Phosphoroamide urease inhibitors and urease inhibited urea based fertilizer compositions

Novel urease inhibiting phosphoroamide compounds and urea based fertilizer compositions including such compounds, and methods and compositions for inhibiting the activity of urease through use of a urease inhibiting effective amount of one or more of the aforementioned phosphoroamide compounds.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
This invention relates to phosphoroamide urease inhibitors and urease 
inhibited urea based fertilizer compositions. More particularly, this 
invention relates to urease inhibited urea based fertilizer compositions 
which contain certain phosphoroamide compounds as the urease inhibitors, 
and to methods of and compositions for inhibiting the catalytic activity 
of urease through application of such compounds to plant growth media. 
2. The Prior Art 
It is well known in the art to use urea and urea compositions in 
fertilizers, for application to the soil. The effective life of such 
fertilizers, however, is of short duration wherever microbiological 
activity exists in the soil to which the fertilizer is applied. This is 
due to the fact that urea is hydrolyzed rapidly, and nitrogen is lost in 
the form of ammonia, when urea is placed under or on the surface of soil 
which contains urease. Urease, a crystallizable enzyme occurring in 
numerous bacteria and fungi, as for example Micrococcus urease, catalyzes 
the conversion of urea into ammonia and carbon dioxide. The reactions are 
as follows: 
##STR1## 
A portion of the ammonia thus formed is held by absorbing constituents of 
the soil and is available to plants as nutrient. However, a large amount 
of the ammonia may be lost to the air. A further problem resulting from 
the action of urease is the accumulation of ammonium in the soil which may 
damage germinating seedlings and young plants. 
One approach to the reduction of the problems resulting from the activity 
of soil urease toward soil applied urea is to find compounds that inhibit 
urease activity when applied to soils in conjunction with fertilizer urea. 
This approach has received considerable attention, and several classes of 
compounds have been used as urease inhibitors. 
For example some prior art describes various phosphoro compounds which are 
useful as urease inhibitors. Illustrative of such prior art are East 
German Pat. Nos. 142,714, 212,026, 122,177, 122,621 and 130,936 and Great 
Britain Pat. No. 1,494,774 describe various phosphorodiamidate compounds 
as urease inhibitors. U.S. Pat. No. 4,242,325 describes a method of 
controlling the enzymatic decomposition of urea to ammonia and carbonic 
acid due to the action of urease which comprises exposing the enzyme to 
certain phosphoric triamide compounds. U.S. Pat. No. 4,182,881 describes 
the use of certain N-(diaminophosphinyl)arylcarboxyamide compounds as 
inhibitors of the enzyme urease in the urinary tract. U.S. Pat. No. 
4,225,526 describes the use of 
8-([(4-aminophenyl)sulfonyl])amino-2-napthalenyl phosphorodiamidate 
compounds as inhibitors of the enzyme urease, and U.S. Pat. No. 4,222,948 
describes the use of ([(4-aminophenyl)sulfonyl]amino])phenyl 
phosphorodimidates as inhibitors of the enzyme urease. 
Still other prior art describes the use of certain phosphoric triamide 
compounds for other purposes. For example, Great Britain Pat. No. 830,800 
describes certain phosphoric triamide compounds which are useful as 
flameproofing agents. U.S. Pat. Nos. 3,767,733 and 3,812,033 describe the 
use of substituted benzo(1',3',2')-dioxaphospholes derived from 
o-dihydroxybenzenes as lubricant additives. 
SUMMARY OF THE INVENTION 
In accordance with the present invention, there is provided a unique 
fertilizer composition comprising urea or a urea precursor compound which 
is capable of forming urea when subjected to the use conditions of the 
composition and a "urease inhibiting effective amount" of one or more 
phosphoroamide compounds of the formula: 
##STR2## 
wherein: 
R.sub.1 and R.sub.2 are the same or different and are hydrogen or alkyl 
having from 1 to about 4 carbon atoms; 
R.sub.3 is oxygen or sulfur; and 
X, Y or Z are the same or different and are hydrogen, alkyl, arylamino, 
diarylamino, halogen, hydroxy, mercapto, alkylmercapto, amino, cyano, 
nitro, alkylamino, dialkylamino, arylmercapto, isocyano, isocyanato, 
trihalogenmethyl, alkoxy, thiocyano, alkanoyl, diaminophosphinyl, 
O-diaminophosphinyl, S-diaminophosphinyl, N-diaminophosphinyl, or any two 
X, Y and Z groups together may form an alkylene or alkenylene chain which 
may optionally include one or more divalent oxygen, nitrogen, or sulfur 
moieties forming a 3,4,5 or 6 membered fused ring structure. In the 
present specification and claims, the term "phosphoroamide compounds" is 
used to refer to the above referenced compounds. 
