observed. The reaction mixture, which
is a white, easily stirred, heterogenous mixture, is
heated at reflex and stirred vigorously. lifter 24 hours,
the reaction mixture is cooled to room temperature and an
additional 82.5 ml (.1.0 mol) of dichloroacetic acid is
added. Again, some effervescence is observed. The
reaction mixture is then heated at reflex fox an
additional 72 hours. 'Total reflex time is 96 hours.
After 48 hours of total reflex time, the reaction mixture
thickens and vigorour3 stirring is maintained.
Once the 96 hour reflex period is complete, the
condenser is replaced with a distillation head and 200 ml
of isopropyl alcohol is distilled off at atmospheric
pressure and replaced with 200 ml of H2o. This is
repeated until they distillation temperat~.ire reaches
95-100'C. During the distillation procedure, once H2o is



1f!) 91/(Ifll)U9 I'C'F~/US90/03C72
"" -18-
2035024
added, the reaction mixture becomes much more fluid and
eventually a reddish brown homogenous solution is
obtained. After the distillation temperature reaches
95-100°C, the reaction mixture is cooled to room
temperature. Upon cooling, solids form, therefore it is
important to maintain vigorous stirring. The reaction
mixture is then made' strongly acidic by the careful
addition of concentrated FIC1 (800 ml) over a period of
1-2 hours. Extreme caution must be taken during the
addition of the FiCl because of effervescence. The
effervescence is particularly vigorous during the latter
stage of FiCl addition. Once tl~e IiCl has been added, the
reaction is stirred an additional 2 loours at room
temperature. The so7..ids are collected by filtration and
washed well with FFzO.
These solid: are then placed in a separatory
funnel with 2 liters of ethyl acetate and 2 liters of ltd
HC1 and shaken vigorously. The organic layer is
separated, washed with brine, dried over. MgSO4 and
concentrated. The so:Lids obtained are then dried in a
vacuum oven to afford 239 grams (93 percent) of crude
product as a brown-tarr solid, which are them placed in a
Soxhlet extraction aploarat:us and exhaustively extracted
with refluxing cyclolrexane (2 liters). Periodically the
cyclohexane solution is cooled and the precipitated
product collected by filtration. The rate of the
extraction depends on how vigorously the cyclohexane
refluxes and recycles. There is obtained 147 grams of
l2Fi-dibenzo[d,g][1,3]dioxocin-6-carboxylic acid as a
white solid: mp 153-157°C; IR (KF3r) 5.78, G.76, 6.93,
8.12, 10.1, 13.1 cm~~; rFi NMR (60 MFFz, DMSO-db) 3.64
and 4.38 (2d, 2, CHZ) , 5.U9 (s, 1, CFi) , 6.9-7.6 (m, 8,



~'~'() 91/fl()11I)9 fC7'/US911/(?3fi72
2035024 19-
Ar-Ii); greater than 99 percent purity as determined by
liquid chromatography.
~F3utv1 12H-Dibenzo f cl~g~]._~~~ 1 dioxocin-6-carboxvlate
Into a 500 rnl round bottom flask flitted with a
stir bar and a Dean-Stark apparatus is placed 111.4 grams
of crude (87 percent) 1.211-dibenzo[d, g~ [ 1., 3 ]dioxocin-6-
carboxylic acid i.n 300 ml of 2:1 n-butanol:toluene. The
mixture is stirred at room temperature for 15 minutes to
l0 effect the complete dassoltrtion of the acid.
COr7Ce11trated sulfuric acid (4.0 ml) is then added and the
reaction mixture is heated to reflux. Immediately upon
attaining reflux, an aqueous layer begin s to separate out
in the Dean-Stark apparatu s. After 2 hours at reflux, no
additional water formation is observed and the reaction
is cooled to room temperat=ure with a cold water bath. A
total of 10 ml of water is collected, the majority of
this water being formed i.n the initial. 30 minutes of
reflux. The cooled reddish-yellow reaction solution is
diluted with 200 ml of toluene, washed with 300 ml of
water, 300 ml of saturated aqueous NaIIC03, 300 ml of
brine and then concentrated under reduced pressure on a
rota-vap. Toluene (200 ml) is added to the residue and
the solution again is concentrated under reduced
pressure. This evaporation with toluene facilitates the
removal of n-butanol. The residue obtained :is taken up
into 300 ml of 2:1 toluene:ether and washed with 200 ml
of 5 percent NaOIi. I)rine, 50 ml, is added to break up
the emulsion that forms with the 5 percent NaOIi wash.



1V() 9(/()(1009 I'Cl~/I.ISyp/U3fi72
,..- - 2 0 -
2035024
The organic solution is then washed with 200 ml of brine,
dried over MgSO4 and concentrated under reduced pressure
to afford a thick light reddish-yellow liquid (130
grams). This liquid i.s then subjected to vacuum
distillation, using a Claisen adapter as the distillation
head and an oil bath for heating. Care is taken during
the course of the distillation to avoid solidification of
the product in the distillation condenser. 11 fore run ( 11
grams) is collected !raving a b.p. 70°C to 17U°C at 0.25
mm. Pure n-butyl ester, 84.3 grams (62 percent) , is then
collected from 171 ° C t:o 1FI0 ° C at 0. 25 mm as a thick clear
liquid which readily solidifies on cooling to afford a
white solid: mp 63-66"C (softening at 60°C); greater
than 99 percent purity as determined by L.C. by
189-195'C/0.4mm; IR (neat) 3.45, 5.75, 6.95, 8.35,
10.4 cm-r; H NRM (60 MIIz, CDC13) 0.9-1.9 (m, 7,
OCHZCHZCIIZCII3 ) , 3 . 4 2 and 4 . G ( 2 d , 2 , CIi2 ) , 4 . 3 5 , ( t , 2 ,
OCIi2CIi2CIi2CFi3) , 5.05 (s, 1, CH) , 7.0-7.4 (m, 8, Ar-H) ) .
Anal. Calcd. for Cr91I2o04: C, 73.06; II, 6.45
Found: C, 73.0; Ii, 6.7
ALE 3
Ethyl l2fi-Dibenzofd glf~.3lc~ioxocin-6-carboxylate
A solution of 1211-dibenzo[d,g] [1,3)dioxocin-6-
carboxylic acid (31.8 grams, 0.124 mol) and conc. HzSOi
(1.6 ml) in 215 ml of ethanol is hreated at reflux,
allowing the condensate to pass through 4A molecular



we ~ o i iuuoo~~ re-w usgoio3~,~2
_21-
2035024
sieves. After ?. hours, the reaction is cooled to room
temperature and 100 ml of methylene chloride is added and
then neutralized by the addition of solid Na2C03. The
salts are removed by filtration and the filtrate
concentrated. The residue is taken up into CH2Clz,
washed with water, 5 percent aq. NaOIi and brine, dried
over MgS04 and concentrated to afford 31.1 grams (88
percent) of product as a white solid: mp 86.5-88.5'C; IR
(KBr) 5. G3, 6.7, 6.88, 7.2, 8.12, 8.98, 9.25, 10.1 cm-~;
~H NMR (6U MHz, CDC13) 1.4 (t, 3, CII3) , 3.43 and 4.6
(2d, 2, CHZ) , 4.42. (q, ?., C~i2CH3) , 5. 1 (s, 1, CH) ,
7.0-7.4 (m, 8, Ar-Ii) .
Anal. Calcd. for C»II~604: C, 71.82; I1, 5.67
Found: C, 71.7; H, 5.8
EXAMPLE 4
Methyl l2li-Dibenzo d~l~ 3.] d~lo~tocin-6-carboxylate
Preparation proceeds as described in Example 3,
only substituting methanol for ethanol. Obtained is a
white solid: mp 10'7-11.0'C; IR (KBr) 5.69, 6.77, 8.2,
9.3, 10.05 cm~~; ~Ii NMR (60 MIIz, CDC13) 3.5 and 4.62
(2d, 2, CIIZ) , 3.98 (s, 3, CIi3) , 5.1 (s, 1, CIi) , 7.0-7.5
(m, 8, Ar-H) .
Anal. Calcd. for C~6H~404: C, 71.10; Ii, 5.22
Found: C, 71.0; H, 5.1



1f()') I /11011(1') i'CI~/US90/03C72
-22-
J.~_XAM F? LE 5 2 0 3 5 0 2 4
n-Pro>'Y1 12H-Dibenzo d,al(1,31dioxocin-6-carboxylate
Preparation proceeds as in Example 3, only


substituting a like quantity of n-propanol for the


ethanol, to obtain a white solid: (KBr)
mp 82-85"C;
IR


5.7, 8.35, 9.4, 10.15 cm~~; ~Ii NMR 0 Mliz, CDC13) 1.05
(6


(t, 3, CIi3) , 1.95 (m, 2, CiiZ~lizCli3)3.47 and 4.65 (2d,
,


2, Cliz) , 4.33 (t, CHZC iizCIi3) , 1, CH) , 6.9-7.5
5.1 (s, (m,


8, Ar-H).


Anal. Calcd. for C~BI(~~U4: C, 72.47; ii, 6.08
Found: C, 72.7; 1i, 6.0
EXIIMPT~E 6
iso-I'robyl 12H-Dibenzofd alf~ 31d o oc'n-6-carboxylate
The subj ect product is prepared as described in
Example 3 , only subsi:it~uting iso-propanol for ethanol ,
yielding a white solid: mp 94-97'C; IR (KBr) 5.73, 6.78,
8.25, 9.05, 9.4, 10.1 cm~~; ~Ii PJMR (60 MII2, CDC13) 1.4
(d, 6, CH-(CH3)Z) , 3.46 a«d 4.6 (2d, 2, CHz) , 5.03 (s,
1, 0-CIi-0) , 5.25 (m, 1, Cf_1(CII3)Z) , 6.9-7.5 (m, 8, Ar-H) .
Anal. Calcd. for C~BII»04: C, 72.47; Ii, 6.U8
Found: C, 72. 4 ; II, 5. 9



CVO ~) 1 /fIU()09 1'L I'/ US90/03G72
- -z3-
EXAMPLE 7
2035024
t-Butvl l2li-Dibenzo [~q7 [ 1 , '~ l~c i ~xocin-6-ca~~oxylate
A solution of 12II-dibenzo[d,g][1,3]dioxocin-6-
carboxyli.c acid (3.0 g, 0.0117 mol) in 45 ml of thionyl
chloride is heated at reflux. After. 4 hours at reflux,
the excess thionyl. chloride is distilled off at
atmospheric pressure and then under vacuum to remove
traces of thivnyl chloride. The acid chloride obtained
is dissolved in 35 ml of toluene and added dropwise over
a period of 20 minutE~s to a solution of t-butyl alcohol
( 15 ml ) containing N, N-dimethylanil ine ( 1 . 8 ml ,
0.01405 mol). After stirring 23 hours at room
temperature, the reaction mixture is concentrated under
reduced pressure and floe re ~idue obtained is taken up
into ethyl acetate, washed with water and brine, dried
over MgS04 and concentrated to yield 3.4 g of a syrupy
residue. Dry column chromatography (elution with 1:4
ethyl acetate-hexanes) afforded 1..57 g (43 percent) of
product as a white solid: mp 94-97°C; I:R (KBr) 5.75,
8.22, f3.7, 9.43, 1Ø22, 13.21 cm-r; ~Ii Nr'IR
(G0 Mliz,
CDC13) 1.6 (s, 9, C(CI-I3)3) , 3.45 and 4.6 (2d, 2, CHZ) ,
4.93 (s, 1, CH) 6.95-7.4 (m, 8, Ar-Ii) .
Anal. Calcd. for Cr9HZ004: C, 73.06; II, 6.45
Pound: C, 73.0; Ii, 6.3



