WO2013052279A2 - Tampons biologiques ayant de larges plages de tamponnage - Google Patents

Tampons biologiques ayant de larges plages de tamponnage Download PDF

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WO2013052279A2
WO2013052279A2 PCT/US2012/056190 US2012056190W WO2013052279A2 WO 2013052279 A2 WO2013052279 A2 WO 2013052279A2 US 2012056190 W US2012056190 W US 2012056190W WO 2013052279 A2 WO2013052279 A2 WO 2013052279A2
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buffers
synthesis
shows
amine
zwitterionic
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PCT/US2012/056190
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WO2013052279A3 (fr
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Thomas Daly
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Thomas Daly
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Priority claimed from US13/267,440 external-priority patent/US8519141B2/en
Priority claimed from US13/588,530 external-priority patent/US8822728B2/en
Application filed by Thomas Daly filed Critical Thomas Daly
Publication of WO2013052279A2 publication Critical patent/WO2013052279A2/fr
Publication of WO2013052279A3 publication Critical patent/WO2013052279A3/fr

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    • C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
    • C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C215/04—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated
    • C07C215/06—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic
    • C07C215/10—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic with one amino group and at least two hydroxy groups bound to the carbon skeleton
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    • C07C211/02—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
    • C07C211/09—Diamines
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    • C07C211/02—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
    • C07C211/13—Amines containing three or more amino groups bound to the carbon skeleton
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    • C07C215/06—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic
    • C07C215/12—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic the nitrogen atom of the amino group being further bound to hydrocarbon groups substituted by hydroxy groups
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    • C07C215/04—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated
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    • C07C215/18—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic with hydroxy groups and at least two amino groups bound to the carbon skeleton
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    • C07C215/74—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
    • C07C215/90—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with quaternised amino groups bound to the carbon skeleton
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    • C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C217/06—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted
    • C07C217/08—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to an acyclic carbon atom
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    • C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C217/28—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having one amino group and at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the carbon skeleton, e.g. ethers of polyhydroxy amines
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    • C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C229/06—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton
    • C07C229/10—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings
    • C07C229/12—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of acyclic carbon skeletons
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    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C229/06—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton
    • C07C229/10—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings
    • C07C229/16—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of hydrocarbon radicals substituted by amino or carboxyl groups, e.g. ethylenediamine-tetra-acetic acid, iminodiacetic acids
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    • C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C229/22—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated the carbon skeleton being further substituted by oxygen atoms
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    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C229/24—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having more than one carboxyl group bound to the carbon skeleton, e.g. aspartic acid
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    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C237/06—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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    • C07C305/04—Esters of sulfuric acids having oxygen atoms of sulfate groups bound to acyclic carbon atoms of a carbon skeleton being acyclic and saturated
    • C07C305/10—Esters of sulfuric acids having oxygen atoms of sulfate groups bound to acyclic carbon atoms of a carbon skeleton being acyclic and saturated being further substituted by singly-bound oxygen atoms
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    • C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
    • C07C309/01—Sulfonic acids
    • C07C309/02—Sulfonic acids having sulfo groups bound to acyclic carbon atoms
    • C07C309/03—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
    • C07C309/13—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton
    • C07C309/14—Sulfonic acids having sulfo groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton containing amino groups bound to the carbon skeleton
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    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/06—Phosphorus compounds without P—C bonds
    • C07F9/08—Esters of oxyacids of phosphorus
    • C07F9/09—Esters of phosphoric acids
    • C07F9/091—Esters of phosphoric acids with hydroxyalkyl compounds with further substituents on alkyl
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    • C07F9/02—Phosphorus compounds
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    • C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
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Definitions

  • the present invention relates generally to the field of amines and more particularly to a classes of amines used as buffers in biological systems.
  • Amines are very useful compounds in the buffering of biological systems.
  • Each class of amine has various limitations which require choosing an amine based on multiple factors to select the best amine.
  • pH buffering range is typically most important, but issues of chelation, and pH range stability, and solubility also come into play.
  • a suboptimal buffer will result in yields that are well below the potential yield. The invention disclosed improves the yields in
  • the present invention relates to amines and amine derivatives that improve the buffering range, and / or reduce the chelation and other negative interactions of the buffer and the system to be buffered.
  • the reaction of amines or polyamines with various molecules to form polyamines with differing pKa's will extend the buffering range, derivatives that result in polyamines that have the same pKa yields a greater buffering capacity.
  • Derivatives that result in zwitterionic buffers improve yield by allowing a greater range of stability.
  • Fig. 1 shows the derivation of polyamines and zwitterionic buffers from tromethamine.
  • Fig. 2 shows the derivation of zwitterionic buffers and polyamines from aminomethylpropanol.
  • Fig. 3 shows the reaction of 2-methyl-2-nitro-1 -propanol with acrylonitrile and its derivatives.
  • Fig. 5 shows the reaction of 2-nitro-2-methyl-1 ,3-propanediol with
  • acrylonitrile and its derivatives where x,y,and n are all integers where x and y are chosen independently, such that x+y n and n is greater than zero.
  • Fig. 8 shows the reaction of 2-nitro-1 -butanol with acrylonitrile and its derivatives.
  • Fig. 9 shows Figure 9 shows alkoxylation of aminomethylpropanol.
  • Fig. 10A shows the synthesis of a very mild, high foaming, surfactant derived from MCA.
  • Fig. 10B shows the synthesis of a very mild, high foaming, surfactant derived from SVS.
  • Fig. 11 shows the synthesis of a series of buffers with 2-nitropropane as the starting material.
  • Fig. 12 shows Figure 12 shows the synthesis of a series of buffers with 1 - nitropropane as a starting material where n and m are integers where m+n is greater than zero and n is greater than or equal to m.
  • Fig. 13 shows the synthesis of a series of buffers with nitroethane as a starting material where n and m are integers where m+n is greater than zero and n is greater than or equal to m.