Another aspect of this invention relates to a method of enhancing the yield 
and/or growth of plants by distributing the composition of this invention 
to the "plant growth media" in which the plants are being grown within 
reach of the root system of the plants (hereinafter referred to as "root 
zone"). As used herein, the term "plant growth media" refers to the 
various natural and artificial media which support plant growth, including 
but not limited to soil, potting mixtures of organic and inorganic matter, 
and artificial media such as polyurethane foam. 
Yet another aspect of this invention relates to a method of inhibiting the 
urease catalyzed hydrolysis of urea at some situs, as for example in a 
plant growth media, which method comprises applying a "urease inhibiting 
effective amount" of one or more of the above-mentioned phosphoroamide 
compounds to the plant growth media or other situs prior to, after or in 
conjunction with the application of urea and/or one or more compounds 
capable of forming urea in situ to said plant growth media or other situs. 
Still another aspect of this invention relates to a composition comprising 
a "urease inhibiting effective amount" of one or more of such 
phosphoroamide compounds useful for carrying out such method. As used 
herein, a "urease inhibiting effective amount" is an amount of such 
phosphoroamide compounds which when applied to a plant growth media or 
other situs is capable of inhibiting the urease catalyzed hydrolysis of 
urea applied to said media or said situs to any extent. 
It has been discovered that by distributing a urease inhibiting effective 
amount of one or more of the aforementioned phosphoroamide compounds in 
the said plant growth media, the urease catalyzed hydrolysis of urea to 
ammonia is suppressed, thereby retarding the rate at which urea is lost 
from the media. Furthermore, by proper distribution of the one or more 
phosphoroamide compounds in the plant growth media, this action of 
inhibiting the hydrolysis of urea to ammonia is effective over a prolonged 
period of time. 
DETAILED DESCRIPTION OF THE INVENTION 
The application of a urease inhibiting effective amount of one or more of 
the above-identified phosphoroamide compounds to some situs, as for 
example a plant growth media is essential for the practice of this 
invention. While the above described phosphoroamide compounds can be used 
to inhibit urease catalyzed hydrolysis in many different situs, they are 
preferred for use in inhibiting the activity of urease in a plant growth 
media. When used in the preferred embodiments of the invention, usually, 
at least about 0.01 parts of said one or more phosphoroamide compounds per 
million parts of said plant growth media will be applied to the plant 
growth media. Hereinafter the abbreviation "p.p.m." will be used to refer 
to parts by weight of one or more phosphoroamide compounds per one million 
parts by weight of plant growth media. In the preferred embodiments of 
this invention, the amount of said one or more phosphoroamide compounds 
distributed in said plant growth media is from about 0.01 to about 5000 
p.p.m., and in the particularly preferred embodiments is from about 0.2 to 
about 1000 p.p.m. Amongst these particularly preferred embodiments, most 
preferred are those embodiments in which the amount of said one or more 
phosphoroamide compounds distributed in said plant growth media is from 
about 1 to about 500 p.p.m. 
Within the above referenced limits, the particular amounts of one or more 
phosphoroamide compounds used are dependent upon the particular situation. 
Thus, in determining the amount to be employed, consideration is made not 
only of the treatment need, i.e., soil pH, temperature, soil type, etc., 
but also of the mode of application to soil. When the one or more 
phosphoroamide compounds is to be applied in a broadcast application, the 
amount in p.p.m. may frequently be less than in row or band applications 
where, for a substantial depth and width within the vicinity of 
application, there can be a very high concentration of the one or more 
phosphoroamide compounds. When application is made near the root zone of 
growing plants, or when application is made immediately prior to seeding 
or transplanting, the amounts supplied are frequently at a lower rate than 
when application is made at the end of the growing season to prepare the 
soil for the following season. By dispersing very large dosages in growth 
media, a prolonged inhibition of the activity of urease can be obtained 
over a period of many months. The concentration of the active one or more 
phosphoroamide compounds is eventually reduced to a minimum by 
decomposition in the soil or other plant growth media. 
In one method for carrying out the present invention, the one or more 
phosphoroamide compounds are distributed throughout the growth media in a 
broadcast application such as by spraying, dusting, distributing in 
irrigation water, and the like. In such application, the one or more 
phosphoroamide compounds are supplied in amounts sufficient to permeate 
the growing area of the plant growth media with a urease inhibiting 
effective amount of such compounds. In field administration, the one or 
more phosphoroamide compounds can be distributed in the plant growth media 
in an amount and through such cross-section of the plant growth media as 
to provide for the presence therein of a urease inhibiting effective 
amount of such compounds. It is usually preferred that the one or more 
phosphoroamide compounds be distributed below the surface of the plant 
growth media. 