1V() 91/110(!09 I'CT/US90/I?3672
-24-
.-.
~XhM LE 8
2035024
n-Octvl 12H-Dibe o djg,]_["~, ~ l~ioxocin-6-carkJOxylate
12H-Dibenzo[d,g][1,3]dioxocin-6-carboxylic acid
(4.o g, 0.0156 mol) anc:i 45 ml of thionyl chloride are
refluxed/distilled as i.n Example 7. The acid chloride is
then dissolved in 5o ml of toluene and added dropwise
over a period of 10 minutes to a soJ.ution of n-octyl
alcohol (20 ml) containing triethylamine (2.0 ml,
0.0187 mol). After stirring 20 luours at room
temperature, the insolubles that form are filtered off
and the filtrate concentrated under reduced pressure.
The residue obtained is taken up into CIiCl3, washed with
HZO then brine, dried over MgS04 and concentrated. The
residue obtained is purified by dry column chromatography
(elution with 1:10 ether-petroleum ether) to afford
4.18 g (73 percent) of product as a clear syrup; IR
(neat) 3.42, 5.63, 6.71, 6.87, 8.95, 10.1 cm~~; tIi NMR
(6U Mliz, CDC13) 0.9-2.0 (m, 15, OCIiZ (Cliz)6(CH3) ) , 3.48
and 4.62 (2d, 2, CIi2) , 4.35 (t, 3, OCIiZ (CItZ)6CH3) ) , 5.07
(s, 1, cH) , 7. 0-7.5 (m, e, Ar-II) .
Anal. Calcd. for C23II7804: C, 74.97; II, 7.66
Found: C, 74.6; H, 8.2



1V() 91/11011119 PC1~/tJS9f1/(?3672
-~- - 2 5 -
2 0 3 5 0 2 4 ~X~1MPL~ 9
n-Butoxvethyl l2ti-Dibe~zofd.ctl f ~., 3ldioxocin-~-~~xbo~~.z to
Crudel2H-d:ibenzo[d, g][1,3]dioxocin-6-carbonyl
chloride (4.8 g, 17.5 mmol.) is dissolved in toluene and
treated with a solution of 2-butoxyethanol (2.77 ml,
21 mmol) and 5 ml of triethylamine in toluene at 0°C
under argon. The mixture is heated at reflux for 2 hours
and then cooled to room temperature. The mixture is
poured into 150 ml of water and extracted with 4 x 100 ml
of ethyl acetate. 'fhe organic solution is washed with 5
percent hydrochloric acid, 5 percent sodium hydroxide and
then brine, dried with magnesium sulfate and filtered.
The solvent is removed to leave a yellow liquid which is
chrornatographed on dry column silica gel, using ethyl
ether/hexane ( 1: 2 ) as the solvent, to give a yellowish
oil (4.3 g, 69 percent). An analytically pure material
is obtained by using F~reap tlo.in layer chromatography. IR
(neat) 1770, 1582 cm's. Eli NMIZ (CDC1.3) 0.75-1.3 (m,
31i, Clip) , 1.2-2. 0 (m, 41f, CIIz) , 3. 3-4. 0 (m, 5N, OCHZ and
benzylic) , 4 .4-4.9 (m, 311, OCOCIIZ and benzylic) , 5. 6 (s,
1H, Cli) , 6.9-7.5 (m, 81i, aromatic) .
Anal. Ca~.cd. for CZ~Hz,~05: C, 70.7; H, 6.79
Found : C, 7 0 . 4 ; li , 6 . 9



1f() 91/IIUOtl9 I'Cf/1JS90/03672
X035024
,~- -26_
~XAj~]PLE 10
Cvclohexyl 12H-Dibenzord.qlLl,3~ dioxocin-6-carboxylate
Crudel2li-dibenzo[d,g][1,3]dioxocin-6-carbonyl
chloride (4 g, 14.5 mmol) is dissolved in 45 ml of
toluene and treated with cyelohexanol ( 1. 75 g, 17 . 5 mmol )
and 3 ml of triethylami.ne at 0°C under argon. The
mixture is heated at reflux for ?. hours, cooled, washed
with 5 percent sodium hydroxide then brine, dried with
magnesium sulfate and filtered. 'fhe solvent is removed
to leave a brown liquid which is chromatographed on dry
column silica gel, using ethyl ether/hexane as solvent,
to isolate a yellow :solid. This solid is ~aecolorized
with charcoal to give a off-wtrite solid (4.32 g, 87.7
percent) , mp 120-125'C: IR (KiSr) 1755, 1.580 cm~~. ~Ii
NMR (CUC13) 1.0-2.4 (m, 11II, cyclohexyl) , 3.37, 3.6,
4.51 and 4 .73 (q, 2I(, CIIZ) , 5.05 (s, III, UCIi) 6.9-7.45
(m, BIi, aromatic) .
Anal . Calcd. for CZ~Ii2z04: C, 74 . 54 ; II, 6. 55
Found: C, 74 . 3 ; ~i, 6 . 6
2 0 EXAMPLE 7.1
Tetrahydrofurfuryl 12II-Uibenzo[d,g][1,3]dioxocin-6-
carboxylate _
To a solution of crude l2li-dibenzo[d,g] [1,3]
dioxocin-6-carbonyl chloride (4.25 g, 15 mmol) in toluene
is slowly added a solution of tetrahydrofurfuryl alcohol



1f() 91/(100119
I'CT/US90/03C7Z
-27-
(. 8 ml, 18 mmol) and 7 ml of triethylamine in toluene at
U . under nitrogen. The mixture is heated at reflux for
1 hour, cooled and treated with water and ethyl acetate.
The organic layer is wa:~iied with 10 percent sodium
hydroxide then brine, dried with magnesium sulfate and
filtered. The solvent is removed leaving a yellowish oil
which is chromatograph nd on dry column silica gel using
ethyl acetate/hexane as the solvent. The resultant
(still yellow) oil i~~ decolorized with charcoal and
solidified to yield a white solid (4.12 g, 78 percent)
mp 83-85°C: IR (KF3r) 1760, 1580, cm-~, ~Ii NMR
(CDC13) 1.6-2.4 (m, 4Fi, CII?) , 3.35, 3.57, 4. 5 and 4.71
(q, 2H, CI(z) , 3.7-4. 1 (m, 2.Ii, CIIzO) , 4 . 1-4 . 5 (m, 31'i
OCHZCIIO) , 5. 1 (S, lII, CII) 6. 95-7.5 (m, BII, aromatic) .
Anal. Calcd. for CZONzoOS: C, 70.58; Ii, 5.9?.
Found: C, 70.8; II, 5.9
EXA1~PLE 12
Ethyl 12H-Dibenzofd c~l_L1~31dioxocin-6-thiocarboxylate
'fo a solution of l2li-dibenzv[d,g](1,3]dioxocin
-6-carboxylic acid (1 gram, 3.9 mmol) and ethanethiol
( 0 . 8 ml , 5 . 9 mmol ) in 10 ml of dry tetrahydrofuran at
-25'C, is added dicyclohexyl carboximide (DCC, 2 grams,
9.8 mmol) under argon. The mixture is stirred at -20'C
for 2 hours and then kept in ttoe refrigerator overnight.
The mixture is warmed to room temperature and to it is
added an aqueous solution of oxalic acid to destroy the
excess DCC. The mixture is diluted with ethyl ether and



1V() ~) I /(I(IUU9 ~ ~ (~ I'CI~/ l!S90/03(72
20 3
-28_
filtered. The solid is washed with ethylacetate and the
filtrate separated. 'fI-re organic layer is washed with to
percent sodium hydroxide and then with water twice and
brine once. The organic solution is next dried over
magnesium sulfate and filtered. The solvent is removed
to give a yellowish vi sCOUS oil which was clrromatographed
on dry column silica gel using ethyl acetate/Irexane (1:2)
as the solvent to give a yellowish viscous oil (890 mg).
This oil was solidified in petroleum ether to give a
white solid, mp 77.5-79°C: IR (KBr) 1690, 1000, 7580
cm~~; ~Ii PIMR (CDC13) 1.2-1.6 (t, 3Ii, CHI3) , 2.82-3.28
(q, 2Ii, SCFiZ) , 3.37, 3.58, 4.49 and 4.69 (q, 2Ii, Cliz) ,
4.99 (s, lFi, CHO) , 7.02-7.45 (m, 8H, aromatic) .
Anal. Calcd. for C»Ii~603S: C, 67.98; II, 5.37
Found : C, 67 . 8 ; 1i, 5 . 5
EXAM~'LE 12A
12H-Uibenzojd glfl 3ldioxocin-6-thivcarboxamide
A stirred solution of 12II-dibenzo(d,g)[1,3)
dioxocin-6-carboxamido (3.88 grams, 0.0152 mol) and
Lawesson's reagent (3.69 grams, 0.00912 mol) in 40 ml of
toluene is heated at rerlux. After 2.5 hours, the
reaction is cooled to room temperature and concentrated
under reduced pressure to afford a dark gummy residue.
Flash chromatography of this material (elution with
CHZClz) affords 1.6 grams of product as a tan solid.
Recrystallization from hexanes results in 1.1 grams of
product as an off white solid: mp. 165-169°C; IR (KBr)



wo ~mooooo t~crius~~oio3~>7z
2Q35024 -29-
3380, 3140, 1615, 1440, 1220, 975 cm's; 'H NMR
(DMSO-db) 3.65 and 4.41 (2d, 2, 12a and 12b), 5.17 (s,
1, Fib) , 7.0-7.6 (m, 8, Ar-FI) .
Anal. Calcd. for C~5Ii~3NOZS: C, 66.4; ii, 4.8; N, 5.2
Found: C, 66.5; FI, 4.9; N, 5.1
~;?CA1~~~ 13
12H-Dibenzofd,qlfl 3]d~ox_ocin~6-~ t i a
To a stirred solution of 12F1-dibenzo[d,g] [1,3]
dioxocin-f-carboxamide (8.24 grams, 0.0323 mol) and
pyridine (5.74 ml, 0.071 mol.) in 80 ml of 1,4-dioxane at
0°C, is added trifluoroacetic anhydride (5.0 ml, 0.0355
mol). After stirring for 5 minutes at 0'C, the reaction
is warmed to room temperature and stirred for 3 hours.
'The volatiles are removed under reduced pressure, the
residue taken up into ethyl acetate, washed with 1N NC1,
fiz0, saturated aqueous NaIIC03, brine, dried over MgS04
and c~onceratrated to afford G.8 grams of a white solid.
Recrystallization from cyclohexane affords 5.46 grams (71
percent) of product as a wtrite solid; mp 127-130'C; IR
(KBr) 6.28, 6.71, 6.85, 7.44, 8.1, 8.45, 8.96, 13.1 cm'r;
~H NMR (60 MIiz, CDC13) 3.83 and 4.29 (2d, 2, CHZ) ,
5.84 (s, 1, CFi) , 7.2-'7.0 (m, 8, Ar-FF) .
Anal. Calcd. for CrSFFrN02: C, 75.94; H, 4.07; N, 5.90
Found: C, 75.8; H, 4,0; N, 5.g