  • Fig. 15 shows the synthesis of a series of zwitterionic buffers based on acrylic acids.
  • Fig. 16 shows the synthesis of a zwitterionic sulfonate based on
  • Fig. 17 shows the synthesis of a zwitterionic sulfonate based on
  • Fig. 18 - 25 show the synthesis of families of zwitterionic buffers from nitroalcohols.
  • Fig. 26 shows the synthesis of zwitterionic buffers from morpholine.
  • Fig. 27 shows the synthesis of zwitterionic buffers from hydroxyethyl piperazine.
  • Fig. 28 shows the synthesis of zwitterionic buffers from piperazine.
  • Fig. 29 shows the synthesis of zwitterionic buffers from ethyleneamines.
  • Fig. 30 shows the synthesis of a zwitterionic buffer with primary, secondary, tertiary, or quaternary amine functionality.
  • Fig. 31 - 33 show the synthesis of mild zwitterionic surfactants from nitroalcohols.
  • Fig. 34 - 37 show the synthesis of polyamines from nitroalcohols.
  • Fig. 38 shows the synthesis of diamines from nitroalcohols
  • Fig. 39 shows the synthesis of isopropyl amine acrylate buffers and mild surfactants.
  • Fig. 40 shows the synthesis of zwitterionic buffers from SVS and MCA derived from isopropyl amine as well as mild surfactants and diamines.
  • Fig. 41 shows the synthesis of a sultaine zwittterionic buffer of isopropyl amine.
  • Fig. 42 shows the synthesis of zwitterionic buffers from amino alcohols and itaconic acid.
  • Fig. 43 shows the synthesis of nitro acids from nitroalcohols and itaconic acid.
  • Fig. 44 shows the synthesis of primary amino zwitterionic buffers from nitro acids.
  • Fig 45 shows the synthesis of a family of zwittenonic buffers from itaconic acid and amines.
  • Fig. 46 shows the synthesis of surfactants from amines and itaconic acid intermediates.
  • Fig. 47 shows the synthesis of nitroacids from nitroparaffins and itaconic acid.
  • Fig. 48 shows the synthesis of zwitterionic buffers from nitro acids.
  • Fig. 49 shows the synthesis of zwitterionic buffers from 4-aminopyridine.
  • Fig. 50 shows the synthesis zwitterionic buffers from the ketimine
  • Fig. 51 shows the synthesis of zwiiterionic sultaines from 4-aminopyridine.
  • Fig. 52 shows the synthesis of zwitterionic buffers from taurine.
  • Fig. 53 shows the synthesis of zwitterionic buffers from homotaurine.
  • Fig. 54 shows the synthesis of zwitterionic buffers from aspartic acid.
  • Fig. 55 shows the synthesis of sultaine zwitterionic buffers from sodium bisulfite and epichlorohydrin.
  • Fig. 56 shows the synthesis of sultaine zwitterionic buffers from sodium bisulfite, epichlorohydrin, and aminoalcohols.
  • Fig. 57 shows the synthesis of zwitterionic buffers from propane sultone
  • Fig. 58 shows the synthesis of amidoamine buffers from acrylamide.
  • Fig. 59 shows the syntheis of amidoamine buffers from methacrylamide.
  • Fig. 60 shows the synthesis of amidoamine buffers from taurines and diamines.
  • Fig. 61 shows the synthesis of zwitterionic amidoamine buffers from propone sultone and SVS.
  • Fig. 62 shows the synthesis of sultaine amidoamine zwitterionic buffers.
  • Fig. 63 shows the synthesis of a family of coumpounds as zwitterionic buffers and products that are expected to be useful as multiple sclerosis and spinal cord injury therapies.
  • Fig. 64 shows amide based zwitterionic buffers and products that are expected to be useful as multiple sclerosis and spinal cord injury therapies.
  • Fig. 65 shows additional zwitterionic buffers based on 4-aminopyridine amides. These products are also expected to be useful as multiple sclerosis and spinal cord injury therapies.
  • Fig. 66 shows the synthesis of zwitterionic buffers that are also expected to be useful as multiple sclerosis and spinal cord injury therapies. Most of this family has increased hydrogen bonding and is based on the MCA derived zwitterionic buffers disclosed herein.
  • Fig. 67 shows the synthesis of zwitterionic buffers that are also expected to be useful as multiple sclerosis and spinal cord injury therapies. Most of this family has increased hydrogen bonding and is based on the acrylic acid derived zwitterionic buffers disclosed herein.
  • Fig. 68 shows the synthesis of zwitterionic buffers that are also expected to be useful as multiple sclerosis and spinal cord injury therapies. Most of this family has increased hydrogen bonding and is based on the methacrylic acid derived zwitterionic buffers disclosed herein.
  • Fig. 69 shows the synthesis of zwitterionic buffers that are also expected to be useful as multiple sclerosis and spinal cord injury therapies. Derived from ethylene amines.
  • Fig. 70 shows the synthesis of amidoamine buffers that are stearicly hindered.
  • Fig. 71 shows the synthesis of amidoamine buffers that are stearicly hindered with extensive hydrogen bonding.
  • Fig. 72 shows the synthesis of amidoamine buffers.
  • Fig. 73 shows that any of the amidoamine buffers taught herein, maybe reduced to aminoalcohols or diamines.
  • Fig. 74 shows the esterification of the zwitterionic buffers.
  • Fig. 75 shows the esterification, mono- and diesterification of the itaconic acid based zwitterionics.
  • Fig. 76 shows the synthesis of diacid, tertiary amine, zwitterionic buffers.
  • Fig. 77 shows the synthesis of amido amines from zwitterionic buffers.
  • Fig. 78 shows the synthesis of a variety of 4-aminopyridine derivatives that are useful buffers.
  • Fig. 79 shows the condensation polymerization of the hydroxyl functional zwitterionics.