In another method for carrying out the present invention, the one or more 
phosphoroamide compounds are administered to the plant growth media in a 
band or row application. In such application, administration is made with 
or without one or more carriers in amounts sufficient to supply to the 
soil or other plant growth media a urease inhibiting effective amount of 
the one or more phosphoroamide compounds. After administration with or 
without discing or dragging, subsequent irrigation or rainfall distributes 
the one or more phosphoroamide compounds throughout the plant growth 
media. 
In one embodiment of the present invention, the one or more phosphoroamide 
compounds is distributed throughout the plant growth media prior to 
seeding or transplanting the desired crop plant. 
In another embodiment, the soil in the root zone of growing plants is 
treated with the one or more phosphoroamide compounds in an amount 
effective to inhibit the activity of urease, but sublethal to plant 
growth. By following such practice, no adverse effect is exerted by the 
one or more phosphoroamide compounds upon growth of seeds or plants. 
Oftentimes, it is desirable to treat the soil or plant growth media 
adjacent to plants, and this procedure may be carried out conveniently in 
side-dressing operations. 
In a further embodiment, soil or other plant growth media can be treated 
with a urease inhibiting effective amount of phosphoroamide compounds 
following harvest to prevent rapid loss of urea. Such practice conserves 
the soil nitrogen for the following growing season. In such application, 
the upper limit is primarily an economic consideration. 
The present invention can be carried out by distributing the one or more 
phosphoroamide compounds in an unmodified form throughout the plant growth 
media. The present method also embraces distributing one or more such 
compounds as a constituent in liquid or finely divided solid urease 
inhibiting compositions. 
The concentration of one or more phosphoroamide compounds in compositions 
to be employed for the treatment of plant growth media is not critical and 
can vary considerably provided a urease inhibiting effective amount is 
supplied to the plant growth media. In general, good results are obtained 
with liquid and solid compositions containing at least about 0.00001 
percent by weight of the one or more phosphoroamide compounds based on the 
total weight of the compositions. In the preferred embodiments of the 
invention, the weight percent of one or more phosphoroamide compounds 
contained in said composition is from about 0.00001 to about 98 percent or 
more on the aforementioned basis, and in the particularly preferred 
embodiments is from about 0.001 to about 50 weight percent also on the 
aforementioned basis. Amongst these particularly preferred embodiments, 
most preferred are those embodiments in which the weight percent of said 
compounds contained in said composition is from about 0.002 to about 20, 
and ideally from about 0.01 to about 10. Liquid or solid compositions in 
which the one or more phosphoroamide compounds are present in higher 
concentration can be utilized as such or can be employed as concentrate 
compositions to be diluted to prepare actual treating compositions. 
In the composition of this invention, the one or more phosphoroamide 
compounds can be modified with one or more additaments or soil treating 
adjuvants including water, petroleum distillates or other liquid carriers, 
surface-active dispersing agents, inert finely divided solids and 
fertilizers, such as urea or one or more compounds capable of forming urea 
in situ. These adjuvants cooperate with the one or more phosphoroamide 
compounds so as to facilitate the practice of the present invention and to 
obtain an improved result. Preferred adjuvants are surface-active 
dispersing agents, inert finely divided solids, and various plant micro- 
and macro-nutrients, especially urea and/or urea precursor compounds 
capable of forming urea in situ. Urea is a well known, commercially 
available compound and will not be discussed herein in detail. 
Illustrative of compounds which are believed to form urea on addition to a 
plant growth media and which are water soluble are formaldehyde 
condensation products, as for example, methylolureas, methyleneureas and 
mixtures thereof. These products and a method for their preparation are 
described in detail in U.S. Pat. No. 3,462,256. Still other useful sources 
of urea are water-insoluble urea formaldehyde condensation products such 
as ureaform. Illustrative of useful water-insoluble urea and formaldehyde 
condensation products are those whose preparation and use are described in 
detail in U.S. Pat. Nos. 3,677,736 and 4,033,745. 