1V() 91/00(1(19
2 0 3 5 0 2 4 i~~ Iv ~59()/(»~,~2
-30-
~X_J1M P LE 14
Sodium 12H-Dibenzo(_d ct1f1~7~c~icxocin-6-c~rboxvlate
A solution of l2li-dibenzo[d,g][1,3)dioxocin-6-
carboxylic acid (1.3 grams, 0.00507 mol.) and NaOIi (0.41
grams, 0.0101 mol) in 50 ml of metloanol is refluxed for
30 minutes. The reaction mixture is then concentrated
under reduced pressure and the residue recrystallized
from ethanol-water to afford 0.65 grams (45 percent) of
product as a white solid: mp greater than 320°C; IR
(KBr) 3.0, 6.2, 7.0, 13.25, 8.35, 7Ø45, 13.3 cm-~; ~H NMR
(60 Mliz, Dz0) 3.3 and 4.4 (2d, 2~, Ctiz) , 4.8 (s, 1,
CIi) , 6.8-7. 4 (M, 8, Ar-Fi) .
Anal. Calcd. for C~SII~~U4Na 1/2 It20: C, 62.7; H, 4.2
Found: C, 63.0; N, 3.9
,~ X.AM E 15
Potassium 12H-Dibenzo_Ld,alI1.31~ioxocin-6-carboxylate
A mixture of 12II-dibenzo[d,g)[1,3]dioxocin-6-
carboxylic acid (5.0 g, 0.0195 mol) and potassium
carbonate (1.95 g, 0.0195 mol) in 100 ml of water is
stirred at room temperatture for 4 hours tlaen at 45 ° C for
2 hours . 'rhe reaction mixture is then cooled to room
temperature, treated with charcoal and concentrated to
afford a wet off-white solid. This material is
recrystallized from ethanol to give 2.27 g (39.5 percent)
of product as a white-gray solid: mp 275-290°C; IR (KBr)


fV() 9!/00(1(19 I'Cf/LJS90/()3C72
2035024
,r-- - 31. -
2730-3600, 1610, 980, 760 cm-~; ~Ii NMR (CDC1~) 3.5 and
4.35 (2d, ?., CHZ) , 4.5 (s, 1, Iib) , G.8-7.5 (m, 8, Ar-I;) .
Anal. Calcd. for C~SIi»04K~1/2 II20: C, 59.4 ; H, 3.99
Found: C, 59.2; II, 4.5
~XlIMPI.E 16
Diethanolamine Salt of 1211-Dibenzo[d,g)[1,3]dioxocin-6-
carboxylic Acid
To a stirred solution of 12H-dibenzo [ d, g] [ 1 , 3 ]
dioxocin-6-carboxylic acid (4.0 grams, 0.o15G mol) in 40
ml of tetrahydrofura» is added diethanolamine (1.64
grams, 0.0156 mol). after ?. hours at room temperature,
the solids that formed are collected by filtration,
washed with ether and dried to afford 5.04 grams (89
percent) of product as a white salad: mp 114-116'C; IR
(KBr) 3.0-4.0, 6.2.5, 6.'79, 7.05, 8.1, 10.35 cm-~; ~Ii NMR
(60 Mliz, DMSO-db) 3.05 (m, 4, (CIIzCIiZOIi)z) , 3.55 and
4.37 (2d, 2, CHZ) , 3.75 (m, 4, (CIIzCIIZOIi)Z) , 4.69 (s,
l,Cli) , 6.4-7.5 (m, 12, Ar-Ii and 4 exchangeable) .
Anal. Calcd. for C~9IIz306: C, 63.15; Ii, 6.41; N, 3.88
Found: C, G3.2; ti, 6.4; N, 4.0



1fU cll/(IIIUOc) I'CI~/L1S90/03G71
,._.. _ 3 2
~?~~l.Pla~. 17
2035024
12H-L7ibenzo[d,g][1,3]dioxocin-G-carboxylic acid dimethyl
amine salt
'to a solution of 1211-d.i.benzo[d,g][1,3]dioxocin
-6-carboxylic acid (5 g, 19.5 mmol) in ethyl
acetate/benzene is added excess liquid dimethylamine at
0 ° C under nitrogen. 'I'txe mixture i.s stirred overnight at
room temperature under nitrogen. The resultant solid is
filtered and dried to yield 5.5 g of white solid,
mp 164-172°C: IR (KF3r) 1640 cm-~; ~H NMR (CUC13) 2.51
(s, 6H, NCI(3) , 3.47, 3.6, 4.25, and 4.4 (q, 21i, CHZ) ,
4.55 (s, 111, CHCOZ) 6.8-7.5 (m, 81I, aromatic) .
Anal. Calcd, for C»1i~90,'N: C, 67.76; lI, 6.36; N, 4.65
Found: C, 67.7; II, 6.5; N, 5.0
EXAMPLE x8
4(2,2-Uimethyl-1,3-dioxolt~nyl)methyl 1211-dibenzo[d, g]
11.3] dioxocin-6-carbox_ylate
12H-Dibenzo[d,g][1,3]dioxocin-6-carbonyl
chloride (10 g, 39 mmol) is dissolved in toluene and
added to a solution of glycerolketal (5.6 ml, 45 mmol)
and l0 ml of triethylamine i.n toluene at 0-10'C under
argon. The mixture is heated at reflux for 5 hours,
cooled to room temperature, poured into 150 ml of water
and extracted with 4 x 1.50 ml of ethyl acetate. The
organic solution is washed with 5 percent IIC1, 5 percent



1VU 91/00(10'l I'Cf/US9U/(?3(72
3 ~ ~ ~ 4 -33-
NaOIi and then brine, dried with magnesium sulfate and
filtered. The soJ.vent is removed and the residue
chromatographed on dry column silica gel using ethyl
ether/hexane (1:1) as the solvent to give a yellowish
liquid which is crystallized in petroleum ether. The
solid is filtered and washed with petroleum ether to give
a white solid, mp 109-111°C: IR (KBr) 1780, 1581 cm-~,
III NMR (CDC13) 1.4 and 1.47 (2S, 6Ii, CH3) , 3. 36, 3.58,
4.49 and 4 .7 (q, 2II, CIIZ) , 3.7-4.4 (m, 3Ii, C1I0 and CHzO) ,
4.4-4. 6 (m, 2Fi, OCNZ) , 5.1 (s, 1H, OCIiO) , f . 95-7.45 (m,
BII, aromatic) .
Anal. Calcd. for CZ~IIzZ06: C, 68.10; Ii, 5.99
Found: C, 68.3; Ii, 6.0
EX11MPLE 19
t4ethyl-6-Methyl-l2li-Dibenzo[d,g)(1,3)dioxocin-6-
carboxvlate
To a stirred solution of isopropyl cyclohexyl
amrne (2.92 ml, 0.0178 mol) in 15 ml of dry
tetrahydrofuran (THF) under. N2 at 0°C is added n-BuLi
(11.84 ml of 1.5 M in hexane). After stirring 15 minutes
at 0 ° C, the solution is cooled to -65 ° C and a solution of
methyl l2li-dibenzo[d, g) (1,3)dioxocin-6-carboxylate
(4.G g, 0.0148 mol) in 10 ml of TIiF is added dropwise
over a period of 5 minutes. The solution is stirred at
-65°C for an additional 10 minutes and then added via
syringe over a period of 2 minutes to a solution of
methyl iodide (1.84 ml, 0.0246 mol) in 25 ml of dry



~5'() ~) I /(IOflf)9 ~ I'CT/ US90/03Fr72
2050
'"' -3d-
dimethyl sulfoxide rat room temperature. After stirring
for 30 minutes, the reaction mixture is diluted with
300 ml of Cli2Clz, washed with liz0, 1N FiCl and then brine,
dried over MgS04 and concentrated. The residue obtained
is purified by dry column chromatography (elution with
1:4 ethyl. acetate-hexanes) to afford 2 g of a yellow
syrup. This material was subjected to IiFLC purification
(Waters 500, 2 columns, 4 cycles, elution with 1:7
ethylacetate- hexanes) tU afford 1.1 g (2G percent) of
lU product as a clear syrup: IR (neat) 5.65, 6.3, 6.7,
6.85, 7.25 cm~~; ~Ii NMR (60 Mliz, CDC13) 1.36 (s, 3,
CII3) , 3.71 and 4.32 (2d, 2., CIIZ) 3.9 (s, 3, OCH3) ,
6.95-7.4 (m, 8, Ar-II) .
Anal. Calcd. for Cr~II»04: C, 71.82; H, 5.67
Found: C, 71.8; H, 5.7
EXAMPLE 20
(cis and trans) Methyl-12-Methyl-l2li-Dibenzo[d,g)(1,3]
dioxocin-6-carbox~late
A mixture of ?.,2'ethylidenebisphenol (10.0
grams, 0.0467 mol), d.ichl.oroacetic acid (3.85 ml, 0.0467
mol) and potassium carbonate (25.8 grams, 0.187 mol) in
200 ml of isopropyl alcohol is heated at reflux for 24
hours with vigorous stirring, after which an additional
3.85 ml of dichloroacetic acid is added and the mixture
refluxed with stirring for 70 hours. The isopropyl
alcohol is removed by distillation at atmospheric
pressure and replaced gradually with IiZO. The reaction



N'( ) 9 I /01111(19
2 0 3 5 0 2 4 i'~/us~o/o3«z
-35-
mixture is cooled, acidified by addition of concentrated
IiCl and extracted into chloroform. 'the chloroform
extract is washed with brine, treated with charcoal,
dried over MgS04 and concentrated to afford a
quantitative yield of crude acid. This material is then


converted to the methyl ester by refluxing in a methanol


solution ( 100 ml ) in the presence of conc . IiZS04 (
0 . 6 ml )


for 2 hours. The solution is cooled, 50 ml of CH2ClZ
is


added and th e mixture neutralized by tire addition of


solid NaZCO3. The inorganic salts are removed by


filtration a nd the filtrate concentrated and taken up


into CHZC12, washed with brine, dried over MgSO4 and


concentrated to afford 11.5 grams of a dark semi-solid.


Dry column chromatography
(elution with 1:4
EtOAc-hexane)


lp yields 5.0 gr ams (38 percent) of product as a white solid


consisting of a 1: 1 mixture of cis and traps isomers
: mp


95-120'C; IR (thin film) 5.62, 6.7, 6.9, 8.2, 9.25,


10.05, 13.05 cm~~; rl-I NMR (60 Mliz, CUC13) 1.66 and
1.89


(2d, 2, CH3) , 3.88 and 3.95 (2s, 3, OCIi3) , 3.95 and
5.1


(2q, 2, CH) , 5.0 and 5.36 (2s, 1, CIi) , 7.0-7.5 (m,
8,


Ar-H).


Anal. Calcd. for C»Hr604: C, 71.82; Ii, 5.67
Found: C, 71.6; Ii, 5.7
ethyl 12,12-Dimethyl-12~i-dibenzo[d,g][1,3]diaxocin-6-
carboxvlate
A mixture of ?.,2~-isopropylidene bisphenol
(3.65 g, 0.01594 mol), potassium hydroxide (2.68 g of 85