  • Fig. 80 clarifies the amidoamine to aminoalcohol or diamine synthesis originally outlined in Figure 73.
  • Fig. 81 - 84 teach the synthesis of sulfonamides from the zwitterionic buffers.
  • Fig. 85 shows the synthesis of quaternary amine salts from tertiary
  • Fig. 86 -87 teach the synthesis of sulfonate esters of the zwitterionic buffers.
  • Fig. 88 - 89 teach the synthesis of amino acid, zwitterionic buffers with primary amine functionality.
  • Fig. 90 expands on the quaternary amine salts shown in Fig. 85.
  • Fig. 91 - 92 show the use of acrylate hydroxyesters in the synthesis of biological buffers.
  • Fig. 93 teaches the synthesis of a family of phosphonates and phosphonate amino acids.
  • Fig. 94 teaches the synthesis of a family of phosphamides.
  • Fig. 95 teaches the synethsis of zwitterionic buffers based on MCA and sulfonic acids.
  • Fig. 96 teaches the synthesis of an enzyme inhibitor.
  • Fig. 97 teaches the synthesis of diacid sulfonic acid buffers.
  • Fig. 98 teaches diacid buffers with sulfonic acid and phosphonate
  • Fig. 99 teaches diacid buffers with sultaine and carboxcylic acid functionality.
  • Fig. 100 - 101 teach the reduction of the zwitterionic buffers to alcohols and ethers.
  • Fig. 102 - 104 teaches the synthesis of zwitterionic buffers and their reduction to alcohols and ethers.
  • Fig. 105 teaches the synthesis of sulfonamide buffers.
  • Fig. 106 teaches the synthesis of mono and disubtituted Michael additions to form zwitterionic buffers.
  • Fig. 107 teaches the synthesis of a new class of amines and aminoalcohols and their derivatives.
  • Fig. 108 teaches the synthesis of a new class of amines and aminoalcohols and derivatives of nitro compounds and valeraldehyde.
  • Fig. 109 teaches the synthesis of a new class of aminoalcohols and their derivatives based on monosubtitution of gluteraldehyde and nitro compounds.
  • Fig. 110 - 111 teaches the synthesis of diamines and their derivatives based on gluteraldehyde and nitro compounds.
  • Fig. 112 - 113 teach the synthesis of a class of amino alcohols derived from glucose and nitro compounds and their derivatives.
  • Fig. 114 -115 teach the synthesis of banzaldehyde and nitro compounds and their derivatives.
  • Fig. 116 teaches how dimmers can be formed when using a nitro compound with more than one hydrogen on the nitro containing carbon.
  • Fig. 117 teaches how dialdehydes can be used to make dimmers and polymers.
  • Fig. 118 teaches a novel route to nitro acids and primary amino acids of several types.
  • Fig. 119 teaches the synthesis of surfactants based on aldehydes and nitro compounds.
  • Fig. 120 expands Figure 107 to cover an additional species where the aldehyde is acetaldehyde in which E -CH 3 .
  • MCA monochloroacetic acid
  • SVS sodium vinyl sulfonate
  • n may equal any integer greater than zero, including 1 .
  • this selection can take place in adding acrylonitrile to the amine that results, allowing a progressively more branched product. It is within the scope of the invention disclosed herein to include these additional types of products and their subsequent derivatives described herein.
  • Figure 1 shows the addition of only one mole of SVS or MCA, it is known in the art, that a second mole may be added to obtain a product with a second zwitterionic group. Furthermore, in the case where the product has repeated additions of acrylonitrile and reduction to the amines, the branched products may have many more zwitterionic groups. Also, it is to be noted that, while the sulfonates are shown as sodium salts, other salts and the free acids (non-salted form) are also within the scope of this invention.
  • amines that would make excellent starting materials in place of tromethamine are 2-amino-2-methyl-1 -propanol, 2-amino-1 -butanol, 2-amino-2-ethyl- 1 ,3-propanediol, 2-amino-2-methyl-1 ,3-propanediol, and
  • fatty amines such as lauryl amine, coco amine, tallow amine, and oleoyl amine
  • fatty ether amines such as bis-(2-hydroxyethyl) isodecyloxypropylamine
  • FIG. 2 Other amines that are shown in Figure 2 are produced via a similar series of reactions, except that figure 2 includes zwitterionic buffers from the amine 2-amino-2- methyl-1 -propanol, as well as the polyamines derived from the reaction with acrylonitrile and the subsequent derivatives described above.
  • Other amines can be utilized in addition to 2-amino-2-methyl-1 -propanol to obtain excellent buffers are 2- amino-1 -butanol, 2-amino-2-ethyl-1 ,3-propanediol, 2-amino-2-methyl-1 ,3- propanediol, and dihydroxymethylaminomethane.
  • Reaction conditions could be created such that the alcohol groups on the amines listed above could be reacted with acrylonitrile as well, and then reduced to the amines and, if desired, reacted with SVS or MCA to impart zwitterionic character.
  • Polyamines with good properties for use in biological fermentations, purifications, storage and general handling can also be produced through the reaction of nitroalcohols and acrylonitrile, followed by reduction. Additional derivatization with SVS or MCA will result in zwitterionic buffers with a very large buffering range and capacity.
  • Figure 3 shows the reaction of 2-methyl-2-nitro-1 -propanol with acrylonitrile and its derivatives.
  • Figure 5 shows the reaction of 2-nitro-2-methyl-1 ,3-propanediol with
  • acrylonitrile and its derivatives where x,y,and n are all integers where x and y are chosen independently, such that x+y n and n is greater than zero.
  • FIG. 6 shows the reaction of tris(hydroxymethyl)nitromethane with
  • acrylonitrile and its derivatives where x,y, z, and n are all integers where x, y and z are chosen independently, such that x+y+z n and n is greater than zero.
  • Figure 8 shows the reaction of 2-nitro-1 -butanol with acrylonitrile and its derivatives.