The amount of urea or urea precursor compound included in the composition 
of this invention is not critical to the unique advantages thereof, and 
any amount of urea and/or the urea precursor compound used in conventional 
fertilizers can be used in the conduct of this invention. Normally, the 
amount employed will vary widely depending on a number of factors, 
including the times and frequency of application. In the preferred 
embodiments of the invention, the quantity of urea or urea precursor 
compound may vary from about 0.5 to about 95 weight percent based on the 
total weight of the composition and in the particularly preferred 
embodiments may vary from about 1 to about 50 weight percent on the same 
basis. In the most preferred embodiments of this invention, the quantity 
of urea or urea precursor compound will vary from about 3 to about 40 
weight percent on the aforementioned basis. 
The composition of this invention preferably includes other optional 
ingredients known to those of skill in the art for inclusion in fertilizer 
compositions. For example, the composition may include sources of 
potassium, sulfur, phosphorus, boron, zinc, iron, manganese, copper, 
molybdenum, cobalt and like micronutrient and macronutrients which may be 
deficient in the soil. The composition may also include plant growth 
regulators, as for example auxins, cytokinins and the like, as well as 
pesticides, such as insecticides, miticides, herbicides, nematocides and 
the like. 
Liquid compositions containing the desired amount of one or more 
phosphoroamide compounds and other optional ingredients can be prepared by 
dispersing the latter in one or more liquid carriers, such as water or an 
organic solvent with or without the aid of a suitable surface active 
dispersing agent or emulsifying agent. Suitable organic solvents include 
acetone, diisobutylketone, methanol, ethanol, isopropyl alcohol, diethyl 
ether, toluene, methylene chloride, chlorobenzene and petroleum 
distillates. The preferred organic solvents are those which are of such 
volatility that they leave little permanent residue in the growth media. 
Dispersing and emulsifying agents which can be employed in liquid 
compositions include non-ionic, anionic, amphoteric and cationic 
dispersing agents, such as condensation products of alkylene oxides with 
phenols and organic acids, alkyl aryl sulfonates, polyoxyalkylene 
derivatives of sorbitol esters, sugar esters, complex ether alcohols, 
mahogany soaps, quaternary ammonium compounds and the like. The surface 
active agents are generally employed in the amount of from about 1 to 
about 20 percent by weight of the composition. 
Solid compositions containing the active one or more phosphoroamide 
compounds and other optional ingredients can be prepared by dispersing the 
latter in finely divided inert solid carriers such as talc, chalk, gypsum, 
vermiculite, bentonite and the like, fuller's earth, attapulgite and other 
clays, various solid detergent dispersing agents and solid fertilizer 
compositions. In preferred method of preparing such compositions, the 
carrier is mechanically ground with one or more solid phosphoroamide 
compounds; wet with one or more liquid phosphoroamide compounds; or wet 
with a solution or dispersion of one or more solid or liquid 
phosphoroamide compounds in a volatile organic solvent. Depending upon the 
proportions of ingredients, these compositions can be employed without 
further modification or be considered concentrates and subsequently 
further diluted with solid surface active dispersing agents, talc, chalk, 
gypsum or the like to obtain the desired treating composition. 
Furthermore, such concentrate compositions can be dispersed in water with 
or without added dispersing agent or agents to prepare aqueous soil 
treating compositions. 
The required amount of the one or more phosphoroamide compounds 
contemplated herein may be applied per acre treated in from about 1 to 
about 200 gallons or more of liquid carrier and/or diluent or in from 
about 5 to about 500 pounds of inert solid carrier and/or diluent. The 
concentration in the liquid concentrate will usually vary from about 10 to 
about 95 percent by weight and in the solid formulations from about 0.5 to 
about 90 percent by weight. Satisfactory sprays, dusts, or granules for 
general use contain from about 1/4 to about 15 pound of active one or more 
phosphoroamide compounds per acre. 
The compounds contemplated herein prevent or retard the urease catalyzed 
hydrolysis of urea, and they have relatively high residual activity. With 
respect to plants they have a high margin of safety in that when used in 
sufficient amount to inhibit the activity of urease, they do not burn or 
injure the plant, and they resist weathering which includes wash-off 
caused by rain, decomposition by ultra-violet light, oxidation, or 
hydrolysis in the presence of moisture or, at least such decomposition, 
oxidation, and hydrolysis as would materially decrease the desirable 
urease inhibiting characteristic of the compounds or impart undesirable 
characteristics, for instance, phytotoxicity, to the compounds. The 
compounds are so chemically inert that they are compatible with 
substantially any other constituents of the spray schedule, and they may 
be used in the soil, upon the seeds, or the roots of plants without 
injuring either the seeds or roots of plants. 