W o 91 /nuoov I'Cf/US9t1/03G72
2035024 --36-
percent, 0.0478 mol) and dichloroacetic acid (1.31 ml,
0.01594 mol) in 65 ml of isopropyl alcohol is heated at
reflex. After 20 hours at reflex, an additional 1.79 g
of 85 percent KOH and 1..31 ml. of di.chloroacetic acid are
added and the reaction mixture is heated at reflex for 2
days. The reaction mixture is then diluted with 200 ml
of HzO, acidified by the addition of concentrated FiCl
(10 ml) and extracted into ethyl acetate. The ethyl
acetate solution is washed with brine, dried over MgSO4
l0 and concentrated. The residue is washed with petroleum
ether to afford 3.7 g of crude product as a red-brown
syrup. This material is then purified by an
esterification-saponif.icati.on-esterification procedure
(esterification agent mettaanol, llZSO4) . Ury column
chromatography yield; 0.97 g of crude product, which is
saponified (NaOH, Meoli-1120) , and purified by dry column
chromatography to afford O.GO g of a white solid.
Esterification of this material (Et011, IIZS04) and
purification by preparative thin layer chromatography
(elution with 1:4 ethyl acetate-hexanes) yields 0.25 g of
product as a clear syrup: IR (neat) 3.34, 5.65, 6.95,
8.2, 13.2 crn-~; rIi NMR (CDC13) 1.28 (t, 3, CIIzCH3) , 1.75
and 1.9 (2s, 6, (CIi3)ZC) , 4.24 (q, 2, CHZCH3) , (s, 1,
CII) , 6.9-7. 6 (m, 8, Ar-Ii) ~ m/e 312.
Anal . Calcd. for C~911200,~: C, 73 . OG; Ii, 6, 45
Found: C, 72.4; Ii, 5.7



wo vtioouov ocriusvoio3o7z
-37-
~XI~MPLE ~ ~ 0 3 5 0 2 4
12H-Dibenzo[d,g)[1,3)dioxocin-12-hydroxy-6-carboxylic
acid Lactone
To a stirred sol.ut.ion of 12H-dibenzo [d, g] [ 1, 3 )
dioxocin-12-keto-6-carboxylic acid (10.U g, 0.0370 mol)
and sodium hydroxide (1.63 g, 0.0407 mol) in 200 ml of
5:3 ethanol-water is added sodium borohydride (1.40 g,
0. 0370 mol ) and the reaction is heated to 55 ° C. After 16
hours at 55 ° C, the reaction is cooled to r oom temperature
lU and poured cautiously onto 1 rlCl ( 500 ml ) , then extracted
with ethyl acetate. Z'tne ethyl acetate solution is washed
with brinE>., dried over MgS04 and concentrated to afford
a quantitative yield of a mixture of alcohols and
lactone. This mixture and p-toluenesulfonic acid
(O.US g) in 250 ml of benzene is heated at reflux. After
2 hours, the reaction is cooled to room temperature,
diluted with ethyl acetate and filtered to remove
insoluble polymeric material. The filtrate is washed
with saturated aqueous ldatrC03, then brine, dried over
MgSO4 and concentrated to afford 6.1 g (64 percent) of a
white solid (approximately 95 percent pure).
Analytically pure material is obtained by dry column
chromatography (eluti.on with 1:2 EtOAc-hexanes) , followed
by recrystallization from benzene-hexanes: mp 147-149°C;
IR (KF3r) 5.73, 6.74, 7.76, 8.41, 9.74, 13.36 cm't, tH NMR
(60 MriZ, CDC13) 5.97 (s, 7., CHC02-) , G.39 (s, 1,
ArZCI_r-O) , 6.8-7.4 (m, 8, Ar-N) .
Anal. Calcd. for Ct5Hto0': C, 70.86; r1, 3.96
Found: C, 71.2; Ir, 4.0



1~'() ~)I/I111U119 I'('1'/USc)(1/1)3G72
-3I1-
E_X.III~FLE 23
X035024
Ethyl 1-Methyl l2ti-dibenzo[d,g]~1,3)aioxocin-6-
carboxYlate
A mixture of 6-methyl-2 , 2' -methylene bisphenol
(3.1 g, 0.0145 mole), potassium hydroxide (2.87 g of 85
percent, 0.0434 mol) and dichloroacetic acid (1.2 ml,
0.0145 mol) in 55 ml of isopropyl alcohol is heated at
reflux. After 22 hours at reflux, an additional 1.91 g
of 85 percent KOH and 1.2 ml of dichloroacetic acid are
added and the reaction mixture is refluxed for 4 hours.
'fhe reaction mixture is then cooled, diluted with 150 ml
of Ii20, acidified by the addition of concentrated IiCl and
extracted into ethyl acetate. The ethyl acetate solution
is washed with brine, c:iried over MgS04 and concentrated
to afford the crude acid as a gummy yellow-tan solid. A
solution of the cruc:te acid and concentrated IizS04
(0.2 ml) in 25 ml of ethanol is heated at reflux.
After 2 hours, the solution is cooled to room
temperature , diluted w.i.th Cli?Cl.z ( 15 ml ) and neutral ized
by tire addition of solid NazC03. The inorganics are
removed by filtration and the filtrate is concentrated
under reduced pressure. Ttae residue obtained i.s taken up
into etluyl acetate, washed with IIzO, then brine, dried
over MgS04 and concentrated to afford 3.9 g of an amber
syrup. Dry column chromatography (elution with 1:4 ethyl
acetate-hexanes) followed by recrystallization from



~1'() 91/tltltltly 1'C1~/US')0/03C7Z
-3g- ~ 0 3 5 0 2 4
cyclohexane yields 1. () g of product as a white solid:
mp 78-83'C; IR (KE3r) 1759, 1205, 1065, 98U c:m-~; ~I1 NMR
(CDC13) 1.41 (t, 3, CII?~3) , 2.52 (s, 3, CIi3) , 3.69 and
4.45 (2d, 2, (AR)2-CIi?) , 4.4 (q, ?_, CIizCIl3) , 5.05 (s, 1,
CIi), 6.85-7.5 (m, 7, Ar-Ii); mass spectrum, m/e (M+) 298.
~~I1MPLE 24
Methyl 2-Methyl-12H-dibenzo[d,gJ[1,3)dioxocin-6-
carbox_y_late
into a 3-neck round bottom fl<zsk fitted with a
mechanical stirrer and a condenser, is placed 4-methyl
bis (1-hydroxy-2-phenyl)-methane (10.2 g, 48 mmol) and
potassium carbonate (26.33 g, 19U mmol.) in 200 ml of
isopropanol. Dichloroacetic acid (3.93 ml, 48 mmol) is
then added and the mixture is heated at reflex for 1 day.
More dichloroacetic acid (3.93 ml, 48 mmol) is added and
reflex is resumed for 3 more days. 400 ml of water is
then added arod the mixture is acidified with hydrochloric
acid. After stirring tire mixture for 2 hours at room
temperature and extracting with 200 ml of ethyl acetate
twice, the combined organic layer is next washed with 200
ml of 1M HCl and 150 ml of brine, dried with magnesium
sulfate and filtered. The solvent is removed, yielding
about 17 g of brown oil. This oil is used directly for
esterification. It is dissolved in 150 ml of methanol
and 0.3 ml of concentrated sulfuric acid is added. The
mixture is heated to reflex for 2 hours and then cooled
to room temperature. Sodium carbonate is added and the
mixture is stirred for ~ luour. Following filtration of


..., ~","wm I'C'I~/US90/U3G72
20~5Q24 -4"
the mixture, the solvent is removed and the crude solids
dissolved in methylene ctvloride, washed with 100 ml of 5
percent sodium hydroxide slid 150 ml of brine, dried with
MgSO~ and filtered. 'floe solvent is then removed to yield
about 7 g of brown solid, which is chromatographed on dry
column silica gel using ethyl ether/hexane as the solvent
to give about 5.5 g of wtoite solid. This solid was
re-crystallized in ethyl ettrer/hexane to give 4.51 g of
white solid. mp lUG-1U8.5'C. IR (KBr): 1761,
1748 cm~~. ~H NMR (CDC13) : 2.27 (s, iii, CH3) , 3.3, 3.5,
4.46 and 4 . 67 (q, 2H, CFI) , 3.92 (s, 3H, OCIi3) , 5.02 (s,
lli, CfiO) , 6. 85-7 . 5 (m, 7II aromatic H) .
Anal. Calcd. fox C~THi~6iiG: C, 71.82, H, 5.67
Found: C, 71.5; Ii, 5.7
~XI~M~LE 2~
3-Methyl-12-H-dibenzofd alf1~.31dioxocin-6-carboxylic acid
To a suspension of sodium hydride (5.7 g of a
50 percent dispersion in oil, washed with petroleum
ether; 0.1193 mol) and 18-crown-6 (0.45 g) in 65 ml of
1,4-dioxane is added slowly, dropwise, a solution of
dichloroacetic acid (4.0 ml, 0.049 mol) in 65 ml of
1,4-dioxane over a period of 15 minutes, followed by the
dropwise addition of 5-methyl-2,2'methylenebisphenol
(6.36 g, 0.0297 mol) in 85 ml of 1,4-dioxane over a
2 5 period of 4 5 minutes . The reaction mix is them heated at
about 90°C for 18 hours and then at reflux for 4 hours.
Next, it is cooled to room temperature, poured onto



~V() 91/()0(109 I'C.'f/llS9()/(?3672
2035024
-41-
600 ml of H2o, acidified by the addition of concentrated
HC1 and extracted with ethyl acetate (2 x 500 ml). The
ethyl acetate extract, is washed with brine, dried over
MgS04 and concentrated to afford 9.9 g of crude product
as a semi-solid. Purification via extraction with
cyclohexane in a Soxhlet apparatus yields 5.0 g (62.3
percent) of product as a white solid: mp 149-152'C; IR
(Ki3r) 1730, 1245, 122.0, 1015 cm~r; riI NMR (DMSO-d6) 2.2
(s, 3, CFi3) , 3.54 and 4.3 (2d, 2, htZa -+- Iir2b) , 5.01 (s,
1, 116) , 6.8-7.5 (m, 7, Ar-Ii) .
anal. Calcd. for C~611~404; C, 70.7; Ii, 5.3
Found: C, 71.1; Ii, 5.22
~X PLE 26
Methyl 4-methyl-12H-dibenzo[d,g)[1,3)dioxocin-6-
carboxvlate
n mixture of crude 6-methyl 2,2'-methylene
bisptrenol (7.0 g, 0.0327 mol), potassium hydroxide
(5.5 g, 0.098 mol) and dichloroacetic acid (2.7 ml,
0.037_7 mol) in 130 ml of-. isopropyl alcohol is heated at
reflux for 23 hours, following which an additional 5.5 g
of potassium hydroxide (0.098 mal) and tt-ren 2.7 ml of
dichloroacetic ac.i.d (0.0327 mol) are added and the
reaction mixture is again heated at reflux for an
additional 3 hours. 'fhe mixture is then cooled to room
temperature, diluted with 4U0 ml of water, acidified by
the addition of concentrated IIC1 (15 ml), extracted with
ethyl acetate (200 ml) and tine resultant organic solution



1V() 91/00009 I'('1'/US90/03~~72
2Q35024
"'° -42-
is washed with brine, dried over MgS04 and concentrated.
The residue is then co-evaporated with toluene to afford
g of crude acid as a tan solid. A solution of the
crude acid and concentrated IIzS04 (0.6 ml) in 100 ml of
5 methanol is heated at reflux for 2 hours, after which the
reaction mixture is cooled to room temperature, diluted
with 25 ml of CFi2C1 and neutralized by the addition of
solid NaZCO3. The inorganic salts are removed by
filtration and the filtrate concentrated under reduced
10 pressure. The residue is taken up into a mixture of
EtOAc-ether, washed wittn water, 5 percent aqueous NaOIi,
then brine, dried over. MgSO4 and concentrated to afford
7.0 g of a yellow syrup. Ury column chromatography
(elution with 1:4 EtOAc-toexanes) afforded 4.1 g (44
percent) of product as a white solid; greater than 95
percent purity. Recrystallization from cycloh exane
afforded 2.1 g (23 percent) of pure product: mp
107-109?; IR (KBr) 5.74, f.97, f3.3, 9.5, 10.2, 13.5 cm's;
rIi NMR (90 MHz, CDC13) , 2.23 (s, 3, CIi3) , 3.41 (d, 1,
Ii-CH) , 3.95 (s, 3, OCII3) , 4.62 (d, 1, fi C-Ii) , 5.04 (s, 1,
OCH_O), 6.9-7.4 (m, 7, Ar-Ii).
Anal. Calcd. for C»II~604: C, 71.(32; II, 5.67
Found: C, 71. Q; Ii, 5.6
~CI1M_pLE 27
2-Methoxyethyl l2li-Dibenzo[d,gJ[1,3)dioxocin-6-
carboxylate
l2li-Dibenzo[d,gJ(l,3Jdioxocin-6-carbonyl
chloride (5.33 g, 19.5 mmol) is dissolved in toluene and



wo m/uoo°v I>CI~/usv0/(13~~72
20 3 5 0 2 4 -43-
added to a solution of 2-methoxyethanol (2.2 ml,
27.6 mmol) and 7 ml of triethylamine in toluene at
0 ° -10 ° C under argon. The mixture is heated at reflux for
3 hours, cooled to roam temperature, poured into 150 ml
of water and extracted witty 4 x 100 ml of ethyl acetate.
The resultant organic solution is washed with 5 percent
hydrochloric acid, 5 percent sodium hydroxide and brine,
dried with magnesium sulfate and filtered. The solvent
is removed to give a brownish solid which is
chromatographed on dry column silica gel, using ethyl
ether/hexane (1:1) as the solvent, to give a yellowish
oil. This oil is solidified, th a solid is filtered and
washed with ethyl ether/hexaroe to yield a white solid:
mp 74-76°C: IR (KBr) 1779, 1581 cm~~; ~Ii NMR
(CDC13) 3.42 (s, 31i, CF13) , 3.3-4. 0 (m, 3H, CIi and
OCIiz) , 4.35-4.8 (m, 3Ii, CIi and OCIi2) , 5. 1 (s, 1H, OCHO) ,
6.9-7.45 (m, 8H, aromatic).
Anal. Calcd. for C~olIy805: C, 68.78; 11, 5.7'7
Found: C, 69.1; Fi, 5.9
EXAMPLE 28
2-Ethylhexy112H-Dibetyzo I d , c~ ~ ~ ~. , 3 ] dioxocin-6-carboxylate
To a stirred solution of 12H-dibenzo[d, g]
dioxocin-6-carbonyl chloride (4 g, 0.015 mol) in 45 ml of
toluene is added a solution of 2-ethylhexanol (2.28 g,
2.5 0 . 017 mol ) and 4 ml of trietlrylamine in toluene at 0' C
under argon. The mixture is heated at reflux for 2
hours, cooled, washed with 5 percent Na0lI and then brine,
dried with magnesium sulfate and filtered. The solvent