  • Figures 2 through 8 are subject to the same clarifications as figure 1 with regard to the cyanoethylation and the formation of a more linear or branched structure as well as the addition of SVS or MCA in molar equivalents of primary amine groups or less than molar equivalents of primary amine groups present.
  • the buffers described thus far may also be ethoxylated, propoxylated, or butoxylated to modify their properties.
  • Ethoxylation will tend to impart surfactancy to the resulting product.
  • Propoxylation will add surfactancy, but also reduce the water solubility. This is useful in emulsion breaking and reverse emulsion breaking, this will also find utility in breaking up and dissolving biofilms. This is also desired in oilfield applications. Butoxylation will similarly shift the HLB to the hydrophobic.
  • FIG. 9 shows alkoxylation of aminomethylpropanol.
  • the direct 2 mole ethoxylation of 2- amino-2-methyl-1 -propanol with 2 moles of ethylene oxide, as shown in Figure 9 produces an excellent biological buffer with less chelation than 2-amino-2-methyl-1 - propanol.
  • the reaction of 2-amino-2-methyl-1 -propanol with propylene oxide or butylene oxide yields a similarly less chelating product, as does the reaction with diethylene glycol.
  • Figure 10 shows the synthesis of 2 very mild, high foaming, surfactants that are well suited for personal care applications were irritation is problematic, such as baby shampoo and face cleansers. Similar results are seen when 2-amino-1 - butanol, 2-amino-2-methyl-1 ,3-propanediol, 2-amino-2-ethyl-1 ,3-propanediol, tris(hydroxylmethyl)aminomethane, and 2-amino-1 ,3-propanediol are used as the starting material in place of 2-amino-2-methyl-1 -propanol.
  • FIG. 1 1 shows the synthesis of a series of buffers with 2-nitropropane as the starting material.
  • Figure 12 shows the synthesis of a series of buffers with 1 -nitropropane as a starting material where n and m are integers where m+n is greater than zero and n is greater than or equal to m.
  • Branching can be imparted on the buffers described in figures 1 1 through 14 for the polyamines that have greater than 3 amine groups by reducing the resulting nitrile or polynitrile to the polyamine and then reacting with more acrylonitrile and then reducing the resulting nitrile groups to amine groups. This can be done repeatedly. As in Figure 1 , conditions can be chosen such that a more branched product results. A more linear product is produced by simply adding all the acrylonitrile in one step, and then reducing the resulting polynitrile to the polyamine. For figures 12 through 14, the zwitterionic products can be made by adding MCA or SVS as shown in Figures 2 through 8.
  • Figure 13 shows the synthesis of a series of buffers with nitroethane as a starting material where n and m are integers where m+n is greater than zero and n is greater than or equal to m.
  • FIG. 15 shows the synthesis of a family of zwitterionic buffers based on members of the acrylic acid family.
  • vinyl acids such as acrylic, 3-butenoic acid, 4-pentenoic acid, and other carboxcylic acids with a double bond at the terminus.
  • Carboxcylic acids with a triple bond at the terminus also can be utilized, similarly, an acid where the multiple bond is not at the terminus, such as hex-4-enoic acid, can also be utilized.
  • the preferred embodiment is the vinyl acid with a double bond at the terminus.
  • One very large benefit of utilizing vinyl acids to make zwitterionic buffers is that the product does not need to be ion exchanged to produce a non-ionized form. In the market, both ionized, or sometimes called salted, and non-ionized forms sometimes called free acid or free base, are required. In situations where ionic strength must be very closely
  • the non-ionized forms are more popular.
  • the salted forms are preferred. It is understood to one skilled in the art, the present invention covers both the ionized and non-ionized forms of the buffers disclosed herein.
  • FIG. 17 Another embodiment of the present invention is the sulfonate zwitterionic buffers derived from the reaction of an amine with an epichlorohydrin and sodium bisulfate condensate as described in Figure 16. It is understood by one skilled in the art that other sulfate salts can be utilized to arrive at the desired molecular structure and is included in the present invention.
  • Figures 17 through 25 teach the flexibility of the present invention to synthesize a series of a amine sulfonate or amino acid zwitterionic buffers from nitroalcohols or alkanolamines to produce zwitterionic buffers that have primary amino functionality or secondary amino functionality. In cases where there are more than one reactive group, amine, alcohol, or a
  • multiple sulfonate groups or acid groups can be reacted by adding more than one equivalent of the vinyl acid or the oxirane containing sulfonate.
  • Another embodiment of the current invention is to make zwitterionic buffers with cylcoamines as the starting material.
  • the cycloamines result in a tertiary amino group that is less chelating and interferes less in biological functions.
  • Figure 26 shows the reaction of morpholine with a vinyl acid and morpholine with the oxirane sulfonate.
  • Figure 27 shows similar products, but utilizing hydroxyethyl piperazine.
  • Figure 28 shows the use of diamines as starting materials by using piperazine as the starting material. This is a good example of a synthesis of polyzwittterionic buffers as discussed earlier.
  • Figure 29 shows the use of ethylene amines to make zwitterionic buffers through reaction with vinyl acids or oxirane sulfonates.
  • ethylene amines such as monoethanolamine and the higher homologs, such as diethylenetriamine and is part of the invention disclosed herein.
  • FIG. 30 shows this via oxirane sulfonate and amines.
  • any primary, secondary, or tertiary amine can be used in place of the methyamines in Figure 30.
  • the resulting amines can be reacted further with vinyl acids, monochloroacetic acid, sodium vinyl sulfonate, or an oxirane sulfonate to further add acidic character to the zwitterionic buffer.
  • FIG. 31 through 33 teach the synthesis of these mild surfactants.
  • Lower molecular weight acids produce lower foaming mild surfactants, whereas higher molecular weight carboxcylic acids yield higher foam.
  • Laurie acid is the preferred embodiment for a high foaming, mild surfact.
  • Coconut fatty acid performs similarly, but at a lower cost.