While the composition and method of this invention are particularly suited 
for agricultural applications for prevention or inhibition of urease 
catalyzed hydrolysis of urea, they can also be used in other applications 
where inhibition of the activity of urease is desired. For example, such 
other applications include use in animal litters, as feed additives, 
diaper treatments, pharmaceutical applications, urease inhibition in 
mammalian urinary tracts, and the like. It should be noted that the 
particular active compound employed in one application may not necessarily 
be useful in another application. Thus, in the selection of a particular 
active material for use in an application, such factors as toxicity of the 
material, the environment in which the material will be used, level of 
urease inhibition desired and the like must be considered in selecting 
such material. 
The novel phosphoroamide compounds of this invention which are useful as 
urease inhibitors in the composition and method of this invention are 
those of the formula: 
##STR3## 
wherein: 
R.sub.1 and R.sub.2 are the same or different and are hydrogen or alkyl 
having from 1 to about 4 carbon atoms; 
R.sub.3 is oxygen or sulfur; and 
X, Y and Z are the same or different and are hydrogen, alkyl, arylamino, 
diarylamino, halogen, hydroxy, mercapto, alkylmercapto, 
O-diaminophosphinyl, S-diaminophosphinyl, N-diaminophosphinyl, 
diaminophosphinyl, amino, cyano, nitro, alkylamino, dialkylamino, 
arylmercapto, isocyano, isocyanato, trihalomethyl, alkoxy, thiocyano, 
alkanoyl, or any two X, Y, and Z group together may form an alkylene or 
alkenylene chain which may optionally include one or more divalent oxygen, 
nitrogen, or sulfur moieties forming a 3, 4, 5, or 6 membered fused ring 
structure. 
Illustrative of permissible X, Y and Z substituents are hydrogen; alkyl, 
such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, hexyl, 
neopentyl and the like; halogen such as chloro, bromo, fluoro or iodo; 
alkylmercapto and arylmercapto, such as methylmercapto, ethylmercapto, 
propylmercapto, phenylmercapto and the like; amino or alkyl or aryl 
substituted amino, such as methylamino, dimethylamino, ethylmethylamino, 
phenylamino and the like; trihalomethyl, such as trifluoromethyl, 
trichloromethyl and the like; alkoxy, such as methoxy, ethoxy, propoxy, 
butoxy and the like; alkanoyl such as acetyl, butanoyl, hexanoyl and the 
like, and other substituents within the scope of the aforementioned 
structural formula. 
Examples of useful R.sub.1 and R.sub.2 substituents are hydrogen and alkyl 
such as methyl, ethyl, propyl and butyl. 
The following compounds are illustrative of phosphoroamide compounds within 
the scope of the generic formula set forth above which can be prepared in 
accordance with the procedures set forth hereinbelow and which can be 
employed in the practice of this invention. 
5-Tert-butyl-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
4,6-Di-tert-butyl-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
4-Methyl-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
5-Isopropyl-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
4,7-Dimethyl-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
4,6-Diisopropyl-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
4-Chloro-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
3-Bromo-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
4,6-Dichloro-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
4-Fluoro-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
5-Nitro-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
5-Cyano-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
5-Chloro-4-methyl-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
4-Methoxy-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
5-Ethylmercapto-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
4-Bromo-5-methoxy-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
5,6-Dimethoxy-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
5-Phenyl-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
5-(N,N-Dimethylamino)-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
5-(N,N-Diphenylamino)-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
5-Acetyl-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
5-Amino-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
5-Phenylmercapto-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
4-Chloro-5-nitro-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
5-Iodo-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
4,7-Dichloro-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
5-Benzyl-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
4-Methyl-6-tert-butyl-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
4-Octyl-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
5-Dodecyl-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
3-Hydroxy-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
4-Hydroxy-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
4,7-Difluoro-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
4-Chloro-5-fluoro-2-amine-2-oxide-1,3,2-benzodioxaphosphole 
2-Amine-2-thio-1,3,2-benzodioxaphosphole 
5-Tert-butyl-2-amine-2-thio-1,3,2-benzodioxaphosphole 
4,6-Di-tert-butyl-2-amine-2-thio-1,3,2-benzodioxaphosphole 
4-Methyl-2-amine-2-thio-1,3,2-benzodioxaphosphole 
4,7-Dimethyl-2-amine-2-thio-1,3,2-benzodioxaphosphole 
4,6-Diisopropyl-2-amine-2-thio-1,3,2-benzodioxaphosphole 
5-Isopropyl-2-amine-2-thio-1,3,2-benzodioxaphosphole 
4-Chloro-2-amine-2-thio-1,3,2-benzodioxaphosphole 
4-Fluoro-2-amine-2-thio-1,3,2-benzodioxaphosphole 
5-Nitro-2-amine-2-thio-1,3,2-benzodioxaphosphole 
4-Chloro-5-nitro-2-amine-2-thio-1,3,2-benzodioxaphosphole 
5-Methoxy-2-amine-2-thio-1,3,2-benzodioxaphosphole 
4-Iodo-2-amine-2-thio-1,3,2-benzodioxaphosphole 
3-Methylmercapto-2-amine-2-thio-1,3,2-benzodioxaphosphole 
5-Acetyl-2-amine-2-thio-1,3,2-benzodioxaphosphole 
4,7-Dichloro-2-amine-2-thio-1,3,2-benzodioxaphosphole 
Thiophosphorodiamidic acid 
4-(2-amine-2-thio-1,3,2-benzodioxaphosphole)ester 
Thiophosphorodiamidic acid 
4-(2-amine-2-thio-1,3,2-benzodioxaphosphole)ester 
Preferred for use in the practice of this invention are phosphoroamide 
compounds in which: 
R.sub.3 is oxygen; 
R.sub.1 and R.sub.2 are individually hydrogen or methyl; and 
X, Y and Z are individually hydrogen, diaminophosphinyl, 
N-diaminophosphinyl, S-diaminophosphinyl, N-diaminophosphinyl, alkyl, 
amino, alkoxy, nitro and trifluoromethyl. 