~1'() 91/(1011(19 I'('I~/US9(1/03G72
2035024
-44-
is removed to give a brown liquid which is
chromatographed on dry column silica gel using ethyl
ether/hexane as the solvent to yield a yellowish oil
(4.5 g) : IH (neat) 1770, 1500 cm's. ~Ii NMR (CDC13)
0.5-2.0 (m, 15H, CtIZ and Cli3) , 3.33, 3.53, 4.48, and 4.68
(q, 2H, CHZ) , 4.15-4. 35 (d, 211, OCFIz) , 5.2 (s, 1H, CH) ,
6.9-7.4 (m, 8H, aromatic).
Anal . Calcd. for CZ3112$O4: C, 74 . 97; F1, 7 , 66
Found: C, 75.1, ti, 7.9
EXAMPLE 29
Ethyl 3-t-~3uty1-l2Hi-dibenzo [d, g] [ 1, 3 ]dioxocin-6-
carboxylate
A mixture of 4-t-butyl-2, 2' -mettrylene bisphenol
(3.67 g, 0.0143 mol), potassium hydroxide (2.84 g of 85
percent, 0.0429 mol.) acrd di.chloroacetic acid (1.18 ml,
0.0143 mol) in 55 ml of isopropyl alcohol is heated at
reflux. After 17 hours at reflux, an additional 1.90 g
of 85 percent KOIi and 1.18 ml of dichloroacet.ic acid is
added and reflux is continued for 4 hours. Thereafter,
the reaction mixture is cooled to room temperature,
diluted with 150 ml of 1120, acidified by tire addition of
concentrated HiCl and extracted into ethyl acetate. The
ethyl acetate solution i.s washed with brine, dried over
MgS04 and concentrated to afford crude acid as a
yellow-brown syrup. A solution of the crude acid and
p-toluene sulfonic acid (U.07 g) in 25 ml of 10:1
C1iC13-ethanol is heated at reflux for 1.5 hours with
azetropic removal of water. TOe solution is then cooled


1fU ') I /t10t1(Iy fCI-/US9U/03672
205024 -45-
to room temperature, diluted with 50 ml of CIiCl3,
washed


with HZO, 5 percent aqueous NaOIi a:ad then brine, dried


over MgS04, and concentrated to afford 3.93 g of
a


yellow-brown syrup. Dry column chromatography (elution


with 1:4 EtOAc-hexanes) yields 2.4 g (49 percent)
of


product as a cloudy syrup: IR (neat) 2975, 1770, 1755,


1485, 1410, 1260, 76 em-~ f ~I1 NMR (CDC13) 1.24 (s,
9,


C(CIi3)3) , 1.43 (t, 3, CIIZC~3) , 3.43 and 4.51
( 2d, 2


11RZCIiz) , 4 . 39 (q, 2, CIIZCIi3) , 5. 05 (s, 7.0-7.4 (m,
1 CIi) ,


7, Ar-II) ; mass spectrum, m/e (M-H) 340, (M+ - CH3) 323,


(M+ - CH3CIIzOH) 294, (M+ - C4119) 283, (M+ - COZEt) 267.


~XhMPLE 30
Ethyl3-Trifluorometlryl-l2tl-dibenzo [d, g ] [ 1., 3 ] dioxocin-6-
carboxylate
To a suspension of sodium hydride (2.55 g of a
50 percent dispersion in oil, washed with petroleum
ether., 0.0531 mol) amd 18-crown-6 (0.?. g) in 30 ml of
1,4-dioxane is slowly added dropwise, a solution of
dichloroacetic acid (1.81 ML, 0.0219 mol) in 30 ml of
1,4-dioxane over a period of 15 minutes, followed by the
dropwise addition of 5-trifluoromethyl-2,2~-methylene
bisphenol (3.56 g, 0.0133 mol) in 40 ml of. 1,4-dioxane
over a period of 45 minutes. The reaction is then heated
at reflux for 20 I-yours, cooled to room temperature,
poured into 300 ml of HzO, acidified by the addition of
concentrated IiCl, amd extracted with ethyl acetate
(2 x 200 ml). The ethyl acetate extract is washed with
brine, dried over MgS04 alld concentrated to afford an



wc) viiooao~~ t~c'riusooio3o~z
205024
-4 6-
oily residue which i ~ .further washed with petroleum ether
to give 4.6 g of an orange-yellow semi-solid. A solution
of this material and p-toluene sulfonic acid (0.07 g) in
30 ml of 10:1 CHC13-ethanol is heated at reflux for 1
hour with azetropic removal of water. The solution is
then cooled to room temperature, diluted with 50 ml of
CHC13, washed with Ii2U, 5 percent aqueous Na0li, and then
brine, dried over MgS04, and concentrated to afford
3.75 g of a dark residue. Flash chromatography of this
material (elution with 1:6 ethyl acetate-hexanes) affords
1.91 g (41 percent) of product as a white solid:
mp 78-81°C; IR (KBr) 1765, 1325, 1115, 990 cm's; ~Fi NMR
(C()C13) 1.41 (t, 3, CHzCII3) , 3.52 and 4.51 (2 d, 2,
H~Za, Ii~Zb) , 4.41 (q, 2, CEi2C113) , 5.09 (s, 1, H6) , 7.0-7.5
(m, 7, Ar-fi) .
Anal. Calcd. for C~etl~SF304: C, 61.37; H, 4.29
Found: C, 61.41 H, 4.2
~XA LE 31
Methyl 4,8-Dimethyl 17.H-dibenzo[d,g][1,3]dioxocin-6-
2o carboxylate _
A mixture of 2,2'-methylene bis-6-methyl phenol
(4.0 g, 0.0175 mol), dichloroacetic acid (1.45 ml,
0.0175 mol) and potassium carbonate (9.7 g, 0.070 mol) in
100 ml of isopropyl alcohol is heated at reflux for
24 hours with vigorous stirring after which an additional
1.45 ml of dichloroacetic acid is added and the mixture
refluxed with stirring for 70 trours. The isopropyl
alcohol is removed by distillation at atmospheric



1VU ~) i /(lU(l0y I'Cl'/ US90/03G72
X035024
-47-
pressure and replaced gradually with IizO. The mixture is
cooled to 0°C and the solids collected by filtration.
Water (75 m) is added to ttoe solids and the mixture made
strongly acidic with concentrated IiCl. The mixture is
extracted into CIizClz, washed with brine, dried over
MgS04 and concentrated to afford 3.0 g (73 percent) of
the carboxylic acid. Esterification (methanol, FiZSO4,
reflux) followed by dry column chromatography (elution
with 1:4 ethyl acetate- hexanes), affords 1.9 g (50
percent) of product as a white solid: mp 134-135°C; IR
(KBr) 5.65, 6.72, a.2, 13.1 cm~~; ~Ii NMR (60 Mliz,
CDC13) 2.21 (s, 6, 7 CH3) , 3.3F3 and 4. G2 (2d, 2, CHZ) ,
4.0 (s, 3, CH3) , 4.99 (s, 1, CIi) , 6.9-7.3 (m, 6, Ar-H) .
Anal. Calcd. for Creiirn04.1/4 Ii20: C, 71.4; H, G.16
Found: C, 71.2; II, 6.1
XII~P~E 3 2
Methyl 4,a-Dichloro l2Fi-dj_benzo[d,g][1,3]dioxocin-6-
carboxYlate
A mixture of 2 , 2' -rnethylene bis-6-chlorophenol
7.0 (10.0 g, 0.0372 mol), diclrloroacetic acid (3.07 ml,
0.0372 mol) and potassium carbonate (20.6 g, 0.149 mol)
in 150 ml of isopropyl alcohol is heated at reflux for 24
hours with vigorous stirring after which an additional
3.07 ml of dichloroacetic acid is added and the mixture
refluxed with stirring for 67 hours. The isopropyl
alcohol is removed by distillation at atmospheric
pressure and replaced with water, gradually. The
reaction mixture is cooled, acidified by addition of



~V() 91/UOIIU9 I'CT/US90/03G72
2p35p24
-4Ei-
concentrated HC1 and extracted with CIiCl3. The
chloroform extract is washed with brine, treated with
charcoal, dried over MgS04 and concentrated to afford
12.39 of crude carboxylic acid. Esterification
(methanol, IizS04, reflux) followed by dry column
chromatography (elution with 1:4 ethyl acetate-hexanes)
affords 5.29 g of product as a white solid:
mp 114-116°C; IR (KBr) 5.65, 6.95, 8.29, 9.47, 10.3 cm's:
~H NMR (60 MHz, CDC13) 3.4? and 4.67 (2d, 2, Cliz) , 3.99
(s, 3, CH3), 5.04 (s, 1, CII), 6.9-7.3 (8, m, Ar-H).
Anal. Calcd. for C~6II~zClz04: C, 56.66; Ii, 3.57
Found: C, 56.7; II, 3.5
EXAMPLE 33
3,9-Dimethyl-12H-dibertzo[d,g][1,3]dioxocin-G-carboxylic
acid
A mixture of 2 , 2' -methylenebis ( 5-methylphenol )
(8.3 g, 0.0364 mol), dichloroacetic acid (3.0 ml,
0.0364 mol) and potassium carbonate (20.1 g, 0.145 mol)
in 220 ml of isopropyl alcohol is heated at reflux for
24 hours with vigorous stirring after which an additional
3.0 ml (0.0364 mol) of dichloroacetic acid is added and
the mixture is refluxed for an additional 72 hours. The
isopropyl alcohol is distilled off and replaced with
water. The reaction mixture is then cooled to room
temperature and aci_di.fi.ed by the addition of concentrated
HC1 (35 ml). The solids that form are collected by
filtration, taken up into ethyl acetate and the ethyl
acetate solution is washed with 1N IIC1, then brine, dried



v~o mnnonv ncrius~uio:~c,~2
X035024
over MgS04 and concentrated to afford a quantitative
yield of crude product as n tan solid. Extraction of the
crude product with hot cyclohexane in a Soxhlet
extraction apparatus results in 4.55 g (44 percent) of
product as a white solid from the cooled cyclohexane
solution. Recrystallization from benzene-hexanes yields
an analytically pure material: mp 172-174'C; IR (KBr)
3.4, 5.8, 8.0, 8.9 cm's; III tJMR (60 MHz, DMSO-db) 2.21
(s, 6, 2 CH3) , 3.52 (d, 1, II-C-Ii) 4.23 (d, 1, H-C-H) ,
6.8-7.4 (6, m, Ar-H).
Anal. Calcd. for C»I-I~oo4: C, 71.82; Ii, 5.67
Fot.rnd: C, 72.1; ~H, 5.7
~XN~ E 3 4
Methyl 3,9-Dimethoxy-J.2II-dibenzo[d,g][1,3]dioxocin-6-
carboxylate
'to a solution of_- potassium hydroxide (1.29 g,
23 mmol) in 100 ml of isopropanol is added 1, 1'-methylene
bis(4-methoxy-2-phenol) (1.8 g, 6.9 mmol) and then,
O. G ml of dichloroacet.i.c acid (7.2 mmol) . The mixture is
heated at reflux overnight. The mixture is then cooled
to room temperature and potassium hydroxide (1.29 g,
23 mmol) and dichloroacetic acid (0.6 ml, 7.2 mmol) are
added. The mixture is again refluxed overnight. The
solvent is removed on n rotavap and water is added. The
mixture is then acidified with concentrated hydrochloric
acid and extracted with ethyl acetate three times. The
organic layer is washed with brine, dried with magnesium