  • a good surfactant with low foam can be made using octanoic acid as the carboxcylic acid.
  • Figures 34 and 35 teach the synthesis of diamines from nitroalcohols.
  • Figure 34 shows the synthesis with several hydroxyl groups present. It is understood by one skilled in the art that additional amino groups can be added by reacting more than one equivalent of epichlorohydrin to the nitroalcohol, up to the number of hydroxyl groups, and then reacting the same number of equivalents of amine to the oxirane containing amine.
  • additional amino groups can be added by reacting more than one equivalent of epichlorohydrin to the nitroalcohol, up to the number of hydroxyl groups, and then reacting the same number of equivalents of amine to the oxirane containing amine.
  • base such as caustic
  • the epichlorohydrin will preferably react with the amine as outlined in the 1 equivelent addition depicted in Figure 34 and Figure 35.
  • Figure 36 demonstrates that tertiary amines can be used to make zwitterionic buffers with quaternary amine functionality from tertiary amines. While not explicitly shown, any other tertiary amine can be used as the starting material and is part of the invention described herein.
  • Figure 37 and Figure 38 demonstrate that diamines can be made from nitroalcohols by reacting sequentially the nitroalcohol with epichlorohydrin and then the second equivalent of the nitroalcohol, followed by reduction. Also taught is that a reduction step can take place in the beginning to yield a diamine with two secondary amino groups. It is understood by one skilled in the art that the
  • nitroalcohols or alkanolamines do not need to be symmetric, but others may be used in the synthesis of the diamine and is part of the invention disclosed herein.
  • Figure 42 shows the synthesis of zwitterionic biological buffers from amino alcohols and itaconic acid. These buffers have two acid groups and increased buffering in the acidic range of pH 3 - 6.
  • Figures 43 and 44 show the synthesis of zwitterionic buffers with primary amine groups. These buffers are preferred in applications such as personal care where secondary amines are seen as
  • nitro diacids of Figure 44 also have great utility as chemical intermediates when synthesizing bioactive molecules.
  • Figure 45 shows the synthesis of a family of zwitterionic buffers from itaconic acid.
  • the buffers in Figure 45 are not limited to amino alcohols as starting materials and provide a wide range of molecular size and solubilities.
  • Figure 46 shows the synthesis of a family of amphoteric surfactants. These surfactants are preferred for there mildness, ability to perform in hard water conditions and persistent lather when in the fatty tail is approximately 10 - 12 carbons in length.
  • the R group in figure 46 is to encompass the fatty acid family of carbon chain lengths, generally from about 6 to about 22 carbons. In the specific cases illustrated of lauric amine and lauric dimethyl amine reacted with itaconic acid, it is understood by one in the art that any chain length amine can be used and is in within the scope of the invention herein.
  • fatty amines carbon lengths of about 6 to about 22 carbons, branched and linear, saturated and unsaturated
  • isopropyl amine and butyl amine isopropyl amine and butyl amine.
  • the lower carbon chain lengths produce low foaming hard surface cleaners, while the carbon chains of about 8 to 10 tend to produce the most foam.
  • Higher chain lengths find utility as mineral collectors in floatation processes such as those employed in iron and potash mining.
  • Figure 47 shows the synthesis of nitro acids from nitroparaffins. As stated early, these are very flexible intermediates, particularly when synthesizing bioactive molecules. Reduction of the nitro acids, as shown in Figure 48 produces zwitterionic buffers with primary amine character. In the case of nitroparaffins that have more than one hydrogen bound to the nitro bound carbon, more than one addition of the itaconic acid can occur. The substitution can occur up to the number of hydrogen atoms bound to the nitro bound carbon.
  • Figure 49 shows the synthesis of zwitterionic buffers from 4-aminopyridine
  • Figure 50 shows using the less stable ketimine conformation as the starting material
  • Figure 51 shows the synthesis of sultaine type buffers from 4-aminopyridine.
  • Additional buffers can be made by propoxylating and butoxylating 4-aminopyridine.
  • the ethoxylating and propoxylating will reduce the water solubility and reduce the bioavailability. This is one method of extending the time a material is bioavailable by making it available slowly, particularly if the molecule is metabolized.
  • a triamine can be made by reacting 2-aminopyridine with arcrylonitrile and reducing it to the triamine, or reacting with allylamine to keep the aromatic nature of the six membered ring.
  • the resulting buffers are excellent buffers in their own right, but also have great promise in treatment of multiple sclerosis, and other conditions that can benefit from calcium or other cation inhibition.
  • the anionic components in particular, are all groups that can chelate cations.
  • Figure 52 outlines the synthesis of taurine derived zwitterionic buffers. These molecules, along with the products in Figure 53, homotaurine derived zwitterionic buffers, are expected to find great utility in the purification of proteins and in cell culture media.
  • Figure 54 shows the synthesis of a series of zwitterionic buffers derived from aspartic acid. These compounds are expected to be very useful in electrophoresis gels as they have a unique charge density and size profile.
  • the sultaine derivatives in Figure 55 and Figure 56 are expected to find great utility in cell culture media and in purification due to their zwitterionic nature and pKa range.
  • the zwitterionic buffers of Figure 57 are expected to be primarily useful in cell culture media.
  • the buffers of Figure 58 and Figure 59 are ideally suited for use in
  • Figure 60, Figure 61 and Figure 62 show the synthesis of zwitterionic amidoamine buffers for use cell culture media and purification.
  • Figure 63 shows the synthesis of zwitterionic buffers that are expected to be useful in the treatment of multiple sclerosis (MS) and spinal cord injury by blocking potassium channels.
  • MS multiple sclerosis
  • the increased hydrogen bonding available through the sulfonate group is expected to enhance the efficacy over the traditional 4- aminopyridine therapy. While the figure shows only two compounds, one skilled in the art will recognize that any of the amino acid taurates, including, but not limted to those disclosed herein, particularly those of Figures 52, 53, 54, and 57.