Particularly preferred for use in this invention are compounds in which: 
R.sub.3 is oxygen; 
X is alkyl, N-diaminophosphinyl, S-diaminophosphinyl, N-diaminophosphinyl, 
or diaminophosphinyl; and 
R.sub.1, R.sub.2, Y and Z are hydrogen. 
Among these particularly preferred compounds, most preferred are those 
compounds in which: 
R.sub.3 is oxygen; 
R.sub.1, R.sub.2, Y and Z are hydrogen; and 
X is alkyl having from 1 to 4 carbon atoms, hydrogen, O-diaminophosphinyl 
or N-diaminophosphinyl. 
Especially effacious compounds for use in the practice of this invention 
are phosphorodiamidic acid 2-amine-2-oxide-1,3,2-benzodioxaphosphole 
ester; phosphorodiamidic acid 
4-(2-amine-2-oxide-1,3,2-benzodioxophosphole)ester; and phosphorodiamidic 
acid 5-(2-amine-2-oxide-1,3,2-benzodioxaphosphole)ester. 
Compounds which are useful in the practice of this invention can be 
prepared in accordance with the following reaction scheme: 
##STR4## 
in which X, Y, Z, R.sub.1, R.sub.2, and R.sub.3, are as defined 
hereinabove. 
The aforementioned reaction scheme is described in more detail in East 
German Patent No. 128,315, Roth, H. J., et al., Synthesis of Phenyl 
Phosphorodiamidates. Part I., Arch. Pharm., 314, pp. 85-91, (1980) and 
references cited therein, V. V. Katyshkina and M. Ya. Kraft, J. Gen. Chem. 
USSR 26, 3407-12 (1956), and L. G. Dulog, et al. in U.S. Pat. Nos. 
3,767,733 (1973) and 3,812,033, (1974) and references cited therein. 
Accordingly this reaction scheme will not be described herein in any great 
detail. 
Briefly stated, in each step of the two step reaction sequence, 
substantially equal molar amounts of the reactants or excesses thereof are 
contacted neat or in an inert solvent, optionally, in the presence of a 
hydrogen chloride acceptor. Inert solvents which can be used in this 
reaction include benzene, ethyl ether, toluene, tetrahydrofuran, xylene, 
dioxane, methylene chloride, dimethylformamide, carbon tetrachloride, 
methyl sulfoxide and the like. 
Useful hydrogen chloride acid acceptors can be either inorganic or organic 
bases. Suitable acid acceptors include alkali metal carbonates such as 
sodium and potassium carbonates, but preferably tertiary amines such as 
pyridine, triethylamine, trimethylamine, isoquinoline, lutidine, 
tributylamine, 1,4-diazabicyclo[2,2,2]octane, N-ethyl piperidine, 
quinoline and the like. Alternatively, an excess of the amine reactant is 
used as the acid acceptor. 
Reaction temperatures are not critical and can be varied widely. For 
example, the reaction can be conveniently carried out in a temperature of 
from about -20.degree. C. to about 200.degree. C., but is preferably 
carried out at a temperature of from about 25.degree. C. to about 
125.degree. C. 
Similarly, reaction pressures are not critical and can be varied widely. 
For example, the reaction can be carried out at sub-atmospheric, 
atmospheric or super-atmospheric pressure. However, for convenience, the 
reaction is carried out at atmospheric or autogeneous pressure. 