1V() 91 /UQOiI'l I'CfI tJS90/03C72
-5°- 2035024
sulfate and filtered. The solvent is removed, leaving a
yellow oil. This oil is dissolved in 30 ml of methanol
and 1 ml of boron trifltroride etherate is added. The
mixture is next stirred at room temperature for 4 hours,
poured into saturated aqueous sodium chloride ( 50 ml ) and
extracted with ethyl acetate three times. The resulting
organic solution is washed with 5 percent sodium
hydroxide (50 ml) and brine, dried with magnesium sulfate
and filtered. The solvent is removed to leave a yellow
l0 oil which is chromatographed on a dry column silica gel
using ethyl acetate/hexane (2:1) as the solvent to give
a white solid (1.16 g), mp 102-106'C: IR (YI3r) 1750,
1620, 1505 cm -~. ~Hi NMR (CDC13) 3.25, 3.4, 4.31 and
4.45 (q, 2Ii, Cliz) , 367 (s, GII, OCIi3) , 3.9?. (s, 3Ii, OCIi3) ,
5.06 (s, 2Ii, OCH) , 6. 5-7.25 (m, 6Ii, aromatic) .
Anal. Calcd. for C~8H~e06: C, 65.45; Ii, 5.49
Found: C, 65.2; Ii, 5.5
EXAMPLE 35
Methyl 4-t-Butyl-1211-dibenzo[d,g][1,3)dioxocin-6-
carboxylate
To a suspension of sodium hydride (1.65 g of a
50 percent dispersion in oil, washed with petroleum
ether, 0.0343 mol) and 18-crown-6 (0.13 g) in 16 ml of
1,4-dioxane is added slowly, dr~pwise, a solution of
dichloroacetic acid (1.17 ml, 0.0142 mol) in 18 ml of
1,4-dioxane over a period of 15 minutes followed by the
dropwise addition of 6-t-butyl-2,2'-methylene bisphenol



1V(> 91/11(1009 i'CI~/LJS90/03C,72
°°' - 51-
2035024
(2.2g, 0. 00858 mol) in 21 ml of 1, 4-dioxane over a period
of 25 minutes. The reaction mixture is then heated at
reflux. lifter 24 hours at reflux, the reaction mixture
is cooled to room temperature, poured into 150 ml of lizo,
acidified by the addition of concentrated HCl (10 ml) and
extracted with ethyl acetate (2 x 100 ml). The extract
is washed with brine, dried over MgS04 and concentrated
to afford crude carboxylic acid as a yellow-brown syrupy
residue. This material is taken up into ether (15 ml)
and treated with excess ethereal diazomethane (about
0.6 g in 30 ml of ether). After standing overnight at
room temperature, the reaction mixture i.s evaporated and
the residue purified by dry column chromatography
(elution with 1:4 EtOAC-hexanes) to afford 0.66 g of
slightly impure product. Preparative TLC (elution with
1:10 ether: petroleum ether) yields 0.44 g (16 percent)
of pure product as an off white solid: mp 113-117°C; IR
(KBr) 2950, 1760, 1205, 970 cm-~; ~1i NMR (CUC13) 1.3
(s, 9, (CIi3)3C) , 3.42 and 4.6 (2d, 2, C1IZ) , 3.94 (s, 3,
COOCII3), 5.05 (s, 1, CH), 6.97-7.4 (m, 7, Ar-H).
Anal. Calcd. for CZOiizz04: C, 73.6; Ii, 6.79
Found: C, 73.5; N, 7.0
~l~MPLE 3 6
4-Methyl-1211-dibenzo[d,g][1,3]dioxocin-6-carboxylic acid,
diethanolamine salt
A solution of 4-methyl-12H-dibenzo[d, g)[1,3]
dioxocin-6-carboxylic acid (0.64 g, 0.00237 mol) and



~VU 91/00009 I'Cf/US90/03f72
w...
2 0 ~ 5 0 2 4 -52-
diethanolamine (0.25 g, 0.00237 mol) in 6.4 ml of TFiF is
stirred at room temperature. After 18 hours, the clear
solution is concentrated under reduced pressure and the
residue stirred for 1 hour with 15 ml of ether. The
ether is then decanted away, leaving a clear syrup which
is dried under vacuum to a.ffard 0.88 g (99 percent) of a
white hygroscopic cryst~alli.ne foam: IR (thirn film) 3.0,
6.15, 8.12, 10.32; ~Ii NMR (CDC13) 2.2.1 (s, 3, CH3) ,
:F . 1-3 . 5 (m, 5, 2 CIiZ and (Ar. ) z-C-~I) , 3 . 8-4 . 2 (m, 4 , 2
lU CIIZ) , 4.45 (d, 1, (Ar)z-C-~) , 4.8 (s, 1, CII) , 6.8-7.4 (m,
7, Ar-Ii) .
EXAMPLE 37
N-Phen_Yl= l2Fi-dibenzofd,a1 f 1~ 3ldivxocin-6-carboxamide
To a stirred solution of crude 12H-
dibenzo[d,g][1,3]dioxocin-6-carboxylicacid chloride(4.3
g, 0.016 mol) and triethylamine (3.3 ml, 0.24 mol) in 40
ml of toluene was added dropwise a solution of aniline
(1.6 ml, 0.017 mol) in 10 ml of toluene over a period of
5 minutes. After being stirred 4.5 h at RT, the reaction
was filtered to remove the insolubles that formed. the
filtrate was concentrated under reduced pressure. The
residue obtained was purified by dry column
chromatogr,phy (elution with 1:2 ethyl acetat-hexanes) to
afford 3.2 g of product. Recrystallization from ethyl
acetate-hexanes gave 1.8 g (35%) of product as a white
solid: mp 164-165:0; IR (ICI3r) 6.0, 6.79, 6.97, 8.28,
10.35, 13.27m; ~H NMR (60 MIIz, CUC13) 3.45 and 4.55 (2d,
2, CHz) , 5. 07 (s, l, CII) , 7.0-8. B (m, 8, Ar-Ii) , 8.6 (b,
l, NII) .



1f() 91/(111()09 I'CT/US9(1/03C72
205024
_53_
Anal. Calcd. for CZ~II»03N: C, 76.1; Ii, 5.2: N, 4.2.
C, 76.0; It, 5.3; N, 4.3
EX71MPLE 3838
1-Aza-12H-Dibenzo[d.ct]j113]dioxocin-G-carboxylic acid
To a suspension of sodium hydride (4.93 g of a
50% dispersion in oil which was washed with petroleum
ether, 0.1 mol) and 18-crown-6 (0.39 g) in 55 ml of 1,4-
dioxane was added dropwise a solution of dichloroacetic
acid (3.5 ml, 0.04 mol) in 55 ml of 1,4-dioxane of a
period of 15 min. followed by the dropwise addition of 3-
hydrosy-2-(2'-hydroxybenzyl)pyridine (5.17 g, 0.026 mol)
in 75 ml of 1,4-di.oxane of a period of 40 minutes. The
reaction was then heated at reflux. After 24 h at reflux
the reaction was cooled to room temperature, poured onto
500 ml of IizO, cautiously neutralized by the addition of
1H IiCl and extracted wi.tii ethyl acetate ( 3 x 500 ml ) .
The ehtyl acetate extract was washed with brine, dried
over MqSO~ and concentrated to afford the crude
carboxylic acid as a yellow-brown solid.
Recrystallization from methanol gave 1.5 g (23~) of pure
product as an off white solid; mp 224-227:C (d) ; IR (KF3r)
1748, 1440, 1225, 9'75 cm-~; IIi NMR (DMSO-d6) D=d3.8 and
4. 55 (2d, 2, Ii~zA arid 11f2~) , 5.2 (s, 1, 116) , 7.0-7.5 (m,
6, Ii3, I(4, Iie, H9, Ii~o, II~~) , 8.2 (m, 1, Hi2) .
Anal. Calcd. for C~~II»N04. s IiZO: C, 63.15, Ii, 4.5; H, 5.3
C, 63.0; I-i, 4.2; H, 5.0



wo ~~ i iuuuuy t~criusyoio~~~7z
2Q35024
'~ -54-
~li~.~ES 39 THROUGH 97
Additional examples of compounds that fall
within the scope of the present invention are described
in Table A. These were prepared by procedures analogous
to those given in the preceding examples.



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1V() 91 /(1110()9 !'f-'1'/L ~~'W~tt3G72
-58-
2035024
Pre and Post Emergent iie~bic~.dal Activity
The herbicide screening test is designed to
identify compounds that exhib3.t pre-emergence (Pre)
and/or post-emergence (Post) herbicidal activity.
Plantings of the indicated test species are seeded in
separate fiber pans (E3" X 10" X 3" deep) containing
pasteurized soil. Tfae POSt pans are seeded two weeks
prior to treatment. 'fhe I're pans are seeded one day
prior to application of the test compounds. One Pre and
one Post pan is employed for each compound, unless
otherwise indicated. Prior to application of the test
formulation, the Pre pans are mist watered to stabilize
the soil surface. The standard laboratory formulation at
the 8 kg/ha treatment rate is prepared by weighing
73.6 mg of the test compound into a 125 ml flask to which
is then added 40 ml of acetone followed by 4U ml of 0.1%
Ortho X-77 surfactant. If the test compound appears
insoluble in the formulation, it is treated for 1-2
minutes with an ultrasonic probe. If still insoluble,
the particle size is reduced by grinding to a size
sufficient to allow it to pass through the spray nozzle.
Following preparation of the test formulations, each is
then sprayed equally and completely on the Pre and Post
pans employing a handheld spray gun with an air atomizing
nozzle. Acetone is employed to rinse the spray gun
between application of each formulation. Tine treated
pans are then moved to a growth room, or greenhouse,
where they are maintained and appropriately watered for
13 days following treatment. At this time, the pans are



ivo ~munocw rc-rw~s~oio~f,~z
2 Q 3 5 0 Z ~"59-
then evaluated to determine the percent kill/inhibition/
suppression relative to an untreated control. The rating
numbers range from 0, indicating no injury, to 100,
indicating complete kill or control. Compounds that show
80~ control Post and 50~ control Pre against any 3
species are considered for further testing. Results are
shown in the following Table.