  • Figures 64 and 65 show the synthesis of a further class of amidoamine buffers that are expected to be effective therapies for MS and spinal cord injury due to the pKa and hydrogen bonding.
  • Figures 66-68 shows the synthesis of a class of compounds that are excellent amidoamine buffers, particularly useful for electrophoresis and protein focusing. These are also expected to be excellent therapies for MS and spinal cord injury through potassium channel blocking. The more hydrogen bonding variants are expected to have greater efficacy.
  • Figure 69 shows the synthesis of a further class of amidomine buffers that are also expected to have utility as MS or spinal cord injury therapies.
  • amino acids used are not limited to those presented but any amino acid can be utilized and are within the scope of the present invention.
  • analogs based on methacrylic and other vinyl acids as the amino acid reacted with 4-aminopyridine are within the scope of the present invention, similar to the analogs presented in Figure 15 where tromethamine is reacted with various acids to form a family of amino acids.
  • Figures 70-72 teach a family of amidoamine buffers.
  • Figure 73 shows that any of the amidoamines presented herein, may be reduced to the aminoalcohol by reacting with hydrogen in the presence of a catalyst, such as raney nickel or raney cobalt, as well as reduced to the diamine by treatment with lithium aluminum hydride or similarly strong reducing agent.
  • the resulting amines can be reacted further with vinyl acids, monochloroacetic acid, sodium vinyl sulfonate, or an oxirane sulfonate to further add acidic character to the zwitterionic buffer.
  • salts and free acids and free bases of the compounds taught herein are within the scope of the invention.
  • the Figures 74 and 75 do not explicitly show the esterification of the products of Figure 26, but it is understood that the esterification is similar enough to be recognized by one skilled in the art.
  • the 4-aminopyridine derived zwitterionic buffers benefit from esterification in adjusting the bioavailability and water solubility, much as they do from alkoxylation, to improve their efficacy and reduce side effects when used as a therapy for MS, Alzheimer's disease, or other medical use.
  • the primary amines that are the basis for the zwitterionic buffers may undergo disubstitution to form diacid functional buffers as shown in Figure 76. These may be mono- or diesterified just as the itaconic acid based buffers in Figure 75.
  • Figure 77 expands on the amidoamines that can be synthesized from the zwitterionic buffers. The amidoamine formation may also be carried out by diamines to create dimmers, or with the secondary diamines, such as coco diamine or tallow diamine to produce surfactants that act as corrosion and scale inhibitors.
  • Figure 78 shows the synthesis of a variety of 4-aminopyridine derivatives that are useful buffers. The varying amine strength and water solubility give them unique properties.
  • Figure 79 shows the condensation polymerization of the hydroxyl functional zwitterionic buffers. As shown, linear polyesters or polyester prepolymers are produced. By using the buffers with varying hydroxyl numbers, a hydroxyl functional polymer results. When used as a prepolymer, greater cross-linking can be introduced when incorporated into a polyurea, polyurethane, or polyether. If condensed with the itaconic based buffers, such as those in Figure 42, or other polyacid functional monomers or prepolymers, a 3 dimensional polyester polymer matrix can be achieved.
  • Figure 80 further clarifies the ability to make diamines from the amides taught herein.
  • G is -OH
  • it can either remain intact when done under milder reduction conditions, or be converted to -H when harsher conditions, such as when LAH is used.
  • Figures 81 , 82, 83 and 84 demonstrate how the sulfonate buffers can be converted to sulfonamides.
  • Sulfonamides have a wide range of known biological activity and these sulfonamides are expected to have increased antimicrobial properties versus their related sulfonates or carboxcylic acid functional zwitterionics.
  • Figure 85 shows the synthesis of quaternary amine salts. These products are particularly useful in diagnostic kits for condution, as well as there antimicrobial properties.
  • Figures 86 and 87 teach the synthesis of sulfonate esters from the zwitterionic buffers. These esters allow for changing the water solubility, while maintaining buffering capacity.
  • Figures 88 and 89 teach the synthesis of zwitterionic buffers with primary amino functionality. Again, the 4-aminopyridine moiety containing buffers are promising targets for therapies to treat MS and potentially Alzheimer's disease or other diseases that involve demyelination or other myelin anomalies.
  • Fig. 90 expands on the quaternary amine salts shown in Fig. 85.
  • Figs. 91 and 92 show the synthesis of buffers with adjusted HLB by using hydroxyesters of acrylic acids.
  • Fig. 91 an example of a disubstituted amine is shown in the second line. This applies for all the amine and acrylate pairs which are within the scope of the present invention.
  • Fig. 91 in addition to showing the hydroxyester acrylates which can be made through acid catylized esterification of the acrylic acid, also show an alkoxylated acrylate.
  • the alkoxylated acrylate can be prepared through acid catalyzed alkoxylation utilizing ethylene oxide, propylene oxide, butylene oxide or any other alkoxylate.
  • the reaction product is a buffer that possesses a wide range of water solubilities.
  • Fig. 91 includes this process.
  • Fig. 93 teaches the synthesis of phosphonates based on aminoalcohols and amino acids, as well as those derived from 4-Aminopyridine. These phosphonates are excellent buffers in their own right, but have other benefits. The phosphonates have a higher solubility profile when salted with divalent cations, such as, calcium, magnesium and zinc. This also results in the molecules being excellent chelants and scale inhibitors. In addition, these phosphonates are expected to be quite
  • the amino acid starting materials in Fig. 93 exhibit fungal resistance as well as resistance moss, mold and some bacteria.
  • the 4- Aminopyridine derivatives are biologically active as treatments for MS and other autoimmune diseases, such as rheumatoid arthritis, and conditions effected by abnormal myelination.
  • the phosphonates are expected to extend this efficacy further.
  • the phosphonates, of the amino acids in particular are expected to be excellent herbicides.