The order in which the various reagents are reacted as indicated in the 
above reaction sequence is only for illustrative purposes, and the order 
of reaction is not critical. 
The exact proportions of the reactants are not critical, some of the 
desired product being obtained when the reactants are employed in any 
proportions. However, in going to completion, the reaction consumes the 
reactants and the hydrogen chloride acceptor in equimolar proportions and 
the use of the reactants and the hydrogen chloride acceptor in such 
proportions is preferred. 
Reaction times are not critical and can vary widely, depending on a number 
of factors including but not limited to reaction temperature, and the 
reactivities of the various reactants. The mixture is held within the 
desired reaction temperature range for a period of time, conveniently from 
about 1 to about 24 hours before cooling. Good yields are obtained with 
reaction times of about 4 to about 5 hours. 
During the reaction, the hydrochloride salt of the hydrogen chloride 
acceptor forms and may precipitate from the mixture. This salt can be 
removed by such conventional procedures as extraction, filtration or 
centrifugation. The phosphoroamide compound can be separated by such 
conventional procedures as evaporation and purified by conventional 
procedures such as distillation and extraction. The product separated as 
described above may be employed in the control of urease in soil or may be 
further purified by conventional procedures such as extraction and 
distillation.

The following specific examples are presented to more particularly 
illustrate the invention. 
EXAMPLE I 
Preparation of 2-Amine-2-oxide-1,3,2-benzodioxaphosphole 
A. A stirred mixture of 33.0 g (0.30 mol) of catechol, 110 ml (184 g, 1.2 
mol) of phosphorus oxychloride, and 0.99 g of potassium chloride was 
heated in a flask equipped with a condenser attached to a sodium hydroxide 
trap separated by a drying tube. The solution became homogeneous at about 
100.degree. C. and evolution of hydrogen chloride began shortly 
thereafter. The mixture was heated at reflux (110.degree. C.) for 8 h, and 
then excess phosphorus oxychloride was removed by vacuum distillation. The 
sticky, cream colored residue was washed with 9:1 ether-hexane, filtered, 
and dried under vacuum over P.sub.2 O.sub.5 at 35.degree. C. to give 33 g 
(65%) of still somewhat sticky solid, mp 107.degree.-125.degree. C.; 
.sup.1 H NMR (CDCl.sub.3):.delta.6.92 (main s) with shoulders at 7.01, 
7.12, and 7.25 ppm. 
B. The crude solid from above was stirred with 1000 mL of methylene 
chloride, filtered to remove about 4.5 g of residue, and the filtrate was 
placed in an addition funnel. The filtrate was then added dropwise to 750 
mL of cold (0.degree. C.) ether which was continually saturated with 
ammonia gas. The addition was complete in 1.5 h, and then stirring and 
ammonia addition were continued for another 30 minutes during which time 
the ice bath was removed. The mixture was filtered, washed well with 
ether, and then dried under nitrogen to give 19.4 g of product 
contaminated with ammonium chloride. A portion of this material was washed 
with ice-water to give (with much loss of product) a white solid, mp 
125.degree.-150.degree.; .sup.1 H NMR (DMSO-d.sub.6): .delta. 6.61 (br s, 
2, ArH) and 5.05 ppm (br s, 1 NH.sub.2). 
EXAMPLE II 
Preparation of Phosphorodiamidic Acid 
4-(2-Amine-2-oxide-1,3,2-benzodioxaphosphole)Ester 
A. A stirred mixture of 37.8 g (0.30 mol) of pyrogallol, 138 mL (230 g, 1.5 
mol) of phosphorus oxychloride, and 0.9 g of potassium chloride was heated 
in a flask equipped with a condenser attached to a sodium hydroxide trap 
separated by a drying tube. The pyrogallol dissolved immediately in the 
phorphorus oxychloride to give a clear solution. The solution turned pink, 
however, upon heating. Evolution of hydrogen chloride began at about 
90.degree. C. The mixture was heated at reflux (110.degree. C.) for 16 h 
by which time it had solidified into a pink-white mass. The solid was 
broken-up into a powder under pentane, filtered, washed well with pentane 
and then ether, and dried under vacuum over P.sub.2 O.sub.5 at 70.degree. 
C. The slightly pink solid partially melted from 235.degree.-265.degree. 
C., and was mostly insoluble in common organic solvents. An .sup.1 H NMR 
(acetone-d.sub.6) showed a multiplet at .delta. 6.70 ppm. 