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-69- 20 3 5 0 2 4
T'he followi.rag examples and tables illustrate
some of the plant growth regulation activities of the
glyoxylate compositions of the present invention.
FXE 99
Effect on 'Turf Growth
The acid form of the glyoxylate prepared in
Example 1 was evaluated as a turf growth retardant on
four grass species at varying rates as indicated in
Table 2.
l0 Turf species were planted in 8 by a cm fiber
pots using steam pasteurized soil, and allowed to grow
until well established, i.e., roots extended to the
bottom of the fiber pot. The turf was clipped
periodically to keep the thatch at a manageable level and
fertilizer was applied on a regular basis. Prior to
application of the compound to the turf, the grass was
cut to vne cm. The compound was formulated in 15 X 125
mm disposable test tubes and f~liar applications were
made in a hood using a UeVilbliss Model EGA-502 hand held
sprayer.
height measurements were taken two weeks after
application of the compound, with the results set forth
in Table 2.
..



W() 91/OU009 I'C1'/US90/03G72
,.~.. _ 7 0 _
TAFiLE 2
2035024
IIEIQHT* (
cm)


RATE
kg/ha FEBTUCA POA FEBTUCA LOLIUM
ARUNDINACEA PRATENf3I8 RUBRA PERENE


0.1 5 5.5 4 4


0.5 3 3.5 3 2.5


1.0 2.5 3.5 3 2.5


2.0 2 1.5 3 2


4.0 1 1 2 1.5


Check 6 7 4 4.5


* Average of two replications
Despite some phytotoxicity~observed with this
method of application, good retardant effect, especially
on Kentucky Bluegrass, was demonstrated.
E~ChMPLE 100
Effect of Application Method vn Turf Retardancy
Using the turf species set forth and grown as
in Example 99, the effect of the method of application of
the compounds of Examples 1G and 2 is evaluated, with
results set forth in 'fable 3. Weight measurements are
taken by cutting eac:li turf pot, after two weeks, to a
uniform height, combining the clippings from all species
and oven drying prior to weighing.


1fU 91 /()11()09
,,- _ 71 _
I'CT/ US90/03G72
TALE 3
2035024
RATE LRY WEIGHT* g/ha)
CoMP (k


OUZID kg/ha
FOLIAR BAIL GRANULAR
DRENCH


Example 16 0.25 1.78 2.26 1.58


0.50 1.11 2.25 1.08


1.0 0.75 1.06 1.10


2.0 0.55 0.65 0.52


Av. 1.05 1.55 1.07


Example 2 0.25 1.10 1.51 2.44



0.50 1.45 U.83 2.48


1.0 1.12 0.72 2.10


2.0 1,2p 0.32 2.03


Av. 1.21 0.84 2.26


Check -- 2.49 2.49 2.49


* Average of two repl~.cations
Granular application is found to result in the
lowest degree of phytotoxicity to the grass species.
l0 EXAMPLE 101
Growth Regulation of Wheat
Wheat testing is done in 13 cm round plastic
pots. The wheat is planted in a mixture of 75 percent
soil and 25 percent sand which has been steam pasteurized
to control indigenous weed seed and pathogens . Seeds are
planted and then covered with approximately 1 cm
soil/sand mix and placed on fiber matting in the



W'()')1/0110(19 I'CI~/US90/03G7Z
-~2- 205024
greenhouse. The pots are both mist watered and bottom
watered until seedlings emerged. After emergence, only
bottom watering is done. At the times of treatment, the
growth stage is recoi:ded, and pots are removed to a spray
hood for treatment. Ttre compound to be applied is placed
in a 15 by 125 mm test tube and dissolved in 12 ml of
acetone and water. '.t'he compound is sprayed onto the
foliage using a hand held Devilbiss spray gun (Model
EGA-502). This sprayer emits an extremely fine spray
particle and results in maximum coverage of the foliage.
Operating air pressure is 840 gm/cm2. Applications are
made at four different rates at each of six growth
stages. The growth stages are as follows:
I. one leaf
II. three to four leaf, some initial tillering
III. three to tour leaf, distinct tillers with two
to three leaves
IV. five to six leaf, with four to five tillers
V. flag leaf present, inflorescence within culm
VI. boot stage, inflorescence emerging from culm
Results (being an average of all indicated
readings) for the compounds of Examples 1 and 16 are set
forth in Tables 4 and 5, respectively.



v~o vlioo°°v ncivusvoio3~~7z
~p;~~024-73-
TABLE 4
EFFECT ON GRAIN WI;IGI~TJ, WEIGHT
INTERNODE LENGT i AND BREI~KING STRENGTH
GRAIN PLANT LENGTlI LENGTH BREAICING
5TREATMENT WEIGHT HEIGHT am cm STRENGTH
kg/ha gm cm INTERNODE INTERNODE gm
A B


0 0.62 28.3 24.8 8.6 61.0


2 0.61 31.7 19.9 7.1 66.7


4 0.53 31.5 20.0 7.0 53.9


* Weight necessary to break a 10 cm segment of Internode A.
TABLE 5
EFFECT ON i~UriBER OF TILI~)~R:3 PRO UCING GR71IN. GRAIN WEIGIiT
STRAW WEIGHT hND P~N'I' IiEIGiiT
GRAIN STRAW PLANT
RATE TILLER WEIGIiT WEIGHT HEIGHT
kg/ha COUNT gm gm cm


0 16.2 12.1 13.4 23.3


1/2 18.1 12.6 14.7 23.7


1 19.0 12.8 15.2 22.5


2 19.7 1.3.7 15.8 22.9


4 19.2 13.1 15.0 22.9


Effect on Wheat Tillerinct
Single soft red winter wheat (Triticum
aestivum) seedlings growing in soil in 4 inch R plastic



wo ~moono~~ rcriusooin3~,~2
2035024
pots are treated with broadcast spray applications of the
compound of Example 15. 11t the tune of treatment, the
plants are starting to tiller. Most seedlings have one
tiller, while a few have two or no tillers. Treatments
are repl icated six times ( except 5 times at 3 gm/ha ) . At
various times during the course of the study, various
parameters are determined: number of flag leaves, number
of seed heads and yield measurements. These and other
determinations are reported in Table 6. No commercial
l0 standard is included, because none is known. The yield
increases are attributed to increased tillering (flag
leaf counts) and therefore more seed heads per plant.
The high dosage (1,000 gm/1)a tends to delay tillering.
TADLE 6
-- -_ -
Doaope N~wlwcr Total GrainSced
Nubcr Seed p~ Lft.
ANha Flsp (% of control)
leaves/Plent Nenda/Plant ~g/Seed
-


3 6.4 ~ 10,4 10.2 t 27.1 (136)30.4
1.5 t 3.5 4.1


10 6.0 : 8,3 t 8.2 t 2.2 20.7 (104)29.2
1.3 3.1


30 9.0 t 11.7 11.8 t 28.9 (145)28.2
2.4 t 2.7 3.7


2 0 100 7.5 s 13.7 14.0 t 33.5 (168)27.7
1.5 t 2.1 1.7


300 6.0 : 13.3 13.5 t 33.9 (170)28.5
1.4 t 3.3 4.4


1000 3.7 : 15.3 14.T t 35.0 (176)27.9
3.1 ~ 2.6 3.3


Control5.8 s 8.0 ~ 7.3 t 3.4 iD.9 (100)27,0
2.5 3.B


DAT1 57 96 145 (harvest)162 162


2 5 ~ DAT = Deys After Treatment
NOTE: Grain uas pooled for each treatment erd weighed 17 days after harvest
(162 DAT).
The 3 gm/ho treatment was ed)usted to 6 replicates.



W() 91/0(1()09 1'CT/US90/03G72
''~ -75-
~X71MPLE 1. 0 3
~f ect on Weed Beets 2 0 3 5 0 2 4
In some areas where sugar beets ( eta vulaaris)
are grown, many fields become infested with weed beets
which do not form usable roots. These weed beets can
also bolt any time during the season thus insuring
continuing infestations. No herbicide is selective
enough to control weed beets in sugar beets. A possible
weed beet management approach would be to prevent seed
production by early treatment of flower stalks with
wipe-on or recirculating sprayer applications. To this
end, three greenhouse studies are attempted and reported
in Table 7. Test plants are grown in 5" R plastic pots.
Treatments are applied as directed sprays onto developing
flower stalks. Percent reduction is based on fresh
weight of surviving floral growth. The compound from
Example 1 is prepared as an acetone/water/ surfactant lab
formulation. ROUNDUPTN (Monsanto) and A-RESTT" (Eli
Lilly) are commercial herbicide and plant growth regulant
formulations, respectively.



W() 91/0000') I'Cf/US9(1/03Cr72
-76-
235024
TnHZ.$ ~
Percent Reduction
of Floral
Parts


Dosage
Compound mg/Plant Test n Test H Test C


Example 1 0.1 1G 100 100


0.3 35 100 100


09 100 100 100


Roundup" 2.0 (5G)Z 3g ___


6.0 11 gg ___


18.0 100 100 --_


71-RestT~ 0.33 --- --- 21


1.0 ___ '___ 69


3.0 __- __- 92


DATA 28 63 32


DAT = Days After Treatment
Denotes percent increase
&~~ 104
Effect on Maple Seed~i a s
Actively glowing seedlings of cer palmatum.
(Japanese cutleaf maple) are sprayed to runoff with
aqueous dilutions of the compound of Example 15 and
ATRINAL~~ (a commercial formulation by MAAG of
dikegulac). Pinched as well as untreated controls are
included. All treatments (4 replicates each, recorded 78
days after treatment) are listed in Table 8.



~V() 91/(IU(1(I~1 PCT/US90/03G72
_77-
203~~24
Glyoxylate dosages bracket the range from no
effect to an excessive effect at the dosages tested.
TA>3LE 8
compound Concentration Hean Number
(pPm) Terminals/Plant


Example 15 5 1.0 0.0


15 58 2.2


50 9.5 3.0


150 9.8 2.4


500 greater than 14


Artrinal 1500 11.5 2.5


3000 9.0 0.8


Control - ---- 1.0 0.0


Pinched Control ---- 1.3 1.5~


' Two of the four seedlings went dormant after pinching.
l0
EXAMPLE 1n~
effect on Azaleas
Rooted single-stem cuttings of azaleas
(Rhododendron sp., cv 'Elsi Lee') are transplanted to
artificial potting medium in 4 inch round plastic pots.
These cuttings are pinched as they were moved. After
growth resumes, these plants are sprayed to run-off using
a hand held spray unit. Treatments employ the K salt of
Example 15 and dikegulac, a commercial plant growth
regulator which is used to induce branching and to


1V0 91 /(10(109
~Q~~~24 '7a-
~'C1~/US9()/03G72
prevent regrowth after pruning. Treatments, based on
five replicates of each are listed in Table 9.
Flower bud counts are recorded 122 days after
treatment. Glyoxylate treatments induced increases in
flower bud numbers.
TABLE 9
-- -~ _
~ concentration Mean Number
'


C
om ound ~Ppm) Flower nuds/plants


Example 15 10 3.2 1.9


20 8.4 3.1


40 15.8 4.3


80 23.2 5.8


1G0 Partial


defoliation,


Stunted


l0 Dikegulac 1500


5.2 3.5


3000 5.4 2.7


6000 5.2 3.7


Control


---- 3.0 0.7


Pinched Control*


---- 7.2 2.4


* All plants are pinched when potted. The "pinched
control" is pinched a second time, when the other plants
are sprayed.




_7g_
Effect On Brs~m~hW ci of Cleans 2~, 3 5 0 2 4
In order to determine their effect on branching
patterns in plants, compounds were evaluated on
Charlevoix ~ limbing beans. Under normal conditions,
these plants exhibit strong apical dominance with little
or no branching. Plants were grown individually in 4"
diameter pots in the greenhouse, and were treated when
the lst trifoliate leaf was expanded (plants
l0 approximately 10" tall). Two independent studies were
conducted. In the first, compounds were applied at 25
ppm, while in the second the application rate was
increased to 100 ppm. In both studies, compounds were
sprayed on plants to runoff using a hand-held sprayer.
Compounds were dissolved in a solvent system of 67% water
and 3 3 % acetone with 0 . 067 % (v/v ) Tween 2 0 added as a
surfactant. For some compounds not soluble in this
system, 100% acetone with Tween 20 was used. For each
compound, three replicate plants were treated and
evaluated. Plants were grown in the greenhouse for an
additional 3 weeks before the compounds' activity was
evaluated. Results are summarized in Table 10.