  • the phosphamides of Fig. 94 show great promise as insecticides and insecticide precursors. These phophamides also show promise as chemotherapy agents for treatment of cancers. It is believed that the phosphamides taught are useful therapies for autoimmune diseases by suppressing the immune response to various antigens.
  • Figure 95 teaches the synthesis of zwitterionic sulfonates based on monochloroacetic acid.
  • Figure 96 teaches an enzyme inhibitor.
  • Figure 97 through Figure 99 teach the synthesis of diacid buffers. These buffers, while useful as buffers also possess unique biological properties, including enzyme inhibition. Thus making these very useful tools in agriculture, diagnostics, and biotechnology. It is understood by one skilled in the art that the amino acid starting materials could be substituted for their esters or alkoxylates, such as in figures 74, 86, 91 , 92, thus giving the analogous products.
  • Figure 100 outlines a family of products that are useful buffers that are primarily liquid and distillable. These products also have wider applications, specifically in removal H 2 S from both refinery processes as well as gas and liquid petroleum, products. The reduction of the carbonyl produces compounds that are more stable to the harsh conditions seen in oil and gas recovery and refinery processes.
  • the final molecule at the bottom of Figure 104 is a hindered amine that has fewer interactions than the primary amine with proteins, improving yield when used to purify proteins. It is a suitable H 2 S treating amine as well. Lines 2, 4, and 6 of Figure 100 are present simply to underscore the fact these amines used as precursors may be mono or disubstitued, as made clear in other sections.
  • Figure 101 continues to teach the reduction of the zwitterionic buffers and their esters to alcohols and ethers.
  • the sulfonic acid zwitterions if the reduction is allowed to run longer or is run under stronger reducing conditions, such as with LAH, the sulfonic acid groups will be converted to thiols. These thiols are also within the scope of the present invention.
  • Figure 102 teaches the synthesis of a range of zwitterionic buffers based on dopamine. These products, and there derivatives are excellent buffers in their own right, but also posses bioactivity, including fungal resistance.
  • Figure 103 includes sulfonamides that are particularly fungal resistant, as are the zwitterionic buffers taught.
  • Figure 104 primarily teaches the synthesis of dopamine based zwitterionic buffers and their esters. The esters expand the usefulness of the product by resulting in more hindered buffers so that there are less interactions with proteins that can destabilize their tertiary structure.
  • Figure 105 teaches the synthesis of sulfonamide and disulfonamide buffers based on the zwitterionic buffers previously taught. In addition to their buffer capability and utility in protein fermentation and purification, the sulfonamide buffers, particularly those based on 4-aminopyridine and dopamine, are expected to have use as therapeutic agents in areas where fungal infection is
  • Figure 106 demonstrates again the mono or disubtitutions that can take place with primary amines. Both species and there analog derivatives that are taught in this application are within the scope of the present invention.
  • the sulfonic acid buffers may also be synthesized as diacids analogous to the carboxcylic acid diacid analogs in lines 1 and 2 of figure106. They are not explicitly shown because it is obvious to one skilled in the art that these molecules are part of the invention.
  • Figures 107 through 1 15 and Figure 120 teach the synthesis of a new class of amines and aminoalcohols, as well as a range of derivatives that are suitable as buffers, monomers antimicrobials, and dispersants. Taught are secondary amino acids based on monochloroacetic acid and acrylic acid type monomers and their esters for both classes, sulfonates, phosphonates, alkoxylates, and polyamines based on acrylonitrile.
  • esters standard esters, phosphate esters, phosphonate esters, and sulfonate esters
  • these compounds that result from the reaction of alcohols or polyols are also within the scope of this invention, for linear, branched, saturated or unsaturated alcohols, including polyols such as, but not limited to, EG, PG, BG and polymers or block copolymers.
  • polyols such as, but not limited to, EG, PG, BG and polymers or block copolymers.
  • Figure 1 10 teaches the synthesis of primary diamines from gluteraldehyde and nitro compounds. The figure focuses on the monosubtitution of both of the primary amine groups., However, the invention includes the monosubstitution of just one amine, the disubstitution of both amines, and the disubstitution of one amine and monosubstitution of the other. Further, the invention includes the derivatives where one type of derivative is made on one amine, and another of the described derivative types is made on the other. Likewise, as shown in figure 93, the derivations can vary on the individual amine and still be within the scope of this invention.
  • Figure 1 1 1 is a continuation of Figure 1 10 in that it teaches more derivatives of the gluteraldehyde based diamines and dinitro compounds. Specifically, alkoxylation and acrylonitrile derivatives.
  • Figure 1 12 teaches the synthesis of a group of aminoalcohols based on glucose. While glucose is taught explicitly in this Figure, all aldehyde terminated sugars can be treated the same way as glucose to yield the analogous amines.
  • aldehyde terminated sugars included in this invention are allose, altrose, mannose, gulose, arabinose, xylose, fucose, idose, galactose, talose, ribose, arabinose, xylose, lyxose, erythrose, threose, glyceraldehyde, glycolaldehyde and the related lactic aldehyde.
  • flavoring aldehydes and fragrance aldehydes such as, but not limited to, vanalin,
  • the invention is not limited to the surfactants from the sugar aldehydes alone, but may be reacted with any of the aldehydes disclosed in this invention, as are the similar derivatives, such as the zwitterionics and phosphonates, which are also taught and within the scope of the invention.
  • the zwitterionic derivatives make very mild, high foaming surfactants that also hold promise as mineral collectors in mining, such as iron ore and other minerals. If D is -H, then a second substitution of the E containing hydroxyl moiety can be achieved, leading to the analogous surfactant with a generally more
  • Figure 1 13 expands on Figure 1 12 by teaching the acrylonitrile and alkoxylate derivatives. For the alkoxylation, the reaction can be significantly isolated to the primary amine group is shown in the first line, however, more aggressive reaction conditions will cause the hydroxyl groups to undergo alkoxylation as well. Leading to a mixture of products.