B. A solution of 1500 mL of cold (0.degree. C.) ether continuously 
saturated with ammonia gas was prepared in a flask equipped with a 
condenser, a mechanical stirrer, and an adapter containing a wide-mouth 
funnel and a side-arm inlet for nitrogen. The solid from step A was added 
through the funnel over a 30 min. period, while a nitrogen stream was 
maintained to keep the ammonia gas away from the solid. The mixture was 
stirred vigorously for another 1.5 h at 0.degree. C., and then for 1 h 
after removal of the ice-bath. The ammonia flow was continued throughout 
the stirring period. The solids were collected by filtration, washed with 
ether, and dried under nitrogen. The crude product was quite water soluble 
and the .sup.1 H NMR (D.sub.2 O) showed two multiplets at .delta. 6.90 and 
6.82 ppm superimposed over a broad singlet at about .delta.7.2-6.6 ppm 
(NH). The crude product was separated from ammonium chloride by stirring 
with 1000 mL of acetone for 30 min. The ammonium chloride was removed by 
filtration, and the filtrate was evaporated to provide 39 g (49%) of the 
crude product as an oily solid. The crude product was further purified by 
dissolving it in 200 mL of acetone and adding this solution dropwise to 
1700 mL of ether. The resulting solid was collected by filtration, washed 
with ether, and dried over P.sub.2 O.sub.5 in a vacuum at 70.degree. C. to 
give 25 g of an almost white powder, mp 110.degree.-123.degree. C. (dec); 
.sup.1 H NMR (DMSO-d.sub.6) .delta.7.0-6.0 (m, 3, ArH) and 5.9-4.3 ppm (br 
s, 6, NH.sub.2). 
EXAMPLE III 
Preparation of Phosphorodiamidic Acid 
5-(2-Amino-2-oxide-1,3,2-benzodioxaphosphole)Ester 
A. A stirred mixture of 3.4 g (0.027 mol) of 1,2,4-trihydroxybenzene, 25 mL 
(41.4 g, 0.27 mol) of phosphorus oxychloride, and 0.100 g of potassium 
chloride was heated in a flask equipped with a condenser attached to a 
sodium hydroxide trap separated by a drying tube. The solid dissolved at 
about 80.degree. C. to give a dark colored solution, and evolution of 
hydrogen chloride shortly thereafter. The mixture was heated at reflux 
(110.degree. C.) for 10 h and then cooled to room temperature to give an 
almost white precipitate. The mixture was diluted with 20 mL of carbon 
tetrachloride, filtered, and the solid washed with carbon tetrachloride. 
The solid was too insoluble to take an NMR and too sticky to get a good 
melting point. 
B. The solid from Step A was added to 200 mL of cold (0.degree. C.) ether 
continuously saturated with ammonia gas using the apparatus and procedure 
described in Example II, Step B. The resulting white solid was very water 
soluble, but insoluble in organic solvents. It was thus used as obtained 
as a mixture with ammonium chloride: .sup.1 H NMR (D.sub.2 O): .delta. 
7.4-6.7 and 6.7-6.3 (ppm) (m, ArH). 
EXAMPLE IV 
Urease Inhibition Efficacy Test 
Efficacy tests were conducted to evaluate the efficacy of representative 
compounds as urease inhibitors. The inhibition tests were run in a New 
York soil (Cazenovia silt loam, pH 7.0). Evaluations (run in triplicate) 
consisted of applying 800 micrograms of the test compound in 5 mL of water 
and 42.8 mg of urea in 1 mL of water to 20 g of air-dry soil in a glass 
bottle. The bottle was capped with perforated aluminum foil and incubated 
at 25.degree. C. for three days prior to extraction with 100 mL of a 2M 
KCl solution containing 0.5 mg of phenylmercuric acetate. The extracts 
were then analyzed for remaining urea using an autoanalyzer. Percent 
inhibition was calculated as 
##EQU1## 
where A is urea recovered from an unincubated sample (urea added to soil 
and immediately extracted); B is urea recovered from an inhibited sample; 
and C is urea recovered from the control (uninhibited sample). 
The results of these tests are set forth in the following Table I. 
TABLE 1 
______________________________________ 
% Inhibition 
Experiment 40 micrograms per 
Number Compounds gram Cazenovia soil 
______________________________________ 
1 Phosphorodiamidic Acid 
54 
2-Amine-2-oxide-1,3,2- 
benzodioxaphosphole Ester 
2 Phosphorodiamidic Acid 
5 
4-(2-Amine-2-oxide-1,3,2- 
benzodioxaphosphole) Ester 
3 Phosphorodiamidic Acid 
21 
5-(2-Amine-2-oxide-1,3,2- 
benzodioxaphosphole) Ester 
______________________________________