1V() ~) 1 /1101)09 I'Ct~/t1S90/03672
-00-
TADLE 10
EFFECT OF COMPOUNDS (DE~~GNATED ~~~AMpLE NUL~BER) ON
NC NG C G W EATM NT
Rating Code: 0 = No effect
l = Slight effect a~ txxf break
2 = Moderate effect a~ bud break aril branching ~ ~ 3 5 n
3 = Strong enhoncement of bud break and brerxhin ;J ~/g
Exnple Rate Ncd~ Exa~rte Rate hear,


Rstinp t Rating
25 L00 25 l00 !


1 3 3 3.0 27 3 3 3.0


2 3 3 3.0 28 1 3 2.0


3 2 3 2.5 29 0 1 0.5


5 2 3 2.5 30 0 1 0.5


b 2 3 2.5 31 0 1 0.5


7 1 2 1.5 32 i -- 1.0 _


1 3 2.0 33 2 1 1.5


9 3 1 2.0 ~ 1 1 1.0


10 3 3 3.0 35 2 0 1.0


11 3 3 3.0 3b 1 3 2.0


2 12 1 3 2.0' 38 2 1 1.5
0


12~ 3 3 3.0 39 2 3 2.5


13 1 3 2.0 40 t 2 1.5


14 2 3 2.5 41 3 3 3.0


15 3 3 3.0 42 3 3 3.0


2 16 1 3 2.0 43 2 1 1.5
5


17 3 3 3.0 44 2 1 1.5


18 3 3 3.0 45 2 1 1.5


19 0 1 0.5 46 1 1 1.0


0 1 0.5 47 2 1 1.5


21 1 2 1.5 4B 2 i 1.5


22 2 1 1.5 49 2 3 2.5


24 1 1 1.0 50 2 1 1.5


26 1 3 2.0 52 2 1 1.5





1V() 91 /0(1009
~~~5~24 -°1~
I'C1~/US90/03G72
- ~.~.
E~~'Pi~ Rete Ncen Exwe~~ie R


ete
Retinp Rating
_ l00
~


53 Z 1. 5 75 2 1 t . 5


54 1 1 t.0 76
t t 1.0


55 1 1 1.0 T7 2 1 1.5


56 1 1 1. U T8 _ 3 3 3 . 0


57 t 1 1.0 79 3 3 3.0


58 2 0 1.U 81 2 , 1.5


59 2 0 1.0 82 Z t t.5


60 t 1 1.0 83 0 1 0.5


61 1 1 1.0 83
0 t 0.5


62 1 1 1.0 85 1 0 0.5


63 1 3 2.0 ~ 0 t 0.5


t 3 2.0 87 t 0.5
65 3 3 3.0 88 0 1 0.5


t 3 2.0 89 0 1 0.5
67 1 3 2.0 ~ t 0.5
1 1.5 91 1 0 0.5
69 3 1 2.0 92 0 1 0.5
70 2 2 2.0
2 93 3 3 3.0
0 71 1 2 1.5
94 0 t 0.5
72 t 1 t.o 95 o t o.s
3 1 2.0 96 t 0.5


74 2 3 2.5 97 1 3 2.0


All of the compounds ellicited some degree of
increased bud break and/or branching in climbing beans.
For most compounds, activity tended to be greater at 100
ppm titan at 25 ppm. In summary, these compounds are
effective as branching enhancement agents in beans.



W() 91/(1(1(1(19 1'CI~/US90/()3G72
-82-
~XI,MPLE 107
Fffect vn Size Maintenance o~ ~~vet liedae ~ 0 3 5 0 2 4
Ten compounds were evaluated to determine their
efficacy in size maintenance of privet hedge. Potted
privet plants were overwintered in a protective cool
greenhouse and transferred to a warm greenhouse in early
March. Bud break and leaf development were allowed to
continue for 1 month until plant height was approximately
30 cm. Because privet hedge plants are commonly trimmed
to a desired shape, one-half of the plants were trimmed
prior to chemical application. Plants were sprayed to
runoff using a hand-toeld sprayer. Compounds were applied
at a concentration of 20 ppm in a solvent system of 50%
water, and 50% acetone containing 0.1% (v/v) Triton X-100
as a surfactant. For each treatment, ?. replicate trimmed
plants and 2 replicate non-trimmed plants were treated.
Plant height of each plant was recorded on the day of
treatment and compared to the plant height at 29 days
after treatment. Table 11 shows the net increase in
plant height after treatment.



~VU 91/(I(I(IU9 1'Cl~/US90/03(71
-83-
TABLE il
EFFECT OF CO~?OUNDS O~ HEIGHT CIiJI.NG~]~' OF 2 0 3 5 0 2 4
GOLDEN POET 29 DAyS AFTER TREATMENT
Net change in
Examplo ~ plant height
~cm~


Trimmed* Non-Trimmed**
Plants Plants


Non-Sprayed Control f3.0 7.0


Sprayed Control 7.0 7.5


1 0.0 -0.5


2 -2.5 -1.5


3 1.5 0.5


9 -1.0
-1.0


-0.5 0.0


41 -1.0 -2.0


42 0.0 2.0


65 -1.0 0.0


15 78 0.5
0.0


79 -0.5 0.0


*Average plant height at time of treatment was 30 cm.
**Average plant height at time of treatment was 40 cm.
Trimmed and non-trimmed plants responded
similarly to application of the compounds. Control
plants (both non-sprayed and those sprayed with the
solvent) grew from 7 to r3.5 cm. In contrast, plant
height remained essentially the same in all plants
treated with the compounds. Thus, these compounds were
quite effective in maintain~.ng plant size both in trimmed
and non-trimmed privet hedge plants.



1V() 91/II(I(II19 I'CT/hS90/03C72
-84-
Effect on Terminal Elos at on ~f Green Ash ~ ~ 3 5 0 2 4
Ten compounds were applied to green ash
seedlings to determine if they could control elongation
of terminal buds. Potted green ash seedlings were
overwintered in a cool greenhouse and transferred to a
warm greenhouse in early March. Wittrin 1 month terminal
buds were released and began to grow. Plants were then
sprayed to runoff using a hand-held sprayer. Compounds
1.0 were applied at two concentrations, 20 ppm arod 100 ppm,
in a solvent system of 50% water, 50% acetone containing
0.1% (v/v) Triton X-100 as a surfactant. For each
treatment, 4 replicate plants were treated. Plant height
of each plant was recorded on the day of treatment and
compared to the plant height at 2a days after treatment.
Table 12 shows the net increase in plant height after
treatment.

~
V() 91 /11111)09
I'C1'/US9(1/03G72
-~5- 20 3 5 0 2 4
TABLE 12
EFFECT OF COMPOUNDS ON IIEIGJIT CJiI~NGE OF GREEN ASH
SEEDLINGS 28 DAYS AFT'FI~ TREA'~rg'ENT
Net change in
Example ~ plant height*


(cm)


2o ppm loo ppm


Non-Sprayed 18.3


Control Pinched -


Non-Sprayed 11.0


Control Non-pinched


Sprayed Control 15
0


Pinched . ---


Sparyed Control 8.5


__
Non-Pinched


1 0.0 _
-0.3



2 -0.3
0.8


3
1
5


. -0.3



0.0
-1.5



15 0.8
0.0


17 0.0
-0.1


41 1.3
0.8


42
1
3


. 0.3


65 0. 5
-0.5


79 0.3
1.5


*Average plant height at time of treatment was 34 cm.
Non-sprayed control plants in which the
terminal bud was pinched grew 18.3 cm while non-sprayed
non-pinched plants grew 11 cm. Similarly, pinched
control plants sprayed with the solvent increased in




- 2035024
height 15 cm and non-pinched, non-sprayed plants grew 8.5
cm. In contrast, all compounds tested essentially
eliminated terminal bud elongation, regardless of
concentration of the applied solution. Thus, these
compounds appear to have excellent utility when used to
reduce vertical growth of this tree species.
Twenty-three compounds were tested for their
l0 utility as turfgrass retardants. Bluegrass, cv Haron and
perennial ryegrass, cv Pennfine were planted in 3" sqaure
pots in late February. Grass was allowed to grow for 6
weeks before treatment. Grass was cut and fertilized on -
a regular basis to provide a thick turf. Just prior to
chemical treatment, the bluegrass and ryegrass were
trimmed to heights of 20 mm and 15 mm, respectively.
Four replicate pots of each species were treated at two
rates, 0.5 kg/ha and 2.0 kg/ha. Compounds were sprayed
in 50% acetone, 50% water containing Triton X-100 at 0.1%
(v/v) as a surfactant. Some compounds were sprayed in
100% acetone containing Triton X-100 Plant heights 2
weeks after treatment were recorded and are summarized in
Table 13.



W<) 91/00(109 I'Cl'/US90/03G72
_F37~
203502 4
TAIILE 13
EFFECT OF COI~POUNUS O~I, P~.~11NT i;EIGHT OF BLUEGRASS AND
RYEGRASS ~g U~yS AFTER TREATMENT'
Plant ight
He (a~)


E s(~9ras s" R rasa r"
l


xa~ 0.5 2.0 0.5 2.0
e ! kg/ha kp/ha kg/ha kg~he


Non-5 ra ed Control 137.5 .__ 126.3 ---


S rayed Control 132.5 --- 130.0 ---


Embark 30.3 30.3 50.5 49.8


Limit (2.5 qt/acre) 43.5 --- 53.0 ---


I 44.3 40.8 31.8 26.3


1 0 2 49.8 40.5 27.5 26.8


3 39.0 _34.0 33.8 33.3


5 44.0 32.0 30.3 29.0


8 51.3 31.8 ZT.O 30.8


41.3 34.3 30.3 27.8


1 5 10 43.0 34.5 32.3 34.3


11 41.0 38.5 34.8 29.8


33.8 34.8 25.8 26.8


16 47.0 44.0 29.0 29.3


17 39.0 31.8 28.3 27.8


2 0 18 42.8 44.8 28.3 28.3


27 42.8 31.0 3D.5 24.3


36 95.0 81.8 40.5 42.0


39 67.5 44,3 34.8 32.8


41 48.8 39.8 43.8 34.5


2 5 42 117.5 106.3 101.3 85.0


65 47.8 45.8 33.3 32.8


68.3 _51.5 58.8 38.8


74 35.0 33.3 35.3 32.0






-ee-
2035024
Il~nt
Nel
t (v)


lluepr~s~ It rw"


Example 1
0.5 2.0 0.5 2.0
k1/hs k1/h~ k1/h~ k9/h~
i


33.fi 33.0 36.0 33.ls


T9 45.1! 52.5 G0.0 45.8


93 34.0 33.0 it.3 31.0


~Averspe plsnt height et time of trestment ws~ 20 ~.
~~Averspe plant height et tine o! treet~nent wse 15 urn.
Both bluegrass and ryegrass controls grew to a
total height of approximately 130 mm (net growth of 115
mmj during the two week preiod after treatment. The
commercial standards, Limit~ and Embark~ reduced total
l0 plant height to approximately 30 to 50 mm, depending upon
rate and species. Similar plant height reductions were _
observed in many of the compounds tested. Several
compounds, however, showed little or no activity. In
addition, responses also varied between the two species,
with ryegrass growth appearing to be more susceptible to
chemical retardation, particularly at low rates. In
summary, turf retardant activity of this class of
chemistry appears to be at least comparable to the
currently available commercial standards.
.B

Representative Drawing