  • alkoxylators block coploymerize by reacting with one alkoxylating agent, such as EO, then another, such as PO or BO and repeat the process to achieve the desired HLB.
  • one alkoxylating agent such as EO
  • another such as PO or BO
  • This block copolymerization is within the scope of this invention for this and all alkoxylations taught.
  • the primary amine may be retained by performing the alkoxylation on the nitro compound that results in the first line of Figure 1 12. After the alkoxylation is complete, the nitro group can be retained, or reduced to the primary amine.
  • benzaldehyde and nitro compound amines Again, the alkoxylation can be done on the amine, and largely isolated to the amine, or under more aggressive conditions, on the hydroxyls as well. If alkoxylating the nitro compound, the alkoxylation will be isolated to the alcohol groups present. Reduction of the alkoxylated nitro compound will yield a primary amine. Due to the chiral nature of many of these molecules and their derivation from natural molecules, in addition to being excellent buffers, they are expected to be useful in pharmaceutical and other life science applications as part of drug delivery systems, and some, as therapeutic agents themselves.
  • Figure 1 15 is a continuation of Figure 1 14 and teaches the acrylonitrile derivatives.
  • the acrylonitrile addition can be isolated to the primary amine, mono (shown) or disubstituted, or under more aggressive conditions, also react with any hydroxyls present.
  • the resulting nitrile compounds can readily be reduced to their amine counterparts. Reacting the nitro compound, will result in the hydroxyls being substituted, which can then be reduced, along with the nitro group, which will produce in high yield primary amines and minimal secondary amine formation.
  • These amines can then undergo all the derivatives taught in this invention utilizing the aminoalcohols and are part of this invention.
  • Figure 1 16 - 1 17 teach the synthesis of dimmers, trimers and polymers when at least two hydrogens are present on the nitro containing carbon, and how polymers may be produced.
  • polymerizartion is always a concern.
  • controlling the addition order, rate and temperature can prevent polymer formation.
  • Many of the methoxy containing products can be made by reacting the remaining hydrogen(s) with formaldehyde prior to the reduction to the amine, but using the nitroalcohol is preferred as it leads to much less polymer formation. Particularly in cases where the reaction conditions can not be well controlled.
  • the amines and polyamines taught in the figures are able to undergo all the derivations taught and are part of this invention.
  • Figure 1 18 teaches a novel route to primary amino acids of several types and their nitro precursors. Again, monosubstitution is taught, but the substitution can by di- or tri if sufficient hydrogens are present in the starting nitro compound.
  • the carboxcylic acid functional molecules and there salts show this property under a wide range of conditions.
  • the use of the molecules disclosed in this invention are also known to exhibit synergistic antimicrobial properties when used in combination with other known antimicrobials.
  • antimicrobials known to show synergy include, but are not limited to isothiazolinones, carbamates, formaldehyde condensates, formaldehyde donors, phenols, parabens, quaternary ammonium compounds, methylenes, metals and their organic salts, halogenated organics and inorganics, hexetidine, phthalates, sulfonamides and all other antimicrobials.
  • gas scrubbing amines for removal of acid gases such as C0 2 , H 2 S, CO and other acidic gases from industrial processes. They can be used alone, or in combination with other amines, solvents, and all other known means of removing acid gases.
  • Adjuvents that are expected to increase the efficacy, weather used alone or in combinations that may include other surfactants, solvents, or coupling agents include alcohols, amines, ethyleneamines, alkoxylated amines, alkoxylated alcohols, ether amines, alkoxylated etheramines, taurates, sarcosinates, polyethylene glycol, polypropylene glycol, EO/PO block polymers and other non-ionic surfactants, particularly the broad class of alkoxylates. It is also expected that the molecules taught will be tolerated by glyphosate tolerant crops.

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  • Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention concerne des amines et des dérivés d'amines qui améliorent la plage de tamponnage et/ou réduisent la chélation et autres interactions négatives du tampon et du système à tamponner. La réaction d'amines ou de polyamines avec diverses molécules pour former des polyamines avec différents pKa étendra la plage de tamponnage. Des dérivés qui conduisent à des polyamines qui ont le même pKa fournissent une capacité de tamponnage supérieure. Des dérivés qui conduisent à des tampons zwitterioniques améliorent le rendement en permettant une plus grande plage de stabilité.
PCT/US2012/056190 2011-10-06 2012-09-20 Tampons biologiques ayant de larges plages de tamponnage WO2013052279A2 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US13/267,440 2011-10-06
US13/267,440 US8519141B2 (en) 2008-04-17 2011-10-06 Biological buffers with wide buffering ranges
US13/588,530 2012-08-17
US13/588,530 US8822728B2 (en) 2008-04-17 2012-08-17 Biological buffers with wide buffering ranges

Publications (2)

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WO2013052279A2 true WO2013052279A2 (fr) 2013-04-11
WO2013052279A3 WO2013052279A3 (fr) 2013-06-13

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS50149706A (fr) * 1974-05-21 1975-12-01
EP0317542A2 (fr) * 1987-11-13 1989-05-24 The Procter & Gamble Company Composition de nettoyage pour surfaces dures contenant des dérivés de l'acide iminodiacétique
US6331648B1 (en) * 1999-12-13 2001-12-18 Nova Molecular Technologies Inc Ether amines and derivatives
WO2009137765A1 (fr) * 2008-05-09 2009-11-12 Thomas Daly Tampons biologiques à larges spectres d’action

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS50149706A (fr) * 1974-05-21 1975-12-01
EP0317542A2 (fr) * 1987-11-13 1989-05-24 The Procter & Gamble Company Composition de nettoyage pour surfaces dures contenant des dérivés de l'acide iminodiacétique
US6331648B1 (en) * 1999-12-13 2001-12-18 Nova Molecular Technologies Inc Ether amines and derivatives
WO2009137765A1 (fr) * 2008-05-09 2009-11-12 Thomas Daly Tampons biologiques à larges spectres d’action